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Margarita Majem

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    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: 2
    • Now Available
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      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

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      PC04.02 - CON: ICI Is Enough (Now Available) (ID 3572)

      11:30 - 13:00  |  Presenting Author(s): Martin Reck

      • Abstract
      • Presentation
      • Slides

      Abstract

      The implementation of anti PD-1 / anti PD-L1 checkpoint inhibitors has completely changed management of patients with advanced non-small-cell lung cancer (NSCLC). On the way to an individualized use of these agents a correlation between the PD-L1 expression on tumor cells and immune cells and efficacy of immunotherapies could be demonstrated across different agents and treatment lines.

      In particular a clear correlation between survival and PD-L1 expression on tumor cells (TPS-score) has prospectively been evaluated and validated for the anti-PD1 antibody pembrolizumab defining a TPS score of =/> 50% as a predictor for enhanced outcome by pembrolizumab and showing impressive 4 and 5 year overall survival rates for untreated patients with a TPS-Score of =/> 50% of 48% and 29.6% respectively (1,2).

      Two prospectively randomized phase III trials confirmed the superior efficacy of pembrolizumab monotherapy with a significant prolongation of overall survival compared to platinum based chemotherapy in untreated patients with a TPS-score of =/> 50% (3,4).

      Recently the concept of combining immunotherapies with chemotherapies has demonstrated superior efficacy compared to chemotherapy patients with advanced NSCLC independent from the PD-L1 expression and the question appears, whether such a combination would also be the preferred treatment for the selected group of patients with a TPS-score of =/>50%.

      Analysing this question a couple of points need to be addressed:

      First of all this important question has never been addressed appropriately in a prospective trial and in none of the combination trials a immunotherapy monotherapy arm was part of investigated schedule. Therefore all assumptions remain subjective and exploratory.

      Second: We have seen a dramatic improvement of survival expectation together with a relevant prolongation of treatment duration by the adaption of immunotherapies in management of advanced NSCLC. Therefore tolerability, symptom control and quality of life become essential parameters for feasibility of treatment. Across all chemo-immunotherapy combination trials the frequency of CTC grade 3-5 treatment related adverse events (TRAEs) was substantially higher compared to the pembrolizumab monotherapy arms. In particular in an updated report of the Keynote 189 trial the frequency of TRAEs grade 3-5 was 71.9% for the combination of pembrolizumab and chemotherapy compared to 17.8% in the Keynote 42 trial and 31.2% in the Keynote 24 trial leading to a treatment discontinuation rate of 33.6% compared to 9% and 13.6% in the Keynote 42 and 24 trial (4,5,6).

      Considering the symptomatic efficacy ICI monotherapy has shown a clinical relevant improvement of symptoms during treatment compared to chemotherapy assessed by the QLA-C30 GHS/QOL score together with a substantial prolongation of time to symptom deterioration in the Keynote-24 (7). This unique pattern of symptomatic efficacy, which clearly reflects the patient related impact of anti tumor therapy has so far not been to that extent for the combination trials.

      Third: Besides the impressive activity demonstrated by the use of first line chemo-immunotherapy combinations we are confronted with the rapidly emerging clinical problem, that we suffering effective and tolerable post progression treatment opportunities. So far no specific treatment approaches are available and mostly we are ending up with the use of limited effective docetaxel +/- an antiangiogenic agent. In contrast a first line ICI monotherapy offers the opportunity of a post progression full dosed platinum based combination treatment with clearly higher efficacy compared to docetaxel alone.

      Fourth: Currently the most appropriate endpoint to assess efficacy of immunotherapies remains to be determined and we have seen in various trials that response and PFS might not be the optimal endpoints. In contrast it is general accepted the survival represents the most eminent and meaningful endpoint. Looking on the survival results of the different trials the differences in follow up periods need to be taken into account leading potential differences in the assessment of survival times. However respecting the lack of prospective randomised trials it appears that no benefit in survival in particular long term survival could be generated by the addition of chemotherapy to immunotherapy in the group of patients with a TPS-score =/> 50%. In an exploratory analysis of the Keynote 189 trial the 2 year OS rate for patients with a TPS-score =/> 50% was 51.9% for the combination of chemotherapy and pembrolizumab compared to 51.5% and 44.7% for pembrolizumab monotherapy in the Keynote-24 and -42 trial. Furthermore also the Hazard ratios were comparable across the trials (HR 0.59 for Keynote-189 compared to HR 0.63 and 0.69 in Keynote-24 and -42).

