Virtual Library

Start Your Search

Marina Chiara Garassino



Author of

  • +

    MA03 - Clinomics and Genomics (ID 119)

    • Event: WCLC 2019
    • Type: Mini Oral Session
    • Track: Advanced NSCLC
    • Presentations: 1
    • Now Available
    • +

      MA03.10 - Prospective Evaluation of a Prognostic Clinico-Molecular Score (DEMo) to Predict Outcome of Advanced NSCLC Patients Treated with Immunotherapy (Now Available) (ID 1378)

      10:30 - 12:00  |  Author(s): Marina Chiara Garassino

      • Abstract
      • Presentation
      • Slides

      Background

      We have already reported three different molecular (MSC: plasma miRNA-signature classifier, Boeri, Clin Cancer Res 2019) and clinico-biochemical scores (DiMaio: Di Maio, EJC 2010; EPSILoN: Ann.Onco 2018 supp) able to differently predict prognosis in advanced non-small cell lung cancer (aNSCLC) patients treated with immunotherapy (IO). Exploiting the ability of each test we developed a combined clinico-biological composite score called DEMo (DiMaio EPSILoN MSC). Objective of the study is to prospectively evaluate the prognostic value of DEMo in aNSCLC patients treated with IO.

      Method

      We enrolled 127 consecutive aNSCLC patients treated with IO in first (n=37) and further-lines (n=90) at Istituto Nazionale dei Tumori, Milan. All patients had complete clinico-laboratoristic data necessary for both scores: DiMaio (ECOG-PS, sex, histology, stage, uses of platinum-based therapy at first-line and response to first-line) and EPSILoN (ECOG-PS, Smoke, Liver, LDH, NLRatio). MSC was prospectively evaluated in plasma samples collected prior starting IO and the risk level were assessed. Progression-free survival (PFS) and overall survival (OS) in strata of MSC/DiMaio/EPSILoN alone or DEMo and overall response rate (ORR), were considered as endpoints. Kaplan Meier were used to generate survival curves and Cox hazard model were employed to perform multivariate analyses.

      Result

      In multivariate analyses, adjusted for age, sex, pack/year and ECOG-PS, patients with high MSC and high DiMaio and EPSILoN scores reported a lower PFS (MSC: HR 1.72 CI95% 1.06 – 2.77, p=0.027; DiMaio: HR 2.63 CI95% 1.40 – 5.00, p=0.002; EPSILoN: HR 2.17 CI95% 1.16 – 4.16, p=0.014) and OS (MSC: HR 2.17 CI95% 1.29 – 3.70, p=0.003; DiMaio: HR 3.57 CI95% 1.66 – 7.69, p=0.001; EPSILoN: HR 2.50 CI95% 1.15 – 5.26, p=0.020). DEMo stratified patients into four risk groups according to the presence of 3–2–1–0 bad markers (High MSC/DiMaio/EPSILoN or none). Groups had 0%–0%–32.2%–53.3% 1-year PFS (p<0.0001) and 4.4%– 19.4% – 66.9% – 75.4% 1-year OS (p<0.0001). We further compared 0/1 to 2/3 combined groups. At the multivariate Cox model group 2/3 had a mPFS 1.9 vs 9.4 mo compared to group 0/1 (HR 3.70 CI95% 2.08 – 6.67, p<0.0001) and mOS 4.1 vs 22.4 mo (HR 4.76 CI95% 2.56 – 9.10, p<0.0001). Regarding ORR, DEMo group 0/1 had a 3.86 (CI95% 1.76-8.47) fold higher probability to respond compare to 2/3 group (p=0.0007).

      Conclusion

      DEMo composite biomarker is able to predict better prognosis compared to each single score and can be a useful tool for guiding IO treatment choices. In particular, DEMo allowed a good selection for those patients who are less likely to benefit from IO.

      Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.

      Only Active Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login or select "Add to Cart" and proceed to checkout.

  • +

    MA07 - Clinical Questions and Potential Blood Markers for Immunotherapy (ID 125)

    • Event: WCLC 2019
    • Type: Mini Oral Session
    • Track: Immuno-oncology
    • Presentations: 1
    • Now Available
    • +

      MA07.03 - A Circulating MicroRNAs-Based Test as Biomarker of Primary and Secondary Resistance in PD-L1 ≥50% NSCLC Treated with Immunotherapy (Now Available) (ID 2495)

      13:30 - 15:00  |  Author(s): Marina Chiara Garassino

      • Abstract
      • Presentation
      • Slides

      Background

      PD-L1 represents the only clinically approved biomarker to select patients for immunotherapy. However, about 20-25% of PD-L1≥50% NSCLC patients do not benefit of ICIs treatment. We showed that a plasma microRNA signature classifier (MSC), reflecting the switch towards an immunosuppressive profile of immune cells, identifies NSCLC patients with worse prognosis after ICIs, irrespective from PD-L1 expression. Aim of this trial is to prospectively define the MSC role as biomarker of primary or secondary resistance in PD-L1≥50% NSCLC treated with ICIs.

      Method

      Fifty consecutive advanced NSCLC patients with PD-L1≥50% treated with ICI as first (n=32) or further line were enrolled. Plasma samples, as well as demographics information, smoking history and ECOG PS were collected before starting ICI treatment. The MSC test identified patients at high (H) risk vs intermediate/low (I/L) risk levels. According to RECIST 1.1 criteria, patients were classified as responders (R), patients with stable disease (SD), and progressors (P). Objective Response Rate (ORR), Progression Free Survival (PFS) and Overall Survival (OS) in MSC risk level strata at the baseline were considered as endpoints. For 26 R or SD patients with extended follow-up, additive, not mandatory plasma samples were collected and analyzed at the time of revaluations. To determine changes in the risk level during follow-up, we evaluated changes in the probability of having progressive disease after two consecutive MSC tests, considering all possible combinations.

      Result

      Overall 17 (34%) R, 17 (34%) patients with SD, 11 (22%) P and 5 (10%) not evaluable patients were identified. Considering the baseline blood samples 11 (22%) NSCLC patients were MSC H. ORR was 0% in MSC H vs 45% for other patients (p=0.0090). Median PFS was 2.3 months for MSC H vs 10.9 months for other patients (HR=0.38; 95%CI=0.17-0.84; p=0.0174). Median OS was 2.9 months for MSC H vs 22.0 months for other patients (HR=0.18; 95%CI=0.07-0.47; p=0.0004). Data remained significant adjusting for age, sex, pack-years and ECOG performance status: PFS HR=0.31 (95%CI=0.13-0.73; p=0.0072) and OS HR=0.13 (95%CI=0.04-0.39; p=0.0003). Among the 26 patients with longitudinal evaluation of MSC risk level, all the 12 patients reaching progression during treatment showed an increase in the risk level (Sign-test p-value=0.0039). Conversely, when considering the 14 NSCLC patients still maintaining SD or responding to ICIs at the time of the analysis, the risk level decreased for 9 (64%) of them (Sign-test p-value=0.1655).

