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Silvia Novello



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    FP13 - Immunotherapy (Phase II/III Trials) (ID 247)

    • Event: WCLC 2020
    • Type: Posters (Featured)
    • Track: Immunotherapy (Phase II/III Trials)
    • Presentations: 1
    • Moderators:
    • Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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      FP13.01 - 5-Year Survival Update From KEYNOTE-010: Pembrolizumab Versus Docetaxel in Previously Treated, PD-L1–Positive Advanced NSCLC (ID 1371)

      00:00 - 00:00  |  Author(s): Silvia Novello

      • Abstract
      • Presentation

      Introduction

      The KEYNOTE-010 study (NCT01905657) showed significantly improved OS with pembrolizumab 2 or 10 mg/kg Q3W versus docetaxel in patients with previously treated advanced NSCLC with PD-L1 TPS ≥50% and ≥1%. We provide long-term follow-up for KEYNOTE-010 including updated efficacy outcomes in patients who completed 35 cycles (2 years) of pembrolizumab and those who received second-course pembrolizumab.

      Methods

      Patients had previously treated advanced NSCLC with PD-L1 TPS ≥1% and were randomized 1:1:1 to receive pembrolizumab 2 or 10 mg/kg Q3W or docetaxel 75 mg/m2 Q3W. Pembrolizumab treatment continued for 35 cycles (~2 years) or until disease progression/unacceptable toxicity. Eligible patients who completed pembrolizumab treatment or stopped pembrolizumab after achieving CR and receiving ≥6 months of treatment could receive second-course of pembrolizumab for up to 17 cycles (1 year) following disease progression after stopping pembrolizumab. Response was assessed Q9W. Survival was assessed every 2 months after treatment ended. Primary endpoints were OS and PFS in patients with PD-L1 TPS ≥50% and in those with PD-L1 TPS ≥1% (total population). Pembrolizumab in the pembrolizumab dose groups were pooled for this analysis.

      Results

      1033 patients were included in these analyses (pembrolizumab, 690; docetaxel, 343). As of April 8, 2020, median (range) time from randomization to data cutoff was 67.4 (60.0‒77.9) months. OS and PFS favored pembrolizumab in patients with PD-L1 TPS ≥50% and ≥1% (Table). Seventy-nine patients in the pembrolizumab group completed 35 cycles or 2 years of treatment with ORR of 98.7% (15 CR, 63 PR) in this group. Among those who completed 35 cycles or 2 years of pembrolizumab, 61 patients (77.2%) were alive (38 of whom were alive without PD). The 3-year OS rate after completing 35 cycles or 2 years (ie, at approximately 5 years) was 83.0%. Twenty-one patients received second-course pembrolizumab; 15 (71.4%) were alive at data cutoff. ORR after starting second-course was 52.4% (1 CR, 10 PR) and 6 had SD. Eight patients with CR/PR/SD after starting second-course subsequently had PD.

      Table.

      Patients with PD-L1 TPS ≥50%

      Patients With PD-L1 TPS ≥1%

      Pembrolizumab

      (N = 290)

      Docetaxel

      (N = 152)

      Pembrolizumab

      (N = 690)

      Docetaxel

      (N = 343)

      Median OS,a mo (95% CI)

      16.9 (12.3‒21.4)

      8.2 (6.4‒9.8)

      11.8 (10.4‒13.1)

      8.4 (7.6‒9.5)

      HR (95% CI)

      0.55 (0.44‒0.69)

      0.70 (0.61‒0.80)

      5-year OS rate,a %

      25.0

      8.2

      15.6

      6.5

      Median PFS,a,b mo (95% CI)

      5.3 (4.2‒6.5)

      4.2 (3.8‒5.1)

      4.0 (3.1‒4.1)

      4.1 (3.8‒4.5)

      HR (95% CI)

      0.57 (0.46‒0.71)

      0.84 (0.73‒0.96)

      5-year PFS rate,a %

      18.2

      Not reached

      9.4

      0.7

      aKaplan-Meier estimate.

      bAssessed by independent central review per RECIST version 1.1.