      In summary ICI monotherapy represents the preferred new highly effective and well tolerable first-line treatment opportunity in untreated patients with a TPS-score of =/> 50%. Addition of chemotherapy is associated with poorer tolerability and in particular long-term tolerability.

      Ongoing research might define the few patients, where tumor control cannot be achieved by ICI monotherapy.

      1. Garon EB, Rizvi NA, Rui R, et al: Pembrolizumab for the treatment of non-small-cell lung cancer. N Engl J Med 372 (2015): 2018-2018

      2. Garon EB, Hellmann MD, Rizvi NA et al: Five-Year Overall Survival for patients with advanced non-small-cell lung cancer treated with pembrolizumab: results from the phase I Keynote-001 studay. J Clin Oncol (2019): e-published June 2, 2019-06-01

      3. Reck M, Rodriguez-Abreu D, Robinson AG et al: Pembrolizumab versus chemotherapy for PD-L1 positive non-small-cell lung cancer. N Engl J Med (2016): 1823-1833.

      4. Mok TSK, Wu Y-L, Kudaba I 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): 1819-1830.

      5. Gadgeel S, Garrassino MC, Esteban E, et al: Keynote-189: Updated overall survival and progression after the next line of therapy with pembrolizumab plus chemotherapy with pemetrexed and platinum vs placebo plus chemotherapy for metastatic nonsquamous NSCLC: ASCO 2019, abstract 9013

      6. Reck M, Rodriguez-Abreu D, Robinson AC et al: Updated analysis of Keynote-024: Pembrolizumab vers platinum-based chemotherapy for advanced non-small-cell lung cancer with PD-L1 Tumor Poportion Score of 50% or greater: J Clin Oncol 37 (2019): 537-546

      7- Brahmer J, Radriguez-Abreu D, Robinson AG et al: Health-related quality-of-life results for pembrolizumab versus chemotherapy in advanced, PD-L1-positive NSCLC (Keynote-024): a multicentre, intenational, randomised, open-label phase 3 trial. Lancet Oncology 18 (2017): 1600-1609.

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Author of

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    EP1.16 - Treatment in the Real World - Support, Survivorship, Systems Research (ID 206)

    • Event: WCLC 2019
    • Type: E-Poster Viewing in the Exhibit Hall
    • Track: Treatment in the Real World - Support, Survivorship, Systems Research
    • Presentations: 1
    • Now Available
    • Moderators:
    • Coordinates: 9/08/2019, 08:00 - 18:00, Exhibit Hall
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      EP1.16-01 - A Spanish Initiative to Know the Unmet Needs of Women with Lung Cancer: "Circulos Program" (Now Available) (ID 1847)

      08:00 - 18:00  |  Author(s): Margarita Majem

      • Abstract
      • Slides

      Background

      The personal and family impact of an oncological disease can only be adequately understood and managed from a biopsychosocial perspective. Lung cancer experience has a profound impact on the well-being of both patient and family caregiver and is largely influenced by communication within the family environment. Lung cancer impact can be especially significant when women are affected.

      Method

      The objective of this study was to develop an informative program for women with lung cancer, implementing the development of strategies in order to get a deepening knowledge of their perceived needs. Additionally, we aimed to define and design new useful resources that may help other women with lung cancer. A qualitative research allowed to collect data on the experiences in the circle of women and their families, and the identification of the needs and the coping resources used of the participants. The collection of these data was what led to the development of the tools used to develop the support strategies.