      Conclusion

      These preliminary results suggest that MSC risk level at the baseline and during treatment could help to identify primary or secondary resistance in PD-L1≥50% NSCLC patients treated with ICIs. Ongoing clinical trials are validating these results.

      Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.

      Only Active Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login or select "Add to Cart" and proceed to checkout.

  • +

    MA25 - Precision Medicine in Advanced NSCLC (ID 352)

    • Event: WCLC 2019
    • Type: Mini Oral Session
    • Track: Advanced NSCLC
    • Presentations: 1
    • Now Available
    • +

      MA25.01 - Pembrolizumab Plus Chemotherapy for Advanced NSCLC Without Tumor PD-L1 Expression: Pooled Analysis of KN021G, KN189 and KN407 (Now Available) (ID 1399)

      14:30 - 16:00  |  Author(s): Marina Chiara Garassino

      • Abstract
      • Presentation
      • Slides

      Background

      Randomized studies have demonstrated that pembrolizumab plus chemotherapy improves OS, PFS, and ORR compared with chemotherapy alone in patients with advanced NSCLC regardless of tumor PD-L1 expression level. We present a post hoc pooled analysis of pembrolizumab plus chemotherapy versus chemotherapy alone in patients with advanced NSCLC and no PD-L1 expression (ie, TPS <1%), representing an area of unmet need.

      Method

      Patients enrolled in KEYNOTE-021 cohort G (nonsquamous; NCT02039674), KEYNOTE-189 (nonsquamous; NCT02578680), and KEYNOTE-407 (squamous; NCT02775435) were included. Patients with nonsquamous NSCLC were randomized to pemetrexed-platinum with or without pembrolizumab; those with squamous NSCLC were randomized to carboplatin-paclitaxel/nab-paclitaxel with or without pembrolizumab. OS, PFS, and ORR were evaluated for the pooled intent-to-treat population. Response was assessed per RECIST v1.1 by blinded independent central review. Across studies, PD-L1 expression was assessed centrally using PD-L1 IHC 22C3 pharmDx assay (Agilent Technologies, Carpinteria, CA). Analyses were descriptive.

      Result

      Of 1298 patients enrolled across the 3 trials, 428 (33%) had PD-L1 TPS <1% (pembrolizumab plus chemotherapy, n=243; chemotherapy alone, n=185) and were included in this analysis. 52% had nonsquamous histology, 63% had ECOG PS of 1. Median (range) follow-up at data cutoff was 10.2 (0.1‒34.9) months. OS, PFS, and ORR were improved with pembrolizumab plus chemotherapy versus chemotherapy alone (Table). Grade ≥3 AEs (all-cause) occurred in 68% of patients receiving pembrolizumab plus chemotherapy versus 72% receiving chemotherapy alone. Immune-mediated AEs and infusion reactions occurred in 26% who received pembrolizumab plus chemotherapy versus 12% who received chemotherapy alone.

      Pembrolizumab + Chemotherapy

      n=243

      Chemotherapy
      Alone

      n=185

      Median (95% CI) OS, mo

      19.0 (15.2–24.0)

      11.0 (9.2–13.5)

      Hazard ratio (95% CI)

      0.56 (0.43–0.73)

      Median (95% CI) PFS, mo

      6.5 (6.2–8.5)

      5.4 (4.7–6.2)

      Hazard ratio (95% CI)

      0.67 (0.54–0.84)

      ORR, % (95% CI)

      46.9% (40.5%–53.4%)

      28.6% (22.3%–35.7%)

      Difference (95% CI)

      18.3% (9.0%–27.1%)

      Conclusion

      Our results highlight the clinically meaningful efficacy benefit and acceptable safety profile of pembrolizumab plus chemotherapy versus chemotherapy alone in patients with advanced NSCLC and no PD-L1 expression. Benefit was consistent with that observed in the overall study populations, suggesting pembrolizumab plus chemotherapy should be considered standard-of-care first-line therapy for all patients with NSCLC, irrespective of PD-L1 expression.

      Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.

      Only Active Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login or select "Add to Cart" and proceed to checkout.

  • +

    OA04 - Immuno Combinations and the Role of TMB (ID 126)

    • Event: WCLC 2019
    • Type: Oral Session
    • Track: Immuno-oncology
    • Presentations: 1
    • Now Available
    • +

      OA04.06 - Evaluation of TMB in KEYNOTE-189: Pembrolizumab Plus Chemotherapy vs Placebo Plus Chemotherapy for Nonsquamous NSCLC (Now Available) (ID 1936)

      15:15 - 16:45  |  Presenting Author(s): Marina Chiara Garassino

      • Abstract
      • Presentation
      • Slides

      Background

      First-line pembrolizumab plus chemotherapy with pemetrexed and platinum significantly improved OS (HR 0.49, P < .001), PFS (HR 0.52, P < .001) and ORR (47.6% vs 18.9%, P < .001) vs placebo plus chemotherapy with pemetrexed and platinum for metastatic nonsquamous NSCLC in the double-blind phase 3 KEYNOTE-189 study (NCT02578680); benefit was observed in all analyzed subgroups, including PD-L1 TPS <1%, 1-49%, and ≥50%. We explored the association of TMB with efficacy in KEYNOTE-189.

      Method

      616 patients were randomized 2:1 to pembrolizumab plus chemotherapy or placebo plus chemotherapy. TMB was determined by whole-exome sequencing of tumor and matched normal DNA. Association of TMB (continuous log10 transformed) with outcomes in each arm was assessed using Cox proportional hazards models (OS, PFS) and logistic regression (ORR); statistical significance was determined at the 0.05 level without multiplicity adjustment. The clinical utility of TMB on outcomes was assessed using prespecified TMB cutpoints of 175 and 150 Mut/exome (~13 and ~10 Mut/Mb by FoundationOne CDx). Data cutoff was 21 Sep 2018.

      Result

      293 (48.3%) treated patients had evaluable TMB data: 207 for pembrolizumab plus chemotherapy, 86 for placebo plus chemotherapy. Baseline characteristics and outcomes were generally similar in the TMB-evaluable and total populations. TMB as a continuous variable was not significantly associated with OS, PFS, or ORR for pembrolizumab plus chemotherapy (one-sided P = .174, .075 and .072, respectively) or placebo plus chemotherapy (two-sided P = .856, .055 and .434, respectively). Pembrolizumab plus chemotherapy improved OS, PFS, and ORR for TMB ≥175 and <175 (Table). Results were similar for TMB ≥150 and <150.

