The PD-1 immune checkpoint inhibitor nivolumab improves survival compared with docetaxel for subsequent treatment of advanced nonsquamous non-small cell lung cancer (NSCLC), as shown in results of the phase 3 CheckMate 057 study presented in at the 2015 Americal Society of Clinical Oncology (ASCO) annual meeting in Chicago, IL.1

Options for treatment of patients with nonsquamous NSCLC who progress after initial therapy are limited—principally docetaxel is used if that agent was not part of prior therapy.2

Outcomes with subsequent therapies after platinum-based CT in general provide only minimal improvements in overall survival. In a previous phase 3 trial, nivolumab demonstrated improved survival compared with docetaxel for the treatment of previously treated squamous NSCLC.

This led to its approval in March 2015 as subsequent therapy of squamous NSCLC and its incorporation into the most recent National Comprehensive Cancer Network guidelines as a treatment option in this setting.2

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Patients in the CheckMate 057 study had progressed after treatment with platinum-based doublet chemotherapy (CT) (and, if eligible, a tyrosine kinase inhibitor), a guideline-recommended first-line therapy for nonsquamous NSCLC. They were randomly assigned to subsequent treatment with nivolumab (3 mg/kg every 2 weeks; 292 patients) or docetaxel (75 mg/m2 every 3 weeks; 290 patients); both drugs were continued until progression or discontinuation due to toxicity.

The primary efficacy endpoint of the study was overall survival (OS). Treatment with nivolumab significantly improved median OS, with a hazard ratio for death of 0.73 (95% CI: 0.59, 0.89; P=0.00155) compared with docetaxel. One-year OS was 50.5% with nivolumab versus 39.0% with docetaxel.1

Other study endpoints included progression-free survival (PFS), objective response rate (ORR), and nivolumab efficacy by PD-L1 expression.

Significantly more patients had an objective response (19.2% vs. 12.4%; P=0.0235). At the time of the analysis, the median duration of response to nivolumab was 17.1 months, compared with 5.6 months for docetaxel.

No difference between nivolumab and docetaxel was observed in median PFS (2.3 months vs. 4.2 months; P=0.393). PD-L1 expression was associated with improved efficacy for patients treated with nivolumab, an effect most dramatically seen in patients with PD-L1 expression 5% or higher and 10% or higher, but evident at PD-L1 expression levels as low as 1% or higher.

Also of note, subgroup analysis favored nivolumab over docetaxel in all categories, except patients 75 years of age or older, never smokers, and those positive for EGFR mutations.

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Treatment-related adverse reactions of grade 3 to 5 severity occurred at a higher rate with docetaxel (53.7%) than with nivolumab (10.5%).1

Luis Paz-Ares, MD, PhD, from the Hospital Universitario Virgen Del Rocio, Spain, presented the results at ASCO.

He noted that “CheckMate 057 is the second phase 3 trial to demonstrate superior survival with nivolumab over docetaxel” in advanced NSCLC. Roy S. Herbst, MD, PhD, from the Yale Comprehensive Cancer Center in New Haven, CT, commented that this study showed “a particularly long benefit” in these patients and that nivolumab is less toxic than docetaxel.

Although PD-L1 expression was associated with improved survival and ORR, he noted that even patients without PD-L1 expression did at least as well as those treated with docetaxel.

Dr. Herbst added that the survival benefit across multiple patient subgroups combined with lower toxicity recommends nivolumab as a new standard of care for patients with previously treated nonsquamous NSCLC.

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