      Result

      A total of 10 women with lung cancer from Galicia (Spain) participated in 7 sessions. At the personal and psychological level in the women circle, needs were related to improve medical information they get from their physicians, share information and experiences with women in the same situation, more holistic-human care, and the need for more supporting groups. About the social and labor environment, they expressed concern about the social stigma associated with lung cancer, and the culpability for having smoked as well as the concern related to the interruption of working life. The family environment also expressed the need for emotional support and preparation for families and caregivers to be able to support the patient, the need to provide them with strategies to improve the situation, and the need to overcome initial isolation through working groups. Regarding resources, women´s circle was mainly focused on occupying time with new activities, humor and not stigmatizing the disease and the professionals who assist them.

      Conclusion

      “Círculos program”, even being a pilot program, show the benefits of a more humane approach to the treatment of lung cancer in women, with a better understanding of patients and families needs. More similar programs should be done in order to improve the quality of life of these patients and their transit through this disease.

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    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
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      MA07.02 - Early Change of dNLR Is Correlated with Outcomes in Advanced NSCLC Patients Treated with Immunotherapy (Now Available) (ID 2676)

      13:30 - 15:00  |  Author(s): Margarita Majem

      • Abstract
      • Presentation
      • Slides

      Background

      The [neutrophils/[leucocytes-neutrophils] ratio (dNLR) correlates with immune checkpoint inhibitors (ICI) outcomes in advanced non-small cell lung cancer (aNSCLC) patients. Significance of early dNLR change after the first course of ICI is unknown.

      Method

      Patients with NSCLC treated with ICI (PD(L)1+/-CTLA4) between Nov. 2012 and Jun. 2018 at 16 EU/US centers were included. A control group treated with chemotherapy (CT) only was also evaluated (NCT02105168). dNLR was collected at baseline (B) and at cycle 2 (C2). Patients were categorized as low vs high dNLR at each timepoint (defined as < vs > 3, as previously done), and the change between B and C2 (good = low at both timepoints, poor = high at both timepoints, mixed = different at each timepoint).

      Result

      1485 patients treated with ICI were analyzed. PDL1 was negative in 162 (11%), 1-49% in 178 (12%), ≥50% in 201 (14%), and missing in 944 (64%). dNLR at B and C2 did not associate with PD-L1 status.

      At baseline, dNLR was high in 509 (34%) patients and associated with worse PFS compared to those patients with low dNLR at baseline (HR 1.56, P<0.0001) and OS (HR 2.02, P<0.0001). At C2, dNLR was high in 484 (34%) and similarly associated with worse outcomes compared to patients with low dNLR at C2 (PFS HR 1.64, P<0.0001; OS HR 2.13, P<0.0001).

      Between B and C2, dNLR remained low in 804 (56%, « good ») or high in 327 (23%, « poor ») or changed in 310 pts (22%, « intermediate »). Those with a good dNLR demonstrated mPFS 5.3, mOS 18.6 mo), followed by those intermediate with mixed dNLR (mPFS 3, mOS 9.2 mo), and finally poor dNLR (mPFS 2, mOS 5mo). Outcomes were independant of PD-L1 expression (adjusted HR for PFS 1.94 for intermediate and 3.16 for poor groups, compared to good dNLR group, P<.001; adjusted HR for OS was 2.08 for intermediate and 3.67 for poor groups, P<0.001).A bootstrap tested the stability of OS/PFS prediction (P<0.001).

      In the chemo-cohort (n=173), high C1-dNLR (n=81, 47%) was not associated with OS (P=0.84).

      Conclusion

      dNLR at baseline, at cycle 2, and the change between these two timepoints associated with outcomes in patients treated with immunotherapy independent of PD-L1, but not in patients treated with chemotherapy alone. dNLR is specifically prognostic in the context of immunotherapy.