      Conclusion

      TMB was not significantly associated with efficacy of pembrolizumab plus chemotherapy or placebo plus chemotherapy as first-line therapy for metastatic nonsquamous NSCLC. Pembrolizumab plus chemotherapy had a similar OS benefit in the TMB-high and low subgroups.

      TMB ≥175 TMB <175

      Pembrolizumab plus Chemotherapy

      n = 100

      Placebo plus Chemotherapy

      n = 34

      Pembrolizumab plus Chemotherapy

      n = 107

      Placebo plus Chemotherapy

      n = 52
      Median OS (95% CI), mo 23.5
      (20.2-NE)
      13.5
      (7.0-NE)
      20.2
      (15.8-NE)
      9.9
      (7.4-19.1)
      HR (95% CI) 0.64 (0.38-1.07) 0.64 (0.42-0.97)
      Median PFS (95% CI), mo 9.2
      (7.6-14.0)
      4.7
      (4.0-5.5)
      9.0
      (6.7-11.1)
      4.8
      (4.5-6.6)
      HR (95% CI) 0.32 (0.21-0.51) 0.51 (0.35-0.74)
      ORR, % (95% CI) 50.0
      (39.8-60.2)
      11.8
      (3.3-27.5)
      40.2
      (30.8-50.1)
      19.2
      (9.6-32.5)

      Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.

      Only Active Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login or select "Add to Cart" and proceed to checkout.

  • +

    OA14 - Update of Phase 3 Trials and the Role of HPD (ID 148)

    • Event: WCLC 2019
    • Type: Oral Session
    • Track: Immuno-oncology
    • Presentations: 2
    • Now Available
    • +

      OA14.04 - Five-Year Outcomes From the Randomized, Phase 3 Trials CheckMate 017/057: Nivolumab vs Docetaxel in Previously Treated NSCLC (ID 894)

      11:30 - 13:00  |  Author(s): Marina Chiara Garassino

      • Abstract
      • Slides

      Background

      Historically, outcomes for advanced non-small cell lung cancer (NSCLC) have been poor, with 5-year survival rates < 5% with conventional chemotherapy. Nivolumab, a programmed death-1 (PD-1) inhibitor, was approved in 2015 for patients with previously treated advanced NSCLC based on two randomized phase 3 trials, CheckMate 017 (NCT01642004; squamous) and CheckMate 057 (NCT01673867; non-squamous), which demonstrated improved overall survival (OS) vs docetaxel. We report 5-year pooled efficacy and safety from these trials, representing the longest survival follow-up for randomized phase 3 trials of an immune checkpoint inhibitor in advanced NSCLC.

      Method

      Patients (N = 854; CheckMate 017/057 pooled) with advanced NSCLC, ECOG performance status (PS) ≤ 1, and progression during or after first-line platinum-based chemotherapy, were randomized 1:1 to nivolumab 3 mg/kg Q2W or docetaxel 75 mg/m2 Q3W until progression or unacceptable toxicity. After completion of the primary analyses, patients in the docetaxel arm no longer receiving benefit could cross over to receive nivolumab. OS was the primary endpoint for both studies.

      Result

      At 5-year follow-up, 50 nivolumab patients and 9 docetaxel patients were alive. Baseline characteristics of 5-year survivors in both arms were similar to the overall population and patients who survived < 1 year, except for a higher percentage of patients with ECOG PS 0 or tumor programmed death ligand-1 (PD-L1) expression ≥ 1% on nivolumab and ECOG PS 0 and Stage IIIB NSCLC on docetaxel. Nivolumab continued to show long-term OS and progression-free survival (PFS) benefit vs docetaxel with 5-year OS rates 13% vs 3% (HR, 0.68 [95% CI, 0.59–0.78]) and PFS rates 8% vs 0% (0.79 [0.68–0.92]). OS benefit with nivolumab vs docetaxel was observed across subgroups including patients with tumor PD-L1 expression < 1%, baseline liver and adrenal metastases, neutrophil-to-lymphocyte ratio < median, lactate dehydrogenase ≥ upper limit of normal or no baseline proton-pump inhibitor use. Among patients with an objective response to nivolumab (20%) or docetaxel (11%), 32% remained in response at 5 years vs none on docetaxel, with a median duration of response of 19.9 vs 5.6 months, respectively. Of the 5-year nivolumab vs docetaxel survivors, 36% vs 0% were on study drug, 20% vs 67% received subsequent immunotherapy (on or off study), and 10% vs 0% were off study drug, progression free, with no subsequent therapy. No new safety signals were observed with longer follow-up. Between 3 and 5 years’ follow-up, 8 of the 31 (26%) nivolumab-treated patients reported a treatment-related adverse event, 1 (3%) grade 3–4. The most common select adverse events (events with a potential immunological cause) were related to skin, in 4 (13%) patients, none of which were grade 3–4.

      Conclusion

      CheckMate 017 and 057 are the first phase 3 trials to report 5-year outcomes for a PD-1 inhibitor in previously treated advanced NSCLC, demonstrating a greater than 4-fold increase in 5-year OS rates with nivolumab (13%) over docetaxel (3%). Nivolumab remained well tolerated with no new safety signals.

      Only Active Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login or select "Add to Cart" and proceed to checkout.

    • +

      OA14.06 - Hyperprogressive Disease in Advanced Non–Small Cell Lung Cancer Patients Treated with Immune Checkpoint Inhibitors (Now Available) (ID 1835)

      11:30 - 13:00  |  Author(s): Marina Chiara Garassino

      • Abstract
      • Presentation
      • Slides

      Background

      Hyperprogressive disease (HPD) is a paradoxical boost in tumour growth described in a subset of cancer patients treated with immune checkpoint inhibitors (ICIs).

      Method

      We retrospectively collected data about all consecutive patients with advanced Non-Small Cell Lung Cancer (aNSCLC) treated with ICIs at our Institution between 04/2013 and 12/2018. Patients were classified according to our previously published clinical/radiological criteria for HPD (Lo Russo G, Clin Canc Res 2018). (Table). All ICIs administered for ≥1 cycle were admitted. Chi-square test was used to compare qualitative variables. Survival was estimated with Kaplan-Meier method. Log-rank test was used to compare curves. Multivariate analyses were performed with Cox hazard model.

