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Two Immunotherapy Drug Combination Offers Chemotherapy-Free Option for Advanced NSCLC

(ESMO 2019) Sept 28, 2019 - New data have shown that first-line treatment with a combination of two immunotherapy drugs improves overall survival in a subset of patients with advanced non-small cell lung cancer (NSCLC) compared to chemotherapy (1). The data from the CheckMate-227 trial, reported at the ESMO Congress 2019, suggest that the combination of nivolumab plus low-dose ipilimumab could offer a chemotherapy-free option for first-line treatment of patients with advanced NSCLC. Nivolumab, a PD-1 antibody, and ipilimumab, an anti-cytotoxic T-lymphocyte antigen 4 (CTLA-4) antibody, are immune checkpoint inhibitors with distinct but complementary mechanisms of action.

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H. Jack West, MD (Posted: October 01, 2019)

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The impact of the CheckMate-227 trial remains to be seen. While it was positive for an overall survival benefit, this was observed in the patients with PD-L1 expression 50%, but not in the patients with PD-L1 expression in between. This pattern doesn't give us a lot of confidence. At the same time, the OS benefit was compared to chemo alone, while the current standard of care is now chemo/pembro in most of these patients (certainly those with PD-L1 <1%), in whom there was a significant survival benefit seen in the KEYNOTE-189 and KEYNOTE-407 trials for patients with advanced non-squamous and squamous NSCLC, respectively. I expect that the appeal of a non-chemotherapy regimen will have some appeal to patients and oncologists, but we should recognize that non-chemo doesn't mean non-toxic. I expect that nivo/ipi will be a minor player compared to our current standards, likely used in <10% of patients in front line advanced NSCLC.

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