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    MA22 - Partnering with Patients to Understand Stigma, Disparities and Values Leading to Improved Lung Cancer Care (ID 154)

    • Event: WCLC 2019
    • Type: Mini Oral Session
    • Track: Advocacy
    • Presentations: 1
    • Now Available
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      MA22.05 - Assessment of Gender Differences in the Psychosocial and Economic Impact on Patients with Stage IV Non-Small Cell Lung Cancer (Now Available) (ID 718)

      15:45 - 17:15  |  Author(s): Margarita Majem

      • Abstract
      • Presentation
      • Slides

      Background

      Incidence of lung cancer in women is rising overtime reporting evident gender-based differences in epidemiology, biology, and treatment outcome. However, little is known about gender-differences regarding psychological, economic and social aspects. The objectives of this prospective study are to evaluate the psychosocial and economic impact of metastatic non-small cell lung cancer (NSCLC), according to gender. Additionally, to assess the emotional burden and the economic impact of the disease on the primary caregiver from a gender perspective

      Method

      Multicenter, prospective, observational, study of two cohorts of patients with metastatic NSCLC (male and female) in Oncology departments of 20 Spanish hospitals. The following measurement tools were used: the APGAR questionnaire (family functionality: adaptability, partnership, growth, affection, and resolve), the Relationship impact scale, the DUKE-UNC scale (perceived socio-affective support), the patient and the caregiver economic impact scale and the Zarit scale (caregiver burden). All questionnaires were performed at the first visit, repeated 4 months later and following the first and second disease progression.

      Result

      Of the 333 pts included, 104 were females and 229 male, of whom 63% and 97%, respectively, were smokers/ex-smokers (p=0.0001). More women than men (85% vs 70%) had adenocarcinomas . The median overall survival was longer in women but did not reach statistical significance [17.1 vs 11.0 months, HR 0.732 (95% CI 0.534 to 1.005), p=0.0524]. Most families considered themselves functional (high score in APGAR questionnaire) with no changes in their partner relationship and social support was evaluated as optimal for majority of patients. Around a quarter of interviewed patients said their economic situation was a little worse after the lung cancer diagnosis, without remarkable differences by gender. Statistically significant differences were found between both groups regarding the caregiver´s relationship to the patient (more parents were the caregiver in females than in males) (p <0.0001) and the caregiver’s employment situation (more employed caregivers in females) (p<0.0001). Most caregivers of both sexes considered that taking care of their relative did not pose a significant burden. No remarkable differences by gender were found between the different variables across the study.

      Conclusion

      This study provides a preliminary insight into gender-related characteristics in the management of advanced NSCLC and its impact on the emotional, social and economic burden of patients and their caregivers, and recall the high priority of researching in cancer from a gender perspective

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    OA13 - Ideal Approach to Lung Resection and Novel Perioperative Therapy (ID 146)

    • Event: WCLC 2019
    • Type: Oral Session
    • Track: Treatment of Early Stage/Localized Disease
    • Presentations: 1
    • Now Available
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      OA13.05 - NADIM Study: Updated Clinical Research and Outcomes (Now Available) (ID 1670)

      11:30 - 13:00  |  Author(s): Margarita Majem

      • Abstract
      • Presentation
      • Slides

      Background

      Patients with stage IIIA (N2 or T4N0) are potentially curable but median overall survival is only around 15 months

      Method

      A Phase II, single-arm, open-label multicenter study of resectable stage IIIA N2-NSCLC in adult patients with CT plus IO as neoadjuvant treatment: 3 cycles of nivolumab (NV) 360 mg IV Q3W + paclitaxel 200 mg/m2 + carboplatin AUC 6 IV Q3W followed by adjuvant NV treatment for 1 year. After completing neoadjuvant therapy, all patients underwent tumor assessment prior to surgery. Surgery was performed during the 3rd or 4th week after day 21 of the 3rd neoadjuvant treatment cycle. The study aimed to recruit 46 patients. The primary endpoint was Progression-Free Survival (PFS) at 24 months. Efficacy was explored using objective pathologic response criteria. Here we present the final data on all study patients that underwent surgical assessment.

