Opdivo With or Without Yervoy Did Not Prolong Survival in Small Cell Lung Cancer

Opdivo (nivolumab) plus Yervoy (ipilimumab) after first-line chemotherapy did not prolong overall survival, or the length of time from diagnosis or treatment to the point the patient is still alive, in patients with extensive-disease small cell lung cancer, according to data published in the Journal of Clinical Oncology.

Previously, patients with extensive-disease small cell lung cancer would respond to first-line platinum-based chemotherapy, although the response did not last a long time, and patients with recurrent disease have a poor prognosis and limited treatment options. Researchers sought to analyze overall survival with Opdivo plus Yervoy or Opdivo alone following first-line chemotherapy compared to placebo.

After no progression with at least four cycles of first-line chemotherapy, 834 patients were assigned to:

• Opdivo at 1 mg/kg plus Yervoy at 3 mg/kg once every three weeks for 12 weeks, followed by 240 mg of Opdivo once every two weeks (279 patients);
• Opdivo at 240 mg once every two weeks (280 patients);
• or placebo (275 patients).

Patients were treated for up to two years, or until disease progression or unacceptable toxicity. Researchers conducted follow-up for a median of 8.4 months in the Opdivo plus Yervoy group, 9.9 months in the Opdivo alone group and 9.1 months in the placebo group. During follow-up, overall survival was a median of 9.2 months with Opdivo plus Yervoy, 10.4 months with Opdivo and 9.6 months with placebo.

“Compromised (Opdivo) exposure because of increased toxicity with combination therapy might have contributed to the negative study outcome,” the study authors wrote. “Of note, patients in this arm received a median of two (of four planned) treatment cycles, whereas patients on monotherapy (Opdivo) received an eight-fold higher median cumulative nivolumab does (240 mg). This disparity in nivolumab exposure could explain the trend toward greater efficacy with monotherapy.”

Progression-free survival, or the length of time during and after treatment the patient lives with the cancer without disease progression, favored Opdivo alone and Opdivo plus Yervoy compared with placebo. This was also observed with objective response rate. The median progression-free survival was 1.7 months with Opdivo plus Yervoy, 1.9 months with Opdivo alone and 1.4 months with the placebo. Duration of response, or the length of time a tumor continues to respond to treatment without growth or spread, was 10.2 months for the Opdivo plus Yervoy group, 11.2 months for the Opdivo alone group and 8.1 months for the placebo group.

Authors note that there was a survival benefit trend seen in patients younger than 65 years with Opdivo plus Yervoy and Opdivo alone. There was also an overall survival benefit seen with Opdivo plus Yervoy in patients with tumor mutational burden, mutations found in the DNA of cancer cells, of at least 13 mutations per megabase.

There were no new safety signals found in the treatments, but severe side effects occurred in 85.6% of patients assigned Opdivo plus Yervoy, 60.9% in those assigned Opdivo alone and 50.2% in patients assigned placebo. In addition, life-threatening side effects were observed in 52.2% of patients who received Opdivo plus Yervoy, 11.5% who received only Opdivo and 8.4% who received placebo. The most common side effects associated with Opdivo plus Yervoy related to skin (47.5%), the gastrointestinal system (27.3%) and liver failure (18.3%). The most common side effects seen with Opdivo alone were related to skin (22.6%), gastrointestinal system (14.7%) and endocrine system (12.5%).

Overall, there were nine treatment related deaths: seven with Opdivo plus Yervoy, one with Opdivo and one with the placebo.

“In conclusion, maintenance with combination therapy in the current dosing regimen did not prolong (overall survival) in patients with (extensive-disease small cell lung cancer) after first-line platinum-based chemotherapy,” the study authors wrote. “Investigation into alternative dosing regimens for either experimental arm explored in this study or alternative combination therapies for maintenance treatment that reflect the unique histology and natural history of (small cell lung cancer) offer improved tolerability may be warranted.”

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