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Patient Selection Vital in Ensuring Improved Response to PD-1, PD-L1 Inhibitors in NSCLC

Surabhi Dangi-Garimella, PhD
A late afternoon extended education session on the first day of the 2017 American Society of Clinical Oncology Annual Meeting in Chicago, Illinois, was a discussion on the state-of-the-art uses for immunotherapy in the management of non-small cell lung cancer (NSCLC).
Melissa Lynne Johnson, MD, associate director of lung cancer research at Sarah Cannon Research Institute, addressed the conundrum of choosing a suitable immunotherapy agent.

She explained that PD-1 and PD-L1 inhibitors are monoclonal antibodies. The interesting thing is that different PD-1 inhibitors bind different faces of the PD-L1 protein. “They also block different protein-protein interactions,” which might result in differences in patient responses based on which drug is administered.

Variability also arises from IGG isotypes and antibody-dependent cell-mediated cytotoxicity (ADCC). “Avelumab is the only immunotherapy drug that has retained its ADCC function, compared with nivolumab, durvalumab, pembrolizumab, and atezolizumab,” Johnson said.

Another source of variability in response arises from the PD-L1 assay used to assess protein expression.

Patient adverse events (AEs) associated with the treatment have varied, Johnson said. The rate of AEs has hovered around 76% for nivolumab, Johnson said, much higher than pembrolizumab (67.5%), atezolizumab (65%), durvalumab (60.6%), and avelumab (67%).

The survival data in the second-line setting has found that median OS is 12.2 months for nivolumab, compared with docetaxel for non-squamous NSCLC; 10.4 months with pembrolizumab, compared with 8.5 months with docetaxel; and 13.8months for atezolizumab, compared with 9.6 months.

In the first-line setting, however, nivolumab has lagged behind pembrolizumab, Johnson showed. The median progression-free survival for nivolumab is 4.2 months for nivolumab, compared with 5.9 months for chemotherapy. Pembrolizumab, on the other hand, has a median PFS of 10.3 months. While median OS for nivolumab is 14.4 months, it has not yet been reached for pembrolizumab.

Johnson drove home the point that cost vs convenience is another question that both physicians and patients are concerned with. Nivolumab is administered every 2 weeks (both 240 mg and 3 mg/kg doses) and costs about $21,990 for a 6-week treatment. Pembrolizumab is administered once in 3 weeks (both 240 mg and 2 mg/kg doses) and costs about $21,662 over 6 weeks.

She proposed the idea of evaluating these agents over a long treatment interval, to both lower costs and lower the inconvenience of frequent administration for patients.

Johnson summarized her presentation by saying that in the first-line setting, understanding the role of the tumor microenvironment might help understand the differences in patient response, as will identifying additional biomarkers. “Until then, dosing schedule and cost will continue to play a significant part in oncologists’ decision making,” she said.

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