CheckMate for nivolumab in untreated melanoma, squamous NSCLC
medwireNews: Two phase III trials published in The New England Journal of Medicine support the use of nivolumab in patients with treatment-naïve metastatic melanoma and in those with squamous non-small-cell lung cancer (NSCLC) who have failed first-line chemotherapy.
Treatment with the anti-programmed death 1 (PD-1) agent resulted in improved outcomes compared with ipilimumab in the metastatic melanoma trial and docetaxel in the squamous cell NSCLC trial.
The trials were reported simultaneously at the 2015 annual meeting of the American Society of Clinical Oncology, held in Chicago, Illinois, USA.
In the double-blind CheckMate067 trial, metastatic melanoma patients randomly assigned to receive nivolumab, either alone (n=316) or together with ipilimumab (n=314), had a significantly longer progression-free survival (PFS) than those given ipilimumab alone (n=315), at a median of 6.9 and 11.5 months versus 2.9 months, respectively.
Participants with malignancies positive for PD-1 ligand (PD-L1) expression had a median PFS of 14.0 months irrespective of whether nivolumab was given alone or in combination with ipilimumab. But in patients with PD-L1–negative tumours, median PFS was shorter in the nivolumab monotherapy group than in the combination treatment arm, at 5.3 and 11.2 months, respectively.
“[T]he use of PD-L1 as a biomarker may allow clinicians to make more informed decisions about the benefit–risk ratio of combination therapy versus monotherapy”, say Jedd Wolchok (Memorial Sloan Kettering Cancer Center, New York, USA) and team.
“However, caution is warranted in interpreting these data because the effects on overall survival are not yet known and because the most effective method and cutoff point for assaying PD-L1 expression remain to be determined.”
The CheckMate017 trial found that in patients with stage IIIB or IV squamous NSCLC, median overall survival (OS) was 9.2 months for the 135 patients randomly assigned to receive open-label, second-line nivolumab. This compared with a median OS of 6.0 months for the 137 patients treated with docetaxel, with a significant hazard ratio for death of 0.59.
Nivolumab treatment also resulted in a significantly higher objective response rate and longer median PFS than docetaxel, at 20% versus 9% and 3.5 versus 2.8 months, respectively.
Interestingly, researcher Julie Brahmer (Sidney Kimmel Comprehensive Cancer Center, Baltimore, Maryland, USA) and colleagues report that tumour PD-L1 expression was “neither prognostic nor predictive” of nivolumab efficacy in this patient population, adding that “PD-L1 testing is not required in order to inform treatment decisions” with nivolumab in this setting.
In both trials, the incidence of adverse events tended to be lowest in the nivolumab group. Treatment-related toxicity of grade 3 or 4 was observed in 16.3%, 55.0% and 27.3% of patients given nivolumab alone, nivolumab plus ipilimumab and ipilimumab alone, respectively, in the CheckMate067 trial.
And in CheckMate017, treatment-related grade 3 or 4 adverse events occurred in 7.0% of nivolumab-treated participants and 55.0% of those given docetaxel.
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