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A. Atmaca



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    OA 07 - Biomarker for Lung Cancer (ID 659)

    • Event: WCLC 2017
    • Type: Oral
    • Track: Biology/Pathology
    • Presentations: 1
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      OA 07.03a - Impact of Tumor Mutation Burden on the Efficacy of Nivolumab or Nivolumab + Ipilimumab in Small Cell Lung Cancer: An Exploratory Analysis of CheckMate 032 (ID 11063)

      15:45 - 17:30  |  Author(s): A. Atmaca

      • Abstract
      • Presentation
      • Slides

      Background:
      CheckMate 032 is a phase 1/2 clinical trial evaluating nivolumab ± ipilimumab in solid tumors, including small cell lung cancer (SCLC). Initial results have shown durable responses and encouraging survival, with benefit seen regardless of PD-L1 status. There is a need for improved biomarkers in SCLC. SCLC is nearly universally found in smokers and is characterized by high tumor mutation burden (TMB). The association of high TMB and clinical benefit from nivolumab ± ipilimumab in patients with SCLC was evaluated in an exploratory analysis of CheckMate 032.

      Method:
      CheckMate 032 evaluated nivolumab ± ipilimumab in non-randomized and randomized cohorts, which were pooled for this analysis. Whole exome sequencing (WES) was conducted on tumor and matched blood samples. TMB was defined as the total number of nonsynonymous somatic mutations. For the exploratory analyses, patients were equally divided into TMB tertiles (defined as low, medium, and high). Overall survival (OS) and progression-free survival (PFS) were estimated using Kaplan-Meier methods.

      Result:
      Among 401 patients in the intent-to-treat (ITT) population, 211 (53%) had an evaluable TMB result for these analyses (86% of the 246 patients with tissue available to attempt WES). Baseline characteristics and outcomes were similar between the ITT and TMB-evaluable populations. In TMB-evaluable patients treated with nivolumab (n=133), objective response rate (ORR), PFS, and OS were improved in the high TMB cohort vs the medium and low TMB cohorts (ORR: 21.3% vs 6.8% and 4.8%; 1-year PFS: 21.2% vs 3.1% and not calculable; 1-year OS: 35.2% vs 26.0% and 22.1%). Similar benefits were seen in TMB-evaluable patients treated with nivolumab + ipilimumab (n=78) in the high vs medium and low TMB cohorts (ORR: 46.2% vs 16.0% and 22.2%; 1-year PFS: 30.0% vs 8.0% and 6.2%; 1-year OS 62.4% vs 19.6% and 23.4%).

      Conclusion:
      In patients with SCLC, efficacy with nivolumab ± ipilimumab was enhanced in those with high TMB. Among patients with high TMB, ORR and 1-year OS rates were approximately double with nivolumab + ipilimumab compared with nivolumab monotherapy. TMB has a potential role as a biomarker in lung cancer. Optimization of TMB cutoff and prospective investigation are warranted.Acknowledgements: All authors contributed to and approved the abstract; writing and editorial assistance was provided by Beth Burke, PhD, CMPP, of Evidence Scientific Solutions, funded by Bristol-Myers Squibb.Trial Registration: clinicaltrials.gov, NCT01928394

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    P2.07 - Immunology and Immunotherapy (ID 708)

    • Event: WCLC 2017
    • Type: Poster Session with Presenters Present
    • Track: Immunology and Immunotherapy
    • Presentations: 1
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      P2.07-034 - Health Status in Patients with Small-Cell Lung Cancer Treated with Nivolumab Alone or Combined with Ipilimumab: CheckMate 032 (ID 9400)

      09:30 - 16:00  |  Author(s): A. Atmaca

      • Abstract
      • Slides

      Background:
      CheckMate 032 (NCT01928394) is an open-label, phase 1/2 trial evaluating the efficacy and safety of nivolumab monotherapy and nivolumab plus ipilimumab in patients with advanced or metastatic solid tumors. In this study, nivolumab ± ipilimumab showed durable responses, encouraging survival, and manageable safety in patients with small-cell lung cancer (SCLC) that progressed after ≥1 previous platinum-containing regimens. An exploratory objective is to describe changes in patient-reported health status using the EuroQoL-5 Dimensions (EQ-5D) instrument.

      Method:
      The EQ-5D visual analog scale (VAS; scale: 0–100 [worst–best health]; minimally important difference [MID]=7) was assessed in the treatment period at baseline (week 1 prior to study drug administration) and then every 2 weeks in the nivolumab (3 mg/kg) arm and at baseline and then every 3 weeks in the nivolumab (1 mg/kg) plus ipilimumab (3 mg/kg) arm through week 13, and in both arms at subsequent tumor assessments (every 6 weeks until week 24 and every 12 weeks thereafter). After treatment discontinuation, the EQ-5D was assessed at follow-up visits 1 and 2, and at survival visits. EQ-5D VAS mean and mean within-patient change from baseline were estimated at each assessment. Time to first deterioration (TTD) in health status was also evaluated.

      Result:
      In the nivolumab (n=245) and nivolumab plus ipilimumab (n=156) arms, EQ-5D VAS completion rates were 90% and 85%, respectively, at baseline and remained ≥60% at the last assessment (≥5 patients/arm; weeks 97 and 121, respectively). Baseline mean EQ-5D VAS scores for the nivolumab and nivolumab plus ipilimumab arms were 67.1 and 65.2, respectively, scores similar to a lung cancer population norm (68). With monotherapy, EQ-5D VAS mean within-patient changes from baseline suggested health status stability while on treatment (estimated changes
      Conclusion:
      Preliminary EQ-5D VAS results from CheckMate 032 showed that on-treatment health status in patients with recurrent SCLC remained stable with nivolumab and improved (ie, increases in scores exceeded the MID) with nivolumab plus ipilimumab. For patients remaining on treatment for ≥6 months, mean EQ-VAS scores in both arms trended towards the population norm.

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