      Result

      At the time of submission, the 46 patients had been included. None of the patients were withdrawn from the study preoperatively due to progression or toxicity. 41 patients had undergone surgery and all tumors were deemed resectable with R0 resection in all cases. Intention to treat analysis shows 35 patients (85%; 95% CI, 71; 94%) achieved major pathologic response (MPR) of which 25 (71%; 95% CI, 54; 85%) were complete pathologic responses (CPR). Downstaging was seen in 38 (93%; 95% CI, 80; 98%) of cases. The median follow-up was 13.8 months (P25; P75: 11.7; 16.6 months) for both the whole series and resected patients, and 12 month PFS was 95.7% (95% CI, 84; 99%).

      Conclusion

      This is the first multicentric study to test CT-IO in the neoadjuvant setting in stage IIIA. Neoadjuvant CT-IO with nivolumab in resectable IIIA NSCLC yields a complete pathologic response rate that is higher than ever seen previously, together with a promising PFS which may translate into increased overall survival. EudraCT Number: 2016-003732-20. Clinical trial information: NCT 03081689.

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    P1.04 - Immuno-oncology (ID 164)

    • Event: WCLC 2019
    • Type: Poster Viewing in the Exhibit Hall
    • Track: Immuno-oncology
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
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      P1.04-19 - Association Between Efficacy and irAEs in Patients with Advanced Non-Small Cell Lung Cancer Receiving Immune-Checkpoint Inhibitors (ID 2020)

      09:45 - 18:00  |  Author(s): Margarita Majem

      • Abstract
      • Slides

      Background

      Immune-checkpoint inhibitors (ICIs) are a standard treatment in advanced non-small cell lung cancer (NSCLC). They can induce immune-related adverse events (irAEs) that may compromise treatment continuation.

      We report our experience in advanced NSCLC patients receiving ICIs, the incidence of irAEs and its correlation with efficacy.

      Method

      267 patients with advanced NSCLC receiving ICIs in two Spanish institutions from March 2013 to August 2018 were analyzed. IrAEs were graded following CTCAE v4.0. Kaplan Meier and log-rank tests were used to evaluate progression-free (PFS) and overall survival (OS) using landmark analysis.

      Result

      Median age was 66.1 years [26-85], 70% were male. 86 (32%) patients presented squamous and 181 (68%) non-squamous histology. Most frequent ICIs were nivolumab (44%), pembrolizumab (26%) and atezolizumab (17%), used as monotherapy (78%), in combination with chemotherapy (12%) or with anti-CTLA4 (9%). 30% patients were treated with ICIs in first line and 70% in second line or beyond. Median duration of treatment was 2.8 months [0.1-56.4].

      152 patients (57%) experienced a total of 255 irAEs, and the median number of irAEs/patient was 1 [0-5]. Most frequent irAEs was skin toxicity (34%), followed by diarrhea (16%) and hypothyroidism (11%). 36 patients (14%) presented grade 3-4 irAEs and there were 5 treatment-related deaths: 4 pneumonitis and 1 hepatitis. Patients receiving ICIs in second line or beyond experienced significantly less irAEs (49%) than those treated in first line (74%) (p <0.001).

      With a median follow-up time of 8.5 months [0.3-56.4], the landmark analysis showed that PFS was significantly longer in patients with irAEs: 12.4 months (95%CI, 1.9-22.9) vs 4.1 months (95%CI, 2.6-5.6) (p < 0.001). Similarly, OS among patients with irAEs was significantly higher: 28.2 months (95%CI, not calculated) vs 12.5 months (95%CI, 10.8-14.2) (p < 0.001). Disease control rate was significantly better in patients with irAEs: 77% vs 39%, odds ratio 0.20 (95%CI, 0.11-0.34) (p < 0.001). Besides, duration of response was significantly longer: 6.1 months [0.5-50] vs 2.6 months [0.2-51.9] (p < 0.001).

      44 patients (17%) discontinued treatment due to toxicity. Within this group, 66% patients did not progress after immunotherapy, in contrast to 29% in the rest of the population (p < 0.001).

      Multivariable analysis revealed that cutaneous, endocrinological and reumathological toxicities were significantly associated with increased OS.

      Conclusion

      The presence of irAEs in advanced NSCLC patients treated with ICIs was associated with better outcomes. Patients who discontinued ICIs due to toxicity showed a higher disease control rate.