      Table HPD definition on the basis of 3 concomitant out of the five possible criteria

      HPD CLINICAL & RADIOLOGICAL CRITERIA

      Time-to-treatment failure < 2 months

      Increase of ≥ 50% in the sum of target lesions major diameters between baseline and first radiological evaluation

      Appearance of at least two new lesions in an organ already involved between baseline and first radiological evaluation

      Spread of the disease to a new organ between baseline and first radiological evaluation

      Clinical deterioration with decrease in ECOG performance status ≥ 2 during the first 2 months of treatment

      Result

      We reviewed 301 cases and 257 were evaluable for response. We identified four categories: responders (R, 57 cases, 22.2%), patients with stable disease as best response (SD, 69 cases, 26.8%), patients with progressive disease as best response (P, 78 cases, 30.4%) and patients with HPD (53 cases, 20.6%). Clinical/pathological variables were uniformly distributed among groups, except for a higher rate of patients with Eastern Cooperative Oncology Group Performance Status (ECOG-PS) >1 in HPD group (p = 0.0141). After a median follow-up of 23.49 months (IQR 10.72–44.21 months), median Progression-Free Survival (mPFS) and median Overall Survival (mOS) were 14,2 vs 6,5 vs 2,3 vs 1,5 months ( p < 0.0001) and 32,5 vs 17,8 vs 7,8 vs 4,1months (p < 0.0001) in R, SD, P and HPD group, respectively. The multivariate analyses, between P and HPD groups, adjusted for ICIs line, number of metastatic sites and ECOG-PS according to PFS (HR 2.448, 95% CI 2.137-2.899, p<0.0001) and OS (HR 2.481, 95%CI 2.092-2.950, p < 0.0001) confirmed the worse outcome of HPD group.

      Conclusion

      Our updated analysis confirmed patients with HPD as a distinct category that performs significantly worse than other groups, including P patients. The incidence of HPD in our cohort is relevant. The ICIs’ detrimental effect has to be taken into account and further investigated.

      Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.

      Only Active Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login or select "Add to Cart" and proceed to checkout.

  • +

    P1.01 - Advanced NSCLC (ID 158)

    • Event: WCLC 2019
    • Type: Poster Viewing in the Exhibit Hall
    • Track: Advanced NSCLC
    • Presentations: 3
    • Now Available
    • Moderators:
    • Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
    • +

      P1.01-108 - PACIFIC-6: A Phase II Study of Durvalumab Following Sequential Chemoradiotherapy in Patients with Stage III, Unresectable NSCLC (ID 2318)

      09:45 - 18:00  |  Presenting Author(s): Marina Chiara Garassino

      • Abstract
      • Slides

      Background

      Non-small cell lung cancer (NSCLC) represents 85% of all lung cancers, with ~30% of patients (pts) presenting with Stage III disease. Platinum-based chemoradiotherapy (CRT) has historically been the standard of care (SoC) in this setting, but with poor long-term outcomes. Durvalumab is a selective high-affinity, human IgG1 monoclonal antibody that blocks PD-L1 binding to PD-1 and CD80. The phase III PACIFIC trial assessed durvalumab vs placebo in pts with locally advanced, unresectable, Stage III NSCLC, who did not progress following ≥2 overlapping cycles of platinum-based concurrent CRT (cCRT) (Antonia et al, NEJM 2017; 2018). Significant improvements in progression-free survival (PFS) and overall survival (OS) were observed with durvalumab (HR for PFS, 0.52; 95% CI 0.42–0.65; P<0.001; HR for OS, 0.68; 99.73% CI 0.47–0.997; P=0.0025). This data, along with comparable safety profiles between durvalumab and placebo in PACIFIC, supports the PACIFIC regimen (durvalumab following cCRT) as the new SoC in this setting. However, a proportion of pts are ineligible for cCRT for various reasons, and receive sequential CRT (sCRT) instead. PACIFIC-6 (NCT03693300) will assess the safety, efficacy, and quality of life of durvalumab in NSCLC pts who have not progressed following platinum-based sCRT.

      Method

      PACIFIC-6 is a phase II, open-label, multi-centre study to be conducted in 6 countries across Europe and North America. Pts ≥18 years old, with histologically or cytologically documented Stage III, unresectable NSCLC who have not progressed following platinum-based sCRT, and are ECOG PS ≤2 are eligible for inclusion; enrolment is not restricted to a biomarker-defined population. Approximately 150 pts will receive durvalumab (1500 mg intravenously) every 4 weeks for 24 months or until disease progression. Pts will be divided into 2 cohorts according to PS status. Pts will be assessed every 12 weeks, until death, withdrawal of consent, or the end of the study. The primary objective is to assess the safety and tolerability of durvalumab, as defined by grade 3 and 4 treatment-related adverse events (TRAEs) occurring within 6 months from initiation of durvalumab. Secondary objectives include investigator-assessed efficacy measurements such as PFS, overall response rate, duration of response (according to RECIST v1.1), as well as OS, lung-cancer mortality, and further safety assessments of all AEs and serious AEs. Exploratory objectives include assessment of pt-reported symptoms and quality of life, as well as evaluation of the association of tumour-based biomarkers (including PD-L1 expression and tumour mutational burden) with efficacy. Recruitment is ongoing.

      Result

      Section not applicable

      Conclusion

      Section not applicable

      Only Active Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login or select "Add to Cart" and proceed to checkout.

    • +

      P1.01-110 - Novel Regimens Versus Standard-of-Care in NSCLC: A Phase II, Randomized, Open-Label, Platform Trial Using a Master Protocol (Now Available) (ID 2288)

      09:45 - 18:00  |  Author(s): Marina Chiara Garassino

      • Abstract
      • Slides

      Background

      Although non-small cell lung carcinoma (NSCLC) is intrinsically resistant to immunotherapy agents, a subset of tumors are susceptible to T cell-mediated antitumor effects. Treatment regimens combining agents that target different processes within the cancer immunity cycle have the potential to enhance response in relapsed or refractory NSCLC. GSK3359609 is a humanized IgG4 antibody with potent agonist activity against Inducible T cell Costimulator (ICOS) and no or low depleting effect on antibody-dependent cell-mediated cytotoxicity.

