Bristol-Myers’s Drug Combination Boosts Lung Cancer Benefit

  • Opdivo plus Yervoy shrinks tumors in 39% to 47% of patients
  • Twelve of 13 patients with PD-L1 biomarker responded to drugs

The combination of two Bristol-Myers Squibb Co. drugs that markedly improved the treatment of melanoma appears to have the same benefit for patients with the most common and often deadly form of lung cancer.

Patients getting a mixture of Opdivo and Yervoy had a 39 percent response rate, meaning their tumors shrank after treatment, while the combination using Yervoy less often did better, with 47 percent of patients improving. A separate group getting Opdivo alone had a 23 percent response, though the trial wasn’t designed to directly compare the groups.

The study, dubbed Checkmate 012 and presented at the American Society of Clinical Oncology meeting in Chicago, included 129 patients with newly diagnosed metastatic non-small cell lung cancer, a group that’s typically treated with chemotherapy. Lung cancer is the most deadly tumor type in the U.S., killing more than 158,000 people each year, according to the American Cancer Society.

The combination “is both reassuringly safe and manageable while having very compelling efficacy,” said lead researcher Matthew Hellmann, an oncologist at Memorial Sloan Kettering Cancer Center in New York. The early study “provides encouragement that this combination may truly rival if not exceed the benefits that can be achieved with chemotherapy,” with additional trials under way to test that theory, he said.

O+Y; 12 weeks O+Y; 6 weeksOpdivo alone
ORR/Response47%39%23%
CR/Complete 008%
PR/Partial47%39%15%
PD/Progression13%28%38%
Adverse events82%72%71%
Discontinuation11%13%10%

The combination therapy was most effective in patients with high levels of PD-L1, a protein that helps suppress the immune system. The drugs come from a class known as checkpoint inhibitors, designed to shut down some of the tools that cancer cells use to evade the immune system in their bid for unchecked growth. Twelve of 13 patients with the highest levels of PD-L1, or 92 percent, responded to treatment.

About 70 percent of patients in the study tested positive for PD-L1. They fared better overall, with more than half responding to treatment, Hellmann said. The more their tumors expressed the protein, the more likely they were to shrink after treatment, the study found.

The researchers reduced the dose of Yervoy treatment in the combination arm after earlier work found the more potent mixture caused a “fairly significant” amount of toxicity, Hellmann said. The latest study found the lower-dose combination was safer and similar to Opdivo alone, he said.

The findings represent a compelling improvement in the treatment’s activity, with unprecedented results among those patients with the highest expressions levels of PD-L1, said Nick Botwood, vice president and development lead for lung/head and neck cancers at Bristol-Myers. While the company has a study from the third and final phase needed to win regulatory approval, he declined to say when they may formally file with the U.S. Food and Drug Administration for the combination in lung cancer.

“We’ve really been able to show that we have considerably enhanced the tolerability from the earlier regimens we explored,” he said, and established Opdivo as the foundation drug for treating lung cancer.

NOTE: For more ASCO coverage, see NSE ASCO16

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