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Salvage immunotherapy viable for non-small cell lung cancer
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NEW YORK — Immunotherapy remains a viable option for pretreated patients with non-small cell lung cancer, but the data are rapidly evolving, according to a presenter at HemOnc Today New York.
“We have come a long way with the development of checkpoint inhibitors, and we have to remember that they became famous and exerted their effect in the chemotherapy-refractory setting first,” Benjamin Levy, MD, assistant professor of oncology at Johns Hopkins University and clinical director of Sidney Kimmel Cancer Center at Sibley Memorial Hospital in Washington, said during his presentation.
Several studies have shown monotherapy with agents such as pembrolizumab (Keytruda, Merck), nivolumab (Opdivo, Bristol-Myers Squibb) and atezolizumab (Tecentriq, Genentech) outperform second-line docetaxel in mostly unrestricted patient populations.
“This was a blitzkrieg of information we received, really within the past 3 years,” Levy said. “These drugs have now firmly been cemented into the therapeutic armamentarium for non-small cell lung cancer in the second line.”
The absence of randomized head-to-head data makes it difficult to know which agent is most effective in this setting. However, cross-trial comparisons show the outcomes look pretty similar across most trials, Levy said.
The CA209-003 study assessed nivolumab in patients with advanced solid tumors, including 129 patients with NSCLC. All patients had ECOG performance status of 0 or 1, and they had received up to five lines of prior systemic therapy (median, three).
Data presented at least year’s American Association for Cancer Research Annual Meeting showed 5-year OS of 16%.
“If you put this in the context of what we generally think the 5-year OS is, this is significantly raising the bar,” Levy said. “More importantly, what we have to start to understand and grapple with is, who are these patients who are living long term? We need to try to understand what is going on with these patients that is allowing them to garner such a benefit from these drugs.”
Results of the combined Checkmate-017 and Checkmate-057 showed patients with advanced NSCLC who received second-line therapy with single-agent nivolumab achieved significantly loner 3-year OS than those who received docetaxel (17% vs. 9%).
“We haven’t seen those numbers ever in advanced non-small cell lung cancer,” Levy said. “Understanding molecularly, from a microbiome standpoint, and from a clinical standpoint why these patients derive such a benefit is really important.”
The question of how long salvage treatment with immunotherapy should be continued had not been established.
The CheckMate-153 trial included 220 patients with NSCLC who received 1 year of nivolumab treatment. Researchers randomly assigned patients to continue treatment or stop it.
Results presented at last year’s European Society for Medical Oncology Congress showed improved PFS among patients who continued the drug until progression (median, not reached vs. 23.2 months; HR = 0.63; 95% CI, 0.33-1.2). Researchers also observed a trend toward 1-year OS (88% vs. 81%).
“We always grapple with patients who are long-term survivors and [the question of] when should we stop,” Levy said. “These data tell us we should keep going until patients either are not tolerating the therapy or the tumor is progressing.” – by Mark Leiser
Reference:
Levy B. Salvage immunotherapy in NSCLC. Presented at: HemOnc Today New York; March 8-10, 2018; New York.
Disclosure: Levy reports consultant/advisory board roles with AstraZeneca, Celgene, Eli Lilly, Genentech, Merck and Takeda, as well as research funding from Boehringer Ingelheim and Celgene.