      Method

      This is a randomized, phase II, open-label, platform trial utilizing a master protocol in patients with advanced NSCLC who have progressed on initial PD1/PDL1-based immunotherapy and platinum-based chemotherapy. The trial will consist of several sub-studies, with each sub-study comparing novel combinations vs. current standard-of-care (SOC). No treatment crossover is allowed. Additional sub-studies may be added over time following protocol amendments. In the first sub-study, patients are centrally randomized by internet to SOC (docetaxel) or novel ICOS drug combination (NIDC) (GSK3359609 + docetaxel) in a 1:2 ratio, stratified by squamous versus non-squamous NSCLC and line of PD1/PDL1; randomization to SOC is minimized thereafter. Primary endpoint is overall survival (OS). Secondary endpoints are survival rate at 12 and 18 months; tumor response according to RECIST 1.1 and iRECIST criteria; pharmacokinetic parameters of the novel immunotherapy; and safety. Exploratory endpoints include tumor and blood-based biomarker evaluations such as tumor mutational burden and gene expression. Interim analysis of OS will be done after approximately 45 deaths in both study groups, with ≥18 deaths in the combination immunotherapy group; final analysis will be done after 85 deaths (35 in combination immunotherapy group). The study will employ a Bayesian decision-making framework based on predictive probability of observing a significant improvement in OS in a future phase III trial. A sample size of ≤70 participants in each combination immunotherapy group and ≥35 participants in the SOC group will provide ≥81% power with a type 1 error of ≤2.3% for each pairwise comparison.

      Sub-study 1 will compare the efficacy of GSK3359609 plus docetaxel versus docetaxel alone. At least 105 patients are expected to enroll. GSK3359609/docetaxel will be administered for ≤2 years or 35 visits, or until disease progression, death or unacceptable toxicity. Both drugs are given as an IV infusion (docetaxel 75mg/m2; GSK3359609 80 mg).

      Result

      Study enrollment has begun and the primary endpoint results of sub-study 1 are expected mid-2020.

      Conclusion

      The study will provide information on the efficacy of novel immunotherapies used in combination.

      GlaxoSmithKline (NCT03739710).

      Only Active Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login or select "Add to Cart" and proceed to checkout.

    • +

      P1.01-135 - Salvage Chemotherapy After Immunotherapy Failure in Non-Small-Cell Lung Cancer Patients (Now Available) (ID 2490)

      09:45 - 18:00  |  Author(s): Marina Chiara Garassino

      • Abstract
      • Slides

      Background

      Objective response rate (ORR) to salvage chemotherapy (sCT) in non-small-cell lung cancer (NSCLC) patients failing upfront platinum-based doublets is limited (≈5-15%). Recently, unexpected favorable outcomes have been reported for sCT upon progression to immune checkpoint inhibitors (ICIs) as compared to historical data, with ORR observed in up to 53% and 27% in Asian and Caucasian patients respectively. Few data are available regarding prior response to ICIs and sCT performance, especially in Caucasian patients.

      Method

      All consecutive patients with advanced NSCLC who started ICIs at our institution from Apr 2013 to Dec 2018 were retrospectively reviewed. Patients who underwent sCT after progression to ICIs and had at least one radiological response assessment were included. ORR was calculated as the percentage of complete or partial responses according to RECIST 1.1 as best response. Survivals were estimated with Kaplan-Meier method. Correlation was assessed using Spearman’s test.

      Result

      Out of 283 patients included, 43 received sCT after ICIs. Among them, 29 (67%) had adenocarcinoma and 14 (37%) squamous cell carcinoma. 11 (26%) patients received sCT as second line therapy and 32 (74%) as third or more advanced treatment. sCT regimens included platinum based doublets (14; 32.5%), docetaxel or paclitaxel (20; 46.5%), and other monotherapies such as gemcitabine or vinorelbine (9; 21%). ORR to sCT was 30%. Median progression free survival and overall survival were 3.6 and 8.4 months, respectively. All patients receiving taxanes as sCT had already been treated with platinum based therapy and their ORR to sCT was 40%. ORR to upfront chemotherapy was 50%, while ORR to the last chemotherapeutic regimen prior to ICIs was 35%. ORR to sCT in pretreated patients was non-inferior to that observed in chemo-naïve ones (31% and 27%, respectively). High ORR (25%) was observed even in patients receiving sCT beyond third line. Neither response to ICIs (P=0.36) nor to prior chemotherapeutic regimens (P>0.05) were associated to the likelihood of achieving tumor response to sCT.

      Conclusion

      We provide further evidence that NSCLC patients progressing to ICIs might still benefit from sCT even if heavily pretreated, regardless of sensitivity to ICIs or previous chemotherapy regimens. Further investigations are needed for uncovering bases of increased sensitivity to genotoxic agents in patients with innate or acquired resistance to ICIs and exploiting optimal treatment sequence.

      Only Active Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login or select "Add to Cart" and proceed to checkout.

  • +

    P1.04 - Immuno-oncology (ID 164)

    • Event: WCLC 2019
    • Type: Poster Viewing in the Exhibit Hall
    • Track: Immuno-oncology
    • Presentations: 1
    • Now Available
    • Moderators:
    • Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
    • +

      P1.04-38 - Efficacy and Safety of Immunotherapy in Elderly Patients with Non-Small Cell Lung Cancer (Now Available) (ID 1383)

      09:45 - 18:00  |  Author(s): Marina Chiara Garassino

      • Abstract
      • Slides

      Background

      Most trials with Immune Checkpoint Inhibitors (ICIs) for Non-Small Cell Lung Cancer (NSCLC) included only small subgroups of patients (pts) aged ≥65. As NSCLC is often diagnosed in pts aged ≥70, real-world data about efficacy and safety of IO in elderly pts are essential.

      Method

      We retrospectively collected data about all pts with advanced NSCLC treated with IO at our Institution between April 2013 and March 2019. All ICIs administered for ≥1 cycle were admitted. Pts were stratified for age as follows: <70 year-old (yo), 70-79 yo, ≥80 yo. Chi-square test was used to compare qualitative variables. Survival was estimated with Kaplan-Meier method. Log-rank test was used to compare curves. Multivariate analyses were performed with Cox model.

      Result

      We reviewed 290 cases, with a median age of 67 (range: 29-89). Pts aged<70, 70-79 and ≥80 yo were 180, 94 and 16, respectively. Two hundred five pts received an anti-PD1, 77 an anti-PDL1, 8 an anti-CTLA4 or a combo-IO. Clinical/pathological variables were uniformly distributed across age classes, except for a higher rate of males (p 0.0228) and squamous histology (p 0.0071) in the intermediate class. Response Rate (RR) was similar across age groups (21.5% vs 22.3% vs 18.8% for pts aged<70 vs 70-79 vs ≥80 yo, respectively; p 0.9470). Median PFS did not differ according to age (2.8 vs 3.5 vs 2.6 mos for pts aged<70 vs 70-79 vs ≥80 yo, respectively; p 0.2020). Similarly, median OS was similar across age classes (9.1 vs 11.3 vs 9.6 mos for pts aged<70 vs 70-79 vs ≥80 yo, respectively; p 0.9144). These results did not change after stratification for sex (p 0.516 for PFS, p 0.5154 for OS) and histology (p 0.9057 for PFS, p 0.1002 for OS). The incidence of toxicity was comparable across subgroups (grade ≥2 adverse events in 35.8% vs 32.7% vs 37.5% for pts aged<70 vs 70-79 vs ≥80 yo, p 0.6493). The only variables influencing outcome at both univariate and multivariate analyses were performance status (p<0.0001 for PFS, p 0.0192 for OS), number of metastatic sites (p 0.0842 for PFS, p 0.0235 for OS) and IO line (p<0.0001 for both PFS and OS), regardless age group.

