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David M Waterhouse



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

    • Event: WCLC 2019
    • Type: Oral Session
    • Track: Immuno-oncology
    • Presentations: 1
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      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): David M Waterhouse

      • 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.

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    P1.14 - Targeted Therapy (ID 182)

    • Event: WCLC 2019
    • Type: Poster Viewing in the Exhibit Hall
    • Track: Targeted Therapy
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
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      P1.14-18 - ALK Inhibitor Sequencing and Outcomes Among ALK-Positive (ALK+) NSCLC Patients in the US Community Oncology Setting (ID 731)

      09:45 - 18:00  |  Author(s): David M Waterhouse

      • Abstract
      • Slides

      Background

      Several ALK inhibitors, including 2nd and 3rd generation agents are available for patients with ALK+ NSCLC. Treatment patterns and outcomes with use of multiple sequential ALK inhibitors is limited.

      Method

      A retrospective observational cohort study of patients with ALK+ NSCLC treated with 1st generation (crizotinib) and 2nd generation (alectinib, brigatinib, ceritinib) ALK inhibitors from 1 September 2011 to 31 December 2017. Structured data were obtained via programmatic extraction from the iKnowMed EHR database of the US Oncology Network. Patient demographics and treatment sequences were characterized. Index was the start date of the first ALK. Duration of therapy (DOT) from index to end of the last ALK, and overall survival (OS) were assessed using the Kaplan-Meier method.

      Result

      A total of 410 ALK+ NSCLC patients were included. Median age at index was 62 years, 54% were female, 78% Caucasian, 87% adenocarcinoma histology, and 54% never smokers. 233 (57%), 144 (35%), and 33 (8%) patients received 1, 2, or 3-4 different ALK inhibitors, respectively. Crizotinib monotherapy (50%) was most common. Among patients that received 2 or more ALK inhibitors (n=177), most were crizotinib-led sequences. In 59% of patients, chemotherapy was given prior to the first ALK (median time from start of chemo to index 6.64 mo), and 53% of patients ended their ALK sequence and received subsequent chemo. Median cumulative ALK DOT in the full study population, regardless of line of therapy or sequence was 16 mo (95% CI 6-19). Median OS from index for the full study population was 28 mo (95% CI 24, 36). Median OS among patients who received 1, 2, or 3-4 ALK inhibitors was 15 mo (95% CI 10, 22), 42 mo (95% CI 38, 60) and 56 mo (95% CI 31, 72).

      Conclusion

      Patients received a range of 1 to 4 ALK inhibitors. Crizotinib-led sequences were most common, likely reflecting the approval history of ALK inhibitors during the study period. Longer DOT and OS were observed in patients receiving multiple ALK inhibitors. This study provides an initial view of treatment patterns following the emergence of new ALK inhibitors and suggests feasibility of sequential ALK therapies. Follow-up studies will help improve understanding of outcomes of patients treated with 2nd generation-led sequences.

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    P2.06 - Mesothelioma (ID 170)

    • Event: WCLC 2019
    • Type: Poster Viewing in the Exhibit Hall
    • Track: Mesothelioma
    • Presentations: 1
    • Now Available
    • Moderators:
    • Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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      P2.06-04 - Treatment Patterns and Outcomes of Advanced Malignant Pleural Mesothelioma (MPM) Patients in a Community Practice Setting (Now Available) (ID 723)

      10:15 - 18:15  |  Author(s): David M Waterhouse

      • Abstract
      • Slides

      Background

      MPM is an aggressive neoplasm with a poor prognosis and limited therapeutic options. Pemetrexed+platinum is standard of care (SOC) for advanced MPM in the United States with cisplatin doublet as the only approved first-line (1L) treatment by the Food and Drug Administration (FDA). There are no FDA approved treatments in second-line (2L) or later. Understanding how patients are currently treated and the associated outcomes is important to assess the unmet needs in MPM.

      Method

      Retrospective data were abstracted from the US Oncology Network’s iKnowMed electronic health record (EHR) for patients with advanced MPM receiving systemic therapy between 01-Jan-2008 and 31-Dec-2016, followed through 31-Dec-2017. Eligibility criteria: ≥18 years of age, ≥2 visits, no clinical trial enrollment or other malignancy during study period. Baseline demographic/clinical characteristics, treatment patterns, duration of chemotherapy (DOT) and overall survival (OS) were assessed, using Kaplan-Meier methods for 1L, 2L+ survival.

      Result

      474 advanced MPM patients receiving treatment were identified; median age was 72 years, majority were male (82%) with an Eastern Cooperative Oncology Group (ECOG) score of 0 to 1 (71%). Cisplatin+pemetrexed (n=194; 41%) and carboplatin+pemetrexed (n=175; 37%) were the most frequent 1L regimens, followed by pemetrexed monotherapy (n=51; 11%). Only 108 (23%) patients received 2L and 33 (7%) received 3L. The most common 2L regimens included monotherapies gemcitabine (n=40; 37%), pemetrexed (n=27; 25%), vinorelbine (n=9; 8%), and IO therapy (avelumab, nivolumab or pembrolizumab n=9; 8%). Median DOT was 2.7 months in 1L SOC and 1.7 months in all 2L regimens. Unadjusted median OS in patients 1L SOC was 14.0 months (95%CI, 11.6-17.0) with similar survival observed among cisplatin+pemetrexed (13.7 months; 95%CI, 10.8-18.5) and carboplatin+pemetrexed (14.2 months; 95%CI, 11.1-19.8); OS for 1L pemetrexed monotherapy (10.7 months; 95%CI,6.2-14.3). Unadjusted OS in 2L was 6.4 months (95%CI, 5.1-7.6) ranging from 3.4 months (95%CI, 2.7-6.5) with gemcitabine to 11.8 months (95%CI, 0.3-NR) with immunotherapies.

      Conclusion

      This real-world analysis of advanced MPM showed a majority of 1L patients received SOC pemetrexed+platinum based therapy, with carboplatin almost as common as cisplatin. The platinum agent paired with pemetrexed in 1L SOC did not affect unadjusted survival in the community setting. Less than a quarter of 1L patients received a 2L therapy, with gemcitabine as the most common treatment. Overall survival in MPM remains poor and treatment rates in 2L are low, highlighting the need for more effective therapies.

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