      Conclusion

      With more than 5 years of follow-up, pembrolizumab continued to provide clinically meaningful improvement in OS and PFS versus docetaxel in patients with previously treated, PD-L1–positive advanced NSCLC; 5-year OS rates were more than doubled in pembrolizumab-treated patients. Patients who completed 35 cycles or 2 years of pembrolizumab had durable clinical benefit. Second-course pembrolizumab provided meaningful disease control in the majority of patients who had disease progression after 2 years of pembrolizumab treatment.

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    FP14 - Targeted Therapy - Clinically Focused (ID 252)

    • Event: WCLC 2020
    • Type: Posters (Featured)
    • Track: Targeted Therapy - Clinically Focused
    • Presentations: 1
    • Moderators:
    • Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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      FP14.05 - LIBRETTO-431: Selpercatinib in Treatment-Naïve Patients with RET Fusion-Positive Non-Small Cell Lung Cancer (NSCLC). (ID 807)

      00:00 - 00:00  |  Author(s): Silvia Novello

      • Abstract
      • Slides

      Introduction

      Selpercatinib (LOXO-292) is a highly selective and potent inhibitor of RET signaling. In the LIBRETTO-001 Phase I/II trial, selpercatinib treatment resulted in a 64% objective response rate (ORR) (95% confidence interval [CI]: 54-73%) in the registration dataset (n=105) of patients with RET+ NSCLC who previously received platinum-based chemotherapy and an 85% ORR (95% CI: 70-94%) in treatment-naïve patients with RET+ NSCLC (n=39). Although the duration of response (DOR) and progression free-survival (PFS) were not yet mature in treatment-naïve patients, in patients who previously received chemotherapy, the median DOR was 18 months (95% CI: 12-not estimable [NE]), median PFS was 17.5 months (95% CI: 12-NE), and CNS ORR per RECIST 1.1 was 91% (95% CI: 59-100%) (n=10/11). The most common adverse reactions included dry mouth (39%), diarrhea (37%), hypertension (35%), and fatigue (35%). The majority of adverse reactions were Grade 1 or Grade 2. The most common lab abnormality was increased alanine aminotransferase (ALT) (51%)/aspartate transaminase (AST) (45%). A total of 5% of patients discontinued due to an adverse reaction.

      The LIBRETTO-431 trial, is a global, open-label, randomized, controlled, Phase 3 trial evaluating selpercatinib vs platinum-based and pemetrexed treatment +/- pembrolizumab in treatment-naïve patients with locally advanced or metastatic RET+ non-squamous NSCLC (NCT04194944).

      Methods

      Patients will be randomized to receive selpercatinib 160 mg BID in 3-week cycles (Arm A) or pemetrexed (500 mg/m2 IV) in 3-week cycles plus investigator’s choice of carboplatin (AUC 5) or cisplatin (75 mg/m2 IV) for 4 cycles (Arm B). For patients in Arm B, at the investigator’s discretion, pembrolizumab (200 mg IV) may also be given for up to 35 cycles and patients may receive maintenance pemetrexed +/- pembrolizumab. Crossover to selpercatinib is allowed for Arm B patients who have disease progression. Treatment will be discontinued for progressive disease, unacceptable toxicity, decision to withdraw or death. Stratification factors include geography: East Asian versus non-East Asian, brain metastases: presence versus absence, and intended treatment if randomized to Arm B: +/- pembrolizumab. RET status may be determined in tumor (by PCR or NGS) or in blood (by NGS) using a qualified local test or a Lilly-enabled regional test. Key eligibility criteria include age ≥18 years; treatment-naïve; non-squamous Stage IIIB-IIIC not suitable for surgery/radiation therapy or Stage IV NSCLC; measurable disease by RECIST 1.1; ECOG performance status 0-2. Key exclusion criteria include presence of other known oncogenic drivers and symptomatic central nervous system metastases. Tumor assessments will be performed until progressive disease, the start of a new anticancer treatment, death or study completion. The co-primary endpoint, PFS by independent review in intent-to-treat (ITT) patients with pembrolizumab (if assigned to control), will act as a gatekeeper to the co-primary endpoint PFS by independent review in the ITT population. Secondary endpoints include investigator assessed PFS, ORR/DOR, intracranial ORR/DOR, overall survival, time to deterioration in pulmonary symptoms, progression after the next line of therapy, RET fusion status: local versus central, and safety/tolerability. The study was initiated in March 2020 and enrollment is ongoing.