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    P1.07 - Nursing and Allied Professionals (ID 171)

    • Event: WCLC 2019
    • Type: Poster Viewing in the Exhibit Hall
    • Track: Nursing and Allied Professionals
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
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      P1.07-09 - Implementation of a Nursing Program for Cancer Patients Treated with Immunotherapy by an Immunotherapy Nurse Specialist (ID 1367)

      09:45 - 18:00  |  Author(s): Margarita Majem

      • Abstract
      • Slides

      Background

      Immunotherapy is one of the fastest-evolving areas of oncology to date including non-small cell lung cancer. Due to their mechanism of action they can produce immune related adverse effects (irAES), in which a coordinated multidisciplinary approach is essential for their management, and immunotherapy nurse practice is rapidly changing achieving an important role as a case manager.

      To describe the implementation of a nursing program for cancer patients treated with immunotherapy by an immunotherapy nurse specialist. We present preliminary data that will be updated for the presentation.

      Method

      Before starting immunotherapy, patients receive health education that includes an explanation of the mechanism of action, prohibited medications, possible side effects and the emergency workup that must be followed in case of occurrence. Additionally, all baseline necessary procedures are revised and concomitant medication is registered. An educational booklet specifically made by the nurse is also given, which also includes the contact information of the nursing consult.

      In the follow-up visits, toxicities are identified and graded according to CTCAE v4.0 and the patient's health changes are also summarized. In case of toxicity, the nurse starts the process of referral to the specialist and a close follow-up is carried out. Additionally, virtual follow-up visits and doubts and questions about immunotherapy are also answered.

      Result

      From August 2018 to April 2019 a total of 703 visits and 270 virtual visits have been done by the immunotherapy nurse specialist. 176 cancer patients have been visited and 100 of them had lung cancer. During this period, it has been necessary to refer patients to the specialist on 71 occasions, mostly to endocrinology, rheumatology, dermatology and pulmonology department.

      Conclusion

      The implementation of the immunotherapy nursing program has contributed to an improvement of early detection and management of irAEs in cancer patients receiving immunotherapy as well as a greater patient satisfaction along with a reduction of waiting time for the visit with the specialist.

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    P2.03 - Biology (ID 162)

    • Event: WCLC 2019
    • Type: Poster Viewing in the Exhibit Hall
    • Track: Biology
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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      P2.03-16 - Agreement Between Different Methodologies for Non-Invasive p.T790M and EGFR Sensitizing Mutation Testing (ID 1965)

      10:15 - 18:15  |  Author(s): Margarita Majem

      • Abstract
      • Slides

      Background

      Tyrosine kinase inhibitors (TKIs) are the current standard of care for patients with advanced EGFR-mutant non-small cell lung cancer (NSCLC). However, most patients progressed within 1 to 2 years. The EGFR p.T790M mutation is the most common resistance mechanism to first and second generation EGFR TKIs. The identification of p.T790M mutation is of considerable clinical relevance as osimertinib has demonstrated clinical efficacy in this setting. Guidelines recommend testing for the p.T790M mutation in blood at relapse to TKIs, and re-biopsy only in case of a negative result. Several blood based methodologies for detection of EGFR mutations have been developed in the recent years. However, the number of comparison studies between platforms is very limited.

      Method

      This is a multicenter, cross-sectional study (ClinicalTrials.gov Identifier: NCT03363139) performed by the Spanish Lung Cancer Group. Samples from 75 consecutive EGFR mutant NSCLC patients were collected at disease progression to first line TKI treatment. The presence of EGFR mutations in the cfDNA was evaluated in 39 samples by 7 methodologies, namely: Cobas® EGFR Mutation Test v2 (Roche Diagnostics), Therascreen EGFR Plasma RGQ PCR Kit (Qiagen), QuantStudio® 3D Digital PCR System (Thermofisher), a 5′-nuclease real-time PCR (TaqMan®) assay in presence of PNA, OncoBEAM EGFR (Sysmex Inostics), NGS with two different gene panels: Oncomine® (Thermofisher) and Lung Cancer Panel (Qiagen). The agreement between methodologies was assessed using the kappa coefficient (K) and its corresponding 95% confidence intervals (95% CI). For quantitative variables the concordance correlation coefficient (ccc) was used.

