Immunotherapies Continue to Impress in Lung Cancer Trials

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With advances in screening strategies and targeted therapy for lung cancer, the arrival of immunotherapy looks to be the next big step in helping patients with the disease.

Roy S. Herbst, chief of medical oncology at the Yale Cancer Center and Smilow Cancer Hospital at Yale-New Haven, Connecticut, led some of the first trials of Tarceva (gefitinib), the EGFR inhibitor that helped introduce targeted therapies of this important mutation into the treatment landscape of non-small cell lung cancer (NSCLC). But Herbst believes that many of today’s experimental immunotherapies will soon provide even greater benefit to even more patients. Herbst explained his reasoning during a presentation at the 9th Annual New York Lung Cancer Symposium.

“The trial results for some of these therapies rank among the most exciting things I’ve ever seen,” Herbst said in an interview with OncologyLive. “Several of these treatments are almost certain to win rapid approval and quickly become the standard of care for a large percentage of all patients with lung cancer.”

Herbst’s presentation covered both the theory behind immunotherapy and the performance to date of medications such as nivolumab and Keytruda (pembrolizumab).

Lung cancer specialists are waiting eagerly for results from the phase 3 nivolumab trials, which are expected any time now, but early trial results explain Herbst’s optimism. Results from the CheckMate-063 study, a phase 2, single-arm, open-label study of nivolumab administered as a single agent in patients with advanced NSCLC who have progressed after at least two prior systemic treatments, were announced last month in conjunction with the 2014 Chicago Multidisciplinary Symposium on Thoracic Oncology. After approximately 11 months of minimum follow up, the estimated one-year survival rate was 41 percent and median overall survival was 8.2 months, reported nivolumab’s maker Bristol-Myers Squibb.

Keytruda is also being tested against many tumor types, including NSCLC. Indeed, it is already approved to treat melanoma. Like nivolumab, Keytruda shows activity against both squamous and non-squamous NSCLC. Overall response rates to the compound are just under 20 percent, but they are higher in some subgroups, and those who respond tend to have durable responses.

Progression-free survival in one trial topped 80 weeks for 40 percent of the patients whose tumors appeared likely to respond.

“The durability of the response is one of the most promising aspects of this type of immunotherapy,” Herbst said. “When it works at all, it tends to work for a long time because the immune system, unlike targeted therapies, is designed to attack any foreign cell rather than a single thing that may disappear as tumors mutate.”

Herbst argued during his presentation that official trial results may be understating the benefits of immunotherapies by using the wrong endpoints to evaluate their efficacy. Treatments that work on substantially less than half of all trial patients rarely produce huge improvements in median results, yet those same treatments can greatly increase long-term survival rates, if they provide the durable benefits that immunotherapy seems to offer. Trials may also be understating patient response rates, Herbst said, by failing to detect some instances of “pseudoprogression,” when tumors grow larger even though treatment is working.

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