CheckMate 012: Nivolumab plus chemo less than stellar




CHICAGO– Combining the PD-1 checkpoint inhibitor nivolumab with first-line chemotherapy for advanced non–small cell lung cancer produced responses no better than those previously reported for chemotherapy alone, according to results of CheckMate 012.

There was a “hint” of benefit with one of the regimens, however, prompting study author Dr. Scott J. Antonia to argue that the combination treatment strategy should not be abandoned.

Dr. Scott J. Antonia Patrice Wendling/Frontline Medical News

Dr. Scott J. Antonia

Nivolumab 5 mg plus paclitaxel/carboplatin resulted in an “encouraging” 18-month overall survival rate of 86%, a lack of progressors at first evaluation, and a median overall survival that had yet to be reached at 2 years.

Overall, responses were independent of programmed death-1 (PD-1) status and toxicity was manageable.

“It is my opinion that these data support further development of concurrent bimodality therapies,” Dr. Antonia from the Moffitt Cancer Center, Tampa, said at the Chicago Multidisciplinary Symposium in Thoracic Oncology, where the data were presented.

Session comoderator Dr. Karen Kelly from University of California–Davis Comprehensive Cancer Center, Sacramento, said in an interview, “At best, there was a hint” of benefit with the combination. The results also have to be put into perspective of the “very, very small” sample size and weighed against the increase in side effects.

In all, 23 of the 56 patients had a grade 3 adverse event and 2 had a grade 4 event. There were no treatment-related deaths, but 12 patients discontinued therapy because of treatment-related adverse events.

Still, Dr. Kelly agreed that combination PD-1 inhibition and chemotherapy should continue to be explored.

“Absolutely,” she said, but added, “I suspect we’ll see the exact same finding with all of the other trials. It’s been very consistent across the refractory stage diseases, every drug has been the same.”

Nivolumab is under review for non–small cell lung cancer (NSCLC) in Europe, and drug developer Bristol-Myers Squibb is expected to complete submission for third-line, pretreated squamous cell NSCLC in the United States by year’s end.

Nivolumab is already under priority review in the United States for pretreated advanced melanoma, and it became the world’s first approved PD-1 inhibitor with the July 2014 approval for unresectable melanoma in Japan, where it is sold under the trade name Opdivo.

PD-1 inhibitors have proven to be very active drugs in NSCLC, raising the inevitable question of whether they would be even more effective when combined with chemotherapy.

CheckMate 012 assigned 56 patients with chemotherapy-naive stage IIIb or IV NSCLC to platinum-based doublet chemotherapy given in four 21-day cycles plus nivolumab 10 mg/kg or 5 mg/kg intravenous every 3 weeks until disease progression or unacceptable toxicity.

Patients with squamous histology got nivolumab 10 mg plus gemcitabine (Gemzar) 1,250 mg/m2 and cisplatin (Platinol) 75 mg/m2; nonsquamous patients got nivolumab 10 mg plus pemetrexed (Alimta) 500 mg/m2 and cisplatin 75 mg/m2; and patients with any histology got either nivolumab 10 mg or 5 mg plus paclitaxel (Taxol) 200 mg/m2 and carboplatin AUC 6.

The patients’ median age was 64 years, 96% had stage IV disease, and 66% had adenocarcinoma. Five percent of patients had prior erlotinib (Tarceva), but none were in the nivolumab 5-mg group.

The objective response rate for nivolumab 10 mg/kg was 33% with gemcitabine/cisplatin, 47% with pemetrexed/cisplatin, and 47% with paclitaxel/carboplatin, Dr. Antonia said. Stable disease was reported in 58%, 47%, and 27%.

The objective response rate for the 14 patients in the nivolumab 5 mg/kg arm fell in the same range at 43%. Stable disease was also 43%.

Despite being given the higher 10-mg dose of nivolumab, overall survival at 18 months was only 33% for those also on gemcitabine/cisplatin, 60% for pemetrexed/cisplatin, and 40% for paclitaxel/carboplatin. Median overall survival was 51 weeks, 83 weeks, and 65 weeks, he said.

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