      Result

      Complete results are available for 39 patients. Overall, the agreement between all methodologies for the detection of p.T790M mutation as well as the original EGFR sensitizing mutation was good (K=0.669; 95CI: 0.504-0.835 and K=0.750 95CI: 0.599-0.899 respectively). Remarkably, the agreement between FDA-approved methodologies for p.T790M detection was almost perfect (K=0.926; 95CI: 0.712-1) and good for the EGFR sensitizing mutations (K=0.657; 95CI: 0.417-0.902). Similarly, the agreement between NGS-based methodologies for the detection of p.T790M and the EGFR activating mutations was very high (K=0.843; 95CI: 0.567-1 and K=0.872 95CI: 0.595-1 respectively). Moreover, concordance between both technologies for p.T790M and EGFR sensitizing mutation mutant allele frequency was excellent (ccc=0.956; 95CI: 0.906-1 and ccc=0.980 95CI: 0.950-1 respectively). The proportion of samples that were positive for p.T790M detection varied from 28% (PCR based technologies) to 37% depending on the methodology.

      Conclusion

      NGS and PCR-based methodologies show a good to excellent agreement for the detection of EGFR mutations, including the p.T790M. Our results support the use of liquid biopsies for non-invasive testing of clinically relevant mutations (Data from the whole cohort will be presented at the meeting).

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    P2.04 - Immuno-oncology (ID 167)

    • Event: WCLC 2019
    • Type: Poster Viewing in the Exhibit Hall
    • Track: Immuno-oncology
    • Presentations: 2
    • Moderators:
    • Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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      P2.04-10 - Biomarkers of Pathological Response on Neo-Adjuvant Chemo-Immunotherapy Treatment for Resectable Stage IIIA NSCLC Patients (ID 1466)

      10:15 - 18:15  |  Author(s): Margarita Majem

      • Abstract
      • Slides

      Background

      PD1/PDL1 treatments have become the main therapy in advanced stages of NSCLC due to its significant increase in overall survival (OS), but recently, combination with chemotherapy in locally advanced stages is showing promising results. Many studies have described peripheral blood immune cells parameters as biomarkers of response to immunotherapy. In our study, we described the effect of neo-adjuvant chemo-immunotherapy treatment in Complete Blood Count (CBC) and Peripheral Blood Mononuclear Cells (PBMCs) phenotype, as well as, the association of these parameters with the degree of pathological response.

      Method

      Immune cell populations of 46 resectable stage IIIA NSCLC patients treated with neo-adjuvant chemo-immunotherapy from NADIM clinical trial were analysed. Samples were extracted before initiating the neo-adjuvant treatment with nivolumab plus carboplatin and at the third cycle before patients underwent surgery. We classified patients in 3 subgroups of pathological response assessed in the resection specimen: complete response (pCR), major response (<10% viable tumour) and incomplete response (>10% viable tumour, pIR). Wilcoxon and Mann-Whitney U statistic test were used to evaluate differences between pre and post treatment and between pathological responses groups respectively.

      Result

      From 46 patients, 5 patients did not undergo surgery, so they were excluded from the analysis. Absolute numbers of Leucocytes, Eosinophil, Monocytes, Neutrophils, Haemoglobin and Platelets from hemograms were significantly reduced after neo-adjuvant treatment. However, no changes were observed for Lymphocytes, Basophils, LDH levels or the Lung Immune Prognostic Index (LIPI). Additionally, post-treatment Neutrophil-to-Lymphocyte (NLR), Myeloid-to-Lymphoid lineage (M:L) and Platelets-to-Lymphocytes (PLR) ratios were decreased. Remarkably, from all the CBC absolute numbers and ratios, only PLR variation showed differences between pCR and pIR.