      Conclusion

      Advanced age is apparently not associated to a reduced efficacy of IO in our case series. Furthermore, no toxicity concern emerges even among the eldest pts. Therefore, to our opinion ICIs should be considered irrespective of age, provided an optimal PS at baseline. Of note, IO is often the only therapeutic option applicable to these cases considering the toxicity of chemotherapy.

      Only Active Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login or select "Add to Cart" and proceed to checkout.

  • +

    P1.06 - Mesothelioma (ID 169)

    • Event: WCLC 2019
    • Type: Poster Viewing in the Exhibit Hall
    • Track: Mesothelioma
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
    • +

      P1.06-16 - Molecular Signature in Malignant Pleural Mesothelioma (MPM). Preliminary Data of Rames Study (ID 254)

      09:45 - 18:00  |  Author(s): Marina Chiara Garassino

      • Abstract

      Background

      MPM is an uncommon cancer with limited therapeutic options and poor clinical outcomes. The relative rarity of these tumor has limited the identification of MPM-driver molecular as well as the development of specific drugs

      Method

      RAMES study evaluated the second-line efficacy of gemcitabine/ramucirumab treatment vs. gemcitabine/placebo.

      From December 2016 to July 2018 (end of enrolment), 164 patients (pts) were admitted to this study.

      We evaluated by NGS the mutational profile of a panel of 34 genes (ACTB, ACTG1, ACTG2, ACTR1A, BAP1,CDH8, CDK4, CDKN2A, CDKN2B, COL3A1, COL5A2, CUL1, DHFR, GOT1, KDR, KIT, MXRA5, NF2, NFRKB, NKX6,-2, NOD2, PCBD2, PDZK1IP1, PIK3CA, PIK3CB, PSMD13, RAPGEF6, RDX, SETDB1, TAOK1, TP53,TXNRD1, UQCRC1, XRCC6).

      We reported the results of the first 87 pts (54%): hystotype was epithelioid in 70 pts (80%), biphasic in 14 pts (16%) and sarcomatoid in 3 pts (4%). Median age was 63 years (range 45-81). 70 pts were male (80%) and 17 pts were female (20%). In the present analysis, we included 55 pts in stage III (63%), 26 pts in stage IV (30%) and 6 pts whose stage was unknown. Median first-line PFS platinum/pemetrexed therapy was for 5.75 months (I.C. 95% 4.75-6.76). PFS was ≤6 months for 40 pts (49%), and 6 months for 41 pts (51%).

      Result

      187 functional somatic mutations were identified. Genomic alterations/patient were 1 gene in 29 pts (33%), 3 genes in 18 pts (21%) and ≥5 genes in 2 pts (2%). The most frequent somatic mutations were RDX in 35 pts (40%), MXRA5 in 20 pts (23%), BAP1 in 13 pts (15%) and ACTG 1 in 9 pts (11%). When patients were collated by stage, the most frequent mutations were: MXRA5 in 16 pts in stage III (29%), BAP1 in 5 pts in stage IV (19%) and RDX in 16 pts in stage IV (62%). The percentage of somatic mutations in patients with PFS as first-line chemotherapy for ≤6 and >6 months was 2.2 and 1.6 (p=0.032), respectively. The most frequent mutations/patient for ≤6 and >6 months PFS were: RDX in 14 pts (35%) with PFS < 6, RDX in 19 pts (46%) with PFS >6 and MXRA5 in 11 pts (27%) with PFS >6.

      Conclusion

      This preliminary data suggests a possible role that a genetic signature may play in distinguishing MPM with different clinical-pathological features. The results are expected to be clarified further in the second step of the study, which is ongoing.

  • +

    P1.16 - Treatment in the Real World - Support, Survivorship, Systems Research (ID 186)

    • Event: WCLC 2019
    • Type: Poster Viewing in the Exhibit Hall
    • Track: Treatment in the Real World - Support, Survivorship, Systems Research
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
    • +

      P1.16-09 - Post-Progression Outcomes After Pembrolizumab in Patients with NSCLC and High PD-L1 Expression: Real-World Data from a European Cohort (ID 2749)

      09:45 - 18:00  |  Author(s): Marina Chiara Garassino

      • Abstract

      Background

      Real-world data regarding treatment patterns and clinical outcomes after progression on first-line pembrolizumab (pembro) monotherapy among NSCLC patients are lacking.

      Method

      A comprehensive clinicopathological database of 173 consecutive patients with NSCLC and PD-L1>50% treated with first-line pembro in 14 centers in Italy, Spain, Greece and Switzerland was retrospectively created and post-progression patterns and outcomes were recorded. Analysis was performed using the SAS 9.3 software.

      Result

      Main clinicopathological features are summarized in Table 1. Median TPS score for PD-L1 expression was 70%. Median duration of pembro treatment was 6.1 months (range: 0.2-20.8). Thirty patients (17.4%) received pembro despite having non-metastatic disease (stage I-IIIC), as deemed medically inoperable or ineligible for definite chemo-radiotherapy. At data cut-off (10th April 2019), 100 patients (58%) had stopped treatment due to disease progression, 9 (5%) due to toxicity, 3 (2%) for other reasons and 61 (35%) were still on treatment. Best response to pembro was CR, PR, SD and PD in 2%, 34%, 20% and 24% respectively, while in 11.6% death occurred in the absence of documented PD. Among patients who progressed (N=100), in 18 cases pembro was continued beyond progression, as considered to confer clinical benefit. Among patients who discontinued pembro (N=94), 47% received any second-line chemotherapy and 53% received no further treatment. Main chemotherapy regimens were carboplatin with either pemetrexed (16%) or gemcitabine (9%) or paclitaxel (7%), cisplatin-pemetrexed (7%) and gemcitabine monotherapy (9%). Best response to chemotherapy was CR, PR, SD and PD in 2%, 30%, 11% and 32% respectively. After a median follow-up of 11.2 months, median OS was 13.5 months (range: 0.16-25.8+).

      Table 1: Main clinicopathological characteristics of the patient cohort.

