New Immunotherapy May Extend Lives Of Some Lung Cancer Patients

MedicalResearch.com Interview with:
Dickran Kazandjian, MD
Office of Hematology and Oncology Products
Center for Drug Evaluation and Research
US Food and Drug Administration
Silver Spring, Maryland

Medical Research: What is the background for this study? What are the main findings?

Dr. Kazandjian: Nivolumab is the first approved immunotherapy, for the treatment of metastatic squamous non–small-cell lung cancer (NSCLC) after platinum-based chemotherapy.  FDA initiated an expedited review after obtaining the data monitoring committee report of a planned interim analysis of a second-line squamous NSCLC trial demonstrating a large overall survival benefit (CheckMate 017).

Nivolumab efficacy in metastatic Squamous (SQ) NSCLC has been previously reported in two studies.  CheckMate 063 was a single-arm trial in 117 patients with metastatic SQ NSCLC who had progressed after previous treatment with 2 systemic regimens including platinum-based doublet chemotherapy (Rizvi et al)  CheckMate 017 was a randomized study of nivolumab compared to docetaxel in 272 patients with metastatic SQ NSCLC who had progressed after prior platinum-based doublet chemotherapy (Brahmer et al).  The median survival of patients randomized to nivolumab was 9.2 months vs 6.0 months for docetaxel (hazard ratio, 0.59; 95%CI, 0.44-0.79; P < .001) a 41% improvement in the risk of death. Approval was supported by the single-arm study which demonstrated an objective response rate of 15% and at the time of analysis, 10 of the 17 responding patients (59%) had response  durations of 6 months or longer. The FDA approved nivolumab on March 4, 2015, saving 6 months by not waiting for formal preparation of data by the sponsor and 2.5 months by expediting review.

Medical Research: What should clinicians and patients take away from your report?

Dr. Kazandjian: Metastatic SQ NSCLC is a serious and life-threatening malignant condition. In late December 2014, the FDA obtained the data monitoring committee report of a planned interim analysis of Study CheckMate 017 that demonstrated an overall survival benefit for patients treated with nivolumab compared with docetaxel.  This trial demonstrated an improvement in overall survival.  However, more studies are needed to identify predictive biomarkers and understand the utility of PD-L1 testing to predict clinical benefit in SQ NSCLC. Additional data are also needed to assess the scope and long-term outcomes of the immune-related adverse events and their management.

Medical Research: What recommendations do you have for future research as a result of this study?

Dr. Kazandjian: Nivolumab is the first head-to-head trial against an active control (docetaxel) in second line squamous NSCLC to demonstrate a large survival benefit. Survival is the gold standard for clinical benefit because it is objective and not influenced by potential bias.  It is unclear if ORR or PFS fully capture the clinical benefit of immunotherapy; further research is needed to explore novel end points for activity estimation and assessment of clinical benefit.  Future trials will need to use nivolumab in the control arm as a new standard of care or otherwise soundly justify not using it.

Citation:

Kazandjian D, Khozin S, Blumenthal G, et al. Benefit-Risk Summary of Nivolumab for Patients With Metastatic Squamous Cell Lung Cancer After Platinum-Based Chemotherapy: A Report From the US Food and Drug Administration. JAMA Oncol.Published online October 15, 2015. doi:10.1001/jamaoncol.2015.3934.

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Dickran Kazandjian, MD (2015). New Immunotherapy May Extend Lives Of Some Lung Cancer Patients 

Last Updated on October 24, 2015 by Marie Benz MD FAAD