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    PL03 - Bench to Bedside (Immunology) (Japanese, Mandarin, Spanish Translation Available) (ID 142)

    • Event: WCLC 2020
    • Type: Plenary
    • Track: N.A.
    • Presentations: 1
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      PL03.01 - Chair (ID 3909)

      18:00 - 20:00  |  Presenting Author(s): Silvia Novello

      • Abstract

      Abstract not provided

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    PS01 - Presidential Symposium (Japanese, Mandarin, Spanish Translation Available) (ID 143)

    • Event: WCLC 2020
    • Type: Plenary
    • Track: N.A.
    • Presentations: 1
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      PS01.04 - International Tailored Chemotherapy Adjuvant Trial : ITACA Trial. Final Results (ID 1820)

      07:00 - 09:00  |  Presenting Author(s): Silvia Novello

      • Abstract
      • Presentation
      • Slides

      Introduction

      Adjuvant platinum-based chemotherapy in early stage non-small cell lung cancer confers a modest 5% overall survival benefit. Different strategies have been investigated to improve these results. mRNA expression of some genes was correlated with the sensitivity or resistance to specific anticancer agents. We aimed to evaluate the predictive utility of the mRNA expression levels of molecular markers ERCC1 and TS.

      Methods

      An open label, randomized, comparative phase III investigator-initiated study (EudraCT 2008-001764-36) of adult patients (aged > 18 years), with an ECOG performance status of 0 or 1 and with a completely resected stage II-III NSCLC according to the 6th edition of the TNM staging System was planned. We enrolled patients from 17 Italian centers and 13 German Centers within 6-12 weeks after radical surgery.

      Genomic analyses were performed soon after surgery and then patients were randomly assigned in each of the 4 genomic subgroups to investigator’s choice of platinum-based chemotherapy (C1-2-3-4) or chemotherapy defined by the molecular markers. In the tailored arm patients with tumors that had high ERCC1 and high TS received single-agent docetaxel (T1); patients with high ERCC1 and low TS received single-agent pemetrexed (T2); patients with low ERCC1 and high TS received cisplatin and gemcitabine (T3); finally, patients with low ERCC1 and low TS received cisplatin and pemetrexed (T4). All anticancer drugs were administered according to standard doses and schedules. We randomly allocated patients with 1:1 ratio centrally using permuted blocks sizes and stratified by stage and smoking status. The primary end point of the study was overall survival according to an intent to treat analysis. For the final statistical analysis all the control arms were grouped in one (control arm) and all tailored chemotherapies in another one (experimental arm).

      Results

      Between December 2008 and August 2014, 773 patients were enrolled and randomly assigned to the treatment groups: 389 to arms C and 384 to arms T (T1, n=148, T2, n=43, T3, N=101, T4, N=92).

      Six hundred and ninety patients were included in the intent to treat analysis. In the control arm the following regimens were used: cisplatin /gemcitabine (n=159, 50.0%), cisplatin /viborelbine (n=123, 38.7%), cisplatin/docetaxel (n=23, 7.2%), platinum/pemetrexed (n=5, 1.6%), others (n=8, 2.5%). At a median follow up of 28.2 months (IQR: 9.9-55.8 months), 86 (24.9%) and 68 (19.8%) patients were deceased in arms C and T, respectively. The estimated median overall survival in arm C was 83.5 months (95%CI: 60.1-not defined) and in arm T was 96.4 months (95%CI: 81.8-not defined; hazard ratio (group T vs. group C) was 0.76 (95%CI: 0.55-1.04; p=0.091). Grade 3-5 toxicities that were reported more frequently in arm C (control) than in arm T (tailored) were neutropenia (18.9% vs 13.4%), leukopenia (13.3% vs 3.9%), thrombocytopenia (7.7% vs 3.3%) and anaemia (2.7% vs 0.9%).