      N=173

      %

      COUNTRY OF ORIGIN

      Italy

      98

      56.7

      Greece

      32

      18.5

      Switzerland

      27

      15.6

      Spain

      16

      9.2

      SEX

      Male

      112

      64.7

      Female

      61

      35.3

      AGE Median (Range) yrs

      68 (19-86)

      SMOKING STATUS

      Current

      66

      38.2

      Former

      86

      49.7

      Never

      18

      10.4

      Unknown

      3

      1,7

      PERFORMANCE STATUS

      0

      50

      28.9

      1

      80

      46.2

      2

      41

      23.7

      3

      2

      1.2

      HISTOLOGY

      Adeno

      116

      67.1

      Squamous

      37

      21.4

      Large Cell

      2

      1.2

      Pleiomorphic

      3

      1.7

      Sarcomatoid

      7

      4.0

      Poorly differentiated/

      Undifferentiated

      8

      4.6

      SITE OF METASTASIS

      Bone

      74

      49.7

      Intrapulmonary/Contralateral Lung

      72

      48.3

      Adrenal

      43

      28.9

      Brain

      30

      20.1

      Liver

      23

      15.4

      Other

      63

      36.4

      TNM STAGE AT DIAGNOSIS (AJCCC v.8)

      I

      2

      1.2

      II

      2

      1.2

      III

      26

      15.0

      IV

      142

      82.1

      Unknown

      1

      0.5

      STEROID USE

      Yes

      48

      27.7

      No

      105

      60.7

      Unknown

      20

      11.6

      Conclusion

      Real-world data in a large retrospective cohort, indirectly compared to Keynote 024, suggest that: 1) Due to it’s favorable toxicity profile, pembro is also an option in earlier stages in frail (PS=2 or medically inoperable stage I-III) patients, 2) One in five patients continues pembro beyond progression due to clinical benefit and 3) More than half of patients who progress do not receive any second-line treatment, mainly due to clinical deterioration.

  • +

    P2.09 - Pathology (ID 174)

    • Event: WCLC 2019
    • Type: Poster Viewing in the Exhibit Hall
    • Track: Pathology
    • Presentations: 1
    • Now Available
    • Moderators:
    • Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
    • +

      P2.09-05 - Clinical and Biological Characterization of Lung Enteric Adenocarcinoma (Now Available) (ID 1650)

      10:15 - 18:15  |  Author(s): Marina Chiara Garassino

      • Abstract
      • Slides

      Background

      Lung Enteric Adenocarcinoma (LEA) is a rare and poorly characterized variant of Lung Adenocarcinoma (LA), defined by an intestinal differentiation in ≥50% of tumor and ≥1 colorectal biomarker at Immunohistochemistry.

      Method

      We retrospectively identified the cases of LEA diagnosed at Fondazione IRCCS Istituto Nazionale dei Tumori (INT), Milan, Italy between 01/2013 and 12/2018. Next Generation Sequencing was performed with IonTorrent (ThermoFisher Scientific, Life Technologies) by using the commercial Hot Spot Cancer Panel (HCP) on DNA derived from formalin-fixed paraffin-embedded tissues. ALK and ROS-1 status was assessed with fluorescent in situ hybridization. PD-L1 expression was determined with DAKO22C3 assay. Biological data obtained from our cases were compared with those reported in Tumor Cancer Genome Atlas (TCGA) for LA, restricting the comparison only to the genes targeted by HCP.

      Result

      We identified 38 LEA cases. Main clinical and biological characteristics of the two populations are detailed in the table.

      Variable/

      gene mutation

      INT LEA (N=38)

      TCGA LA (N=660)

      %

      %

      Gender

      Female

      34.1

      51.9

      Male

      65.9

      47.9

      Unknown

      0

      0.2

      Smoking status

      Former/current

      76.3

      78.9

      Never

      15.8

      14.1

      Unknown

      7.9

      7.0

      Disease stage

      I

      2.6

      51.6

      II

      2.6

      23.0

      III

      28.9

      16.4

      IV

      65.9

      4.7

      Unknown

      0

      4.3

      TP53

      52.6

      54.1

      KRAS

      34.2

      32.4

      STK11

      23.7

      15.8

      CDKN2A

      15.8

      3.9

      APC

      7.9

      4.8

      CTNNB1

      7.9

      3.8

      EGFR

      7.9

      15.8

      KIT

      5.3

      2.1

      PI3KCA

      5.3

      5.9

      SMAD4

      5.3

      4.1

      ATM

      2.6

      8.9

      BRAF

      2.6

      8.2

      FGFR

      2.6

      0.8

      GNAS

      2.6

      3.8

      NRAS

      2.6

      0.6

      PDGFRA

      2.6

      7.4

      RB1

      2.6

      5.8

      SMO

      2.6

      2.7

      Neither ALK nor ROS-1 rearrangements were detected in our case series. PD-L1 was negative in 23 cases, 1-49% in 9 cases, not evaluable in 6 cases. Microsatellite were stable except for 3 cases with low instability and 3 not evaluable cases.

      Conclusion

      Our series of LEA was small and differed from TCGA LA for a higher proportions of males and metastatic disease. Given these limitations, our LEA genetic profile showed some difference from that of TCGA LA. In particular, LEA showed a higher incidence of STK11, CTNNB1, FGFR, NRAS, KIT and CDKN2A mutations, and a lower incidence of ATM, BRAF, PDGFRA, RB-1 and EGFR mutations. PD-L1 expression, ALK and ROS-1 rearrangements were lower than literature data in LA. Most cases were microsatellite stable. In conclusion, further research is needed to understand the biology of LEA, which seems partially different from common LA.

      Only Active Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login or select "Add to Cart" and proceed to checkout.

  • +

    PC04 - Is Chemotherapy Necessary for Advanced NSCLC Patients With PD-L1 50% or More? (ID 86)

    • Event: WCLC 2019
    • Type: Pro-Con Session
    • Track: Advanced NSCLC
    • Presentations: 1
    • Now Available
    • +

      PC04.01 - Pro: Chemotherapy Is Necessary (Now Available) (ID 3571)

      11:30 - 13:00  |  Presenting Author(s): Marina Chiara Garassino

      • Abstract
      • Presentation
      • Slides

      Abstract

      As first-line therapy single agent pembrolizumab showed better outcomes than chemotherapy (CT) in patients with NSCLC and PD-L1 expression ≥50% [1]. Recently has been published another phase 3 trial in which patients with aNSCLC with an expression of PD-L1 ≥1%, treated with pembrolizumab as single agent, results in better overall survival (OS) than CT in first-line, mainly in subgroup with PD-L1 ≥50% [2].