      On the other hand, percentages of PBMCs (T cells, B cells, NK cells and macrophages) did not vary after neo-adjuvant treatment, however activation of CD4 T cells and NK cells as well as PD-1 receptor expression on immune cells were downregulated after neo-adjuvant chemo-immunotherapy. Interestingly, these variations correlate with pCR.

      Conclusion

      In our study, PLR, PD-1 expression, CD4 T cells and NK cells activation are predictive biomarkers of response to treatment. Thus, a higher decrease on PLR post neo-adjuvant treatment is associated to pCR. Moreover, a decrease of PD-1 expression in CD4, CD8 and NK cells, as well as, a reduction of CD4 T cells and NK cells activation after neo-adjuvant treatment, are associated to pCR.

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      P2.04-52 - Impact of Corticosteroids and Antibiotics on Efficacy of Immune-Checkpoint Inhibitors in Patients with Advanced Non-Small Cell Lung Cancer (ID 2015)

      10:15 - 18:15  |  Author(s): Margarita Majem

      • Abstract
      • Slides

      Background

      Immune-checkpoint inhibitors (ICIs) are a standard-of-care in advanced non-small cell lung cancer (NSCLC). Corticosteroids are frequently used in symptomatic advanced NSCLC patients, but their immunosuppressive effect may reduce the efficacy of ICIs.

      Here we report our experience in patients with NSCLC and the potential impact of on-treatment use of corticosteroids and antibiotics.

      Method

      Medical records of 267 patients with advanced NSCLC receiving ICIs from March 2013 to August 2018 were reviewed. Corticosteroid usage at the time of initiation or during ICIs treatment and administration of antibiotics from three months before the initiation of ICIs to 3 months after treatment end were collected. Kaplan Meier and log-rank tests were used to evaluate progression-free (PFS) and overall survival (OS). A multivariable analysis was performed to study the influence of clinical characteristics on treatment efficacy.

      Result

      146 patients (55%) received corticosteroids: 63 (43%) for the treatment of irAEs and 83 (57%) for the management of baseline conditions. Prednisone (40%) and dexamethasone (35%) were the most commonly used types of corticosteroids. Median dose of prednisone equivalent was 50mg daily [5-1250mg], 92% patients received ≥10mg of prednisone equivalent daily. Median duration of corticosteroids was 59 days [0.5-83.0].

      OS was longer in the group of patients that did not receive corticosteroids or received <10mg prednisone equivalent daily: 14.7 months (95%CI, 11.1-18.3) vs 8.3 months (95%CI, 6.9-9.8) (p = 0.009). No differences in PFS were observed: 4.6 months (95%CI, 2.9-6.3) vs 4.2 months (95%CI, 2.5-5.9) (p = 0.359).

      Patients receiving corticosteroids for baseline condition presented shorter median overall survival than the rest of the study population: 6.5 months (95%CI, 4.6-8.3) vs 16.5 months (95%CI, 12.1-20.8) (p <0.001). Multivariable analysis identified corticosteroids usage as an independent variable related to poorer outcomes.

      141 patients (52.8%) received antibiotics. Quinolone (37%) and penicillin (33%) were the most commonly used groups of antibiotics. No correlation between the usage of antibiotics and efficacy of ICIs was found, with median OS of 10.2 months (95%CI, 6.4-13.9) vs 12.5 months (95%CI, 9.9-15.0) (p = 0.924).

      Conclusion

      In our series, corticosteroid use of ≥10mg of prednisone equivalent daily was associated with significantly poorer outcomes, especially when given for baseline condition. No correlation was found between antibiotics and survival. It is important to underline that the use of corticosteroids may simply identify a population with higher volume and aggressive tumors. Prudent use of corticosteroids needs to be warranted.

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    SH01 - Highlight of the Previous Day (ID 98)

    • Event: WCLC 2019
    • Type: Highlight of the Previous Day Session
    • Track:
    • Presentations: 1
    • Now Available
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      SH01.06 - Immunotherapy (Now Available) (ID 3855)

      11:00 - 12:30  |  Presenting Author(s): Margarita Majem

      • Abstract
      • Presentation
      • Slides

      Abstract not provided

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