      Conclusion

      In completely resected stage II-III NSCLC tailoring adjuvant chemotherapy on the basis of the mRNA expression of selected genes do not confer a statistically significant survival advantage in terms of overall survival and relapse-free survival and toxicity was less commonly reported in the customization arms.

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    PS02 - Presidential Symposium (Re-Broadcast) (Japanese, Mandarin, Spanish Translation Available) (ID 275)

    • Event: WCLC 2020
    • Type: Plenary
    • Track: N.A.
    • Presentations: 1
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      PS02.04 - International Tailored Chemotherapy Adjuvant Trial : ITACA Trial. Final Results (ID 4285)

      18:00 - 20:00  |  Presenting Author(s): Silvia Novello

      • Abstract
      • Slides

      Introduction
      Adjuvant platinum-based chemotherapy in early stage non-small cell lung cancer confers a modest 5% overall survival benefit. Different strategies have been investigated to improve these results. mRNA expression of some genes was correlated with the sensitivity or resistance to specific anticancer agents. We aimed to evaluate the predictive utility of the mRNA expression levels of molecular markers ERCC1 and TS. Methods

      An open label, randomized, comparative phase III investigator-initiated study (EudraCT 2008-001764-36) of adult patients (aged > 18 years), with an ECOG performance status of 0 or 1 and with a completely resected stage II-III NSCLC according to the 6th edition of the TNM staging System was planned. We enrolled patients from 17 Italian centers and 13 German Centers within 6-12 weeks after radical surgery.

      Genomic analyses were performed soon after surgery and then patients were randomly assigned in each of the 4 genomic subgroups to investigator’s choice of platinum-based chemotherapy (C1-2-3-4) or chemotherapy defined by the molecular markers. In the tailored arm patients with tumors that had high ERCC1 and high TS received single-agent docetaxel (T1); patients with high ERCC1 and low TS received single-agent pemetrexed (T2); patients with low ERCC1 and high TS received cisplatin and gemcitabine (T3); finally, patients with low ERCC1 and low TS received cisplatin and pemetrexed (T4). All anticancer drugs were administered according to standard doses and schedules. We randomly allocated patients with 1:1 ratio centrally using permuted blocks sizes and stratified by stage and smoking status. The primary end point of the study was overall survival according to an intent to treat analysis. For the final statistical analysis all the control arms were grouped in one (control arm) and all tailored chemotherapies in another one (experimental arm).

      Results

      Between December 2008 and August 2014, 773 patients were enrolled and randomly assigned to the treatment groups: 389 to arms C and 384 to arms T (T1, n=148, T2, n=43, T3, N=101, T4, N=92).

      Six hundred and ninety patients were included in the intent to treat analysis. In the control arm the following regimens were used: cisplatin /gemcitabine (n=159, 50.0%), cisplatin /viborelbine (n=123, 38.7%), cisplatin/docetaxel (n=23, 7.2%), platinum/pemetrexed (n=5, 1.6%), others (n=8, 2.5%). At a median follow up of 28.2 months (IQR: 9.9-55.8 months), 86 (24.9%) and 68 (19.8%) patients were deceased in arms C and T, respectively. The estimated median overall survival in arm C was 83.5 months (95%CI: 60.1-not defined) and in arm T was 96.4 months (95%CI: 81.8-not defined; hazard ratio (group T vs. group C) was 0.76 (95%CI: 0.55-1.04; p=0.091). Grade 3-5 toxicities that were reported more frequently in arm C (control) than in arm T (tailored) were neutropenia (18.9% vs 13.4%), leukopenia (13.3% vs 3.9%), thrombocytopenia (7.7% vs 3.3%) and anaemia (2.7% vs 0.9%).

      Conclusion
      In completely resected stage II-III NSCLC tailoring adjuvant chemotherapy on the basis of the mRNA expression of selected genes do not confer a statistically significant survival advantage in terms of overall survival and relapse-free survival and toxicity was less commonly reported in the customization arms.

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