      After the approval and subsequent use of pembrolizumab as single agent in first-line in NSCLC with PD-L1 ≥50%, in 2018 several phase III trials explored the combination of immunotherapy agents (pembrolizumab and atezolizumab), with no regards of PD-L1 status, in association with standard CT, gaining better outcomes than CT alone in first-line NSCLC [3-8].

      A matter of debate is what we have to do in patients with PD-L1 ≥50% due to the absent comparison between combination therapy and ICI as single agent and similar results in 1-year OS among these treatments [1,3-4].

      So, why should we suggest the use of combination over ICIs as single agent in patients with PD-L1 ≥50% in first-line?

      First of all, we can see that trials of combination therapy report benefit with CT plus ICI across all PD-L1 subgroups, with a greater magnitude of benefit in patients with PD-L1 ≥50% with no regards of kind of drugs used (either CT and ICI) and histology (squamous or non-squamous) [3-8]. This magnitude of benefit is supported from an higher objective-response rate (ORR) in patients treated with combination therapy over ICI as single agent in subgroups of patients with PD-L1 ≥50% [1-4], suggesting combination therapy as best choice even in patients with highly symptomatic disease with the purpose of obtaining a fast shrinkage of tumor.

      Analyzing Kaplan-Meyer curves of single agent trials [1,2], you can observe that there is a violation of proportional hazard assumptions. We can see a crossing of the curves within first 3-6 months suggesting us that there’s a subgroup of patients who have a worse prognosis when treated with single agent immunotherapy over CT. This worse prognosis could be possibly partially due to a phenomenon called hyperprogressive disease [9], a quicken tumor growth during treatment with ICIs in NSCLC irrespectively of the line of therapy. If we look at Kaplan-Meyer curves of all combination studies, we can see that the combination of CT plus ICI abrogates the crossing curves [3,4,6,8], probably overcoming hyperprogessive disease with the addiction of CT by modulating tumor microenvironment.

      In subgroups of patients with liver and/or brain metastases, generally considered at worse prognosis, combination therapy demonstrates a benefit. In a retrospective analysis of KEYNOTE189 [10] were evaluated outcomes of patients with brain and/or liver metastases. In this analysis the addiction of pembrolizumab to CT grants a benefit over CT alone either in progression-free survival, OS and ORR in patients with liver and/or brain metastases. Another evidence of benefit in patients with liver metastases in combination therapy was seen in IMpower150, in which the addiction of atezolizumab to bevacizumab plus CT seemed to add something even though there’s a bias due to the use of bevacizumab [5].

      In advanced NSCLC treated with ICI as single agent [1,2] we see a lower benefit in non-smoker than in current or former smoker patients, whilst in combination studies this difference isn’t seen regardless kind of drug and histology [3,6-8].

      Even gender may be a possible reason to choose combination instead of ICI as single agent. As we previously do for smoking habit, we indirectly compare trials with single agent and with combination. We can see that in KEYNOTE024 there’s a stronger benefit using pembrolizumab in males over females. This reported benefit for male patients is lost in combination treatment, with slight better outcomes in women instead, with no regards of drugs used and histology [3,4,6-8].

      Finally, basing on preclinical evidences, we know that the combination between CT and ICIs may enhance the immune system activity due to immunological effect of cytotoxic agents through the expression of PD-L1 on the surface of tumor cells, the depletion of myeloid-derived suppressor cells and T-regulatory cells and the augmentation of the presentation of antigens by cancer cells [10].

      At the state of the art the aim of our discussion remains an unanswered question but based on what we previously said, at least in patients with high tumor burden, in never smokers, we suggest CT plus ICI as first-line in aNSCLC with PD-L1 ≥50%.This could allow us not to lose patients in the first six months of treatment.

      [1] Reck M et al.Pembrolizumab versus chemotherapy for PD-L1 positive non-small cell lung cancer. NEJM 2016; 375: 1822-1833

      [2] Mok TSK et al. Pembrolizumab versus chemotherapy for previously untreated , PD-L1 expressing, locally advanced or metastatic non-small cell lung cancer (KEYNOTE-042): a randomised, open-label, controlled, phase 3 trial. Lancet 2019; 393: 1819-1830

      [3] Gandhi L et al. Pembrolizumab plus chemotherapy in metastatic non-small cell lung cancer. NEJM 2018; 378: 2078-2092

      [4] Paz-Ares L et al. Pembrolizumab plus chemotherapy for squamous non-small-cell lung cancer. NEJM 2018; 379: 2040-2051

      [5] Socinski MA et al. Atezolizumab for first-line treatment of metastatic nonsquamous NSCLC. NEJM 2018; 378(24): 2288-2301

      [6] Cappuzzo F et al. IMpower130: efficacy and safety from a randomise phase 3 study of carboplatin and nab-paclitaxel with or without atezolizumab in 1L advanced non-squamous NSCLC. Presented at ESMO 2018

      [7] Jotte R et al. IMpower131: primary PFS and safety analysis of a randomized phase III study of atezolizumab + carboplatin + paclitaxel or nab-paclitaxel vs carboplatin + nab-paclitaxel as 1L therapy in advanced squamous NSCLC. Presented at ASCO 2018

      [8] Papadimitrakopoulou VA et al. IMpower132: PFS and safety results with 1L atezolizumab + carboplatin/cisplatin + pemetrexed in stage IV non-squamous NSCLC. Presented at WCLC 2019

      [9] Proto C et al. Choosing wisely first line immunotherapy in non-small cell lung cancer (NSCLC): what to add and what to leave out. Cancer Treat Rev 2019; 75:39-51

      [10] Garassino MC et al. Outcomes among patients with metastatic nonsquamous NSCLC with liver metastases or brain metastases treated with pembrolizumab plus pemetrexed-platinum: results from the KEYNOTE-189 study. Presented at AACR 2019

      Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.

      Only Active Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login or select "Add to Cart" and proceed to checkout.

  • +

    PR02 - Press Conference (ID 387)

    • Event: WCLC 2019
    • Type: Press Conference
    • Track: Immuno-oncology
    • Presentations: 1
    • Now Available
    • Moderators:
    • Coordinates: 9/08/2019, 09:45 - 10:30, CC7.1 A&B
    • +

      PR02.07 - Evaluation of TMB in KEYNOTE-189: Pembrolizumab Plus Chemotherapy vs Placebo Plus Chemotherapy for Nonsquamous NSCLC (Now Available) (ID 3609)

      09:45 - 10:30  |  Presenting Author(s): Marina Chiara Garassino

      • Abstract
      • Presentation
      • Slides

      Abstract not provided

      Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.

      Only Active Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login or select "Add to Cart" and proceed to checkout.