Bristol-Myers Squibb reported top-line results Friday showing that Opdivo (nivolumab) did not significantly prolong overall survival (OS) versus current standard of care in the Phase III CheckMate -331 study of patients with small-cell lung cancer (SCLC) who relapsed following platinum-based chemotherapy. Sabine Maier, development lead for thoracic cancers at Bristol-Myers Squibb, said SCLC "is a highly aggressive disease in which significant unmet need remains," adding that "we are focused on researching innovative oncology therapies to improve outcomes for patients with lung cancer."
The PD-1 inhibitor was given accelerated approval from the FDA in August for use in patients with metastatic SCLC whose disease has progressed after platinum-based chemotherapy and at least one other line of treatment. The approval was based on data from the SCLC cohort of the Phase I/II CheckMate -032 trial, which showed that 12 percent of patients responded to treatment with Opdivo, regardless of PD-L1 expression.
In the CheckMate -331 study, patients who experienced SCLC relapse after platinum-based chemotherapy were randomised to treatment with Opdivo or an active comparator arm consisting of topotecan or amrubicin. The primary endpoint was OS, while secondary goals included progression-free survival and objective response rates. Bristol-Myers Squibb noted that the safety profile in the trial was consistent with previous findings for Opdivo monotherapy in SCLC.
Opdivo was initially cleared in the US in 2014 for the treatment of patients with unresectable or metastatic melanoma. The drug has since been authorised for a number of other indications, including squamous and non-squamous non-small-cell lung cancer. Sales of the therapy reached $1.6 billion in the second quarter.
Commenting on the news, Evercore analyst Umer Raffat indicated that he does not expect the FDA to withdraw Opdivo's accelerated approval in the SCLC patient population, noting that Checkmate -331 is not the only study designed to confirm its benefit. "We saw a similar situation with Roche," he said, referring to the Swiss drugmaker's PD-L1 inhibitor Tecentriq (atezolizumab), which had gained accelerated approval following an advanced bladder cancer study, while the confirming trial failed. "But now, about 1.5 years later, (advanced bladder cancer) remains on the label," Raffat noted.
The analyst also cited several issues with the Checkmate -331 study, including that the trial initially involved 480 patients, whereas in August that rose to about 800. "It's unclear whether we should have read into the trial upsizing," Raffat said. He also pointed out that, unlike other companies testing their treatments in chemotherapy combinations for SCLC, Bristol-Myers Squibb is not evaluating Opdivo in previously untreated patients. "I think [the company] has put itself at a competitive disadvantage by not having a clear (first treatment) trial," Raffat remarked, adding that Checkmate -451, which is assessing Opdivo plus Yervoy (ipilimumab) versus Opdivo alone in SCLC, "is a maintenance trial, whereas Merck & Co., Roche and AstraZeneca are going right into treatment-naive SCLC."
Last month, Roche presented detailed results from the Phase III IMpower133 study demonstrating that patients with previously untreated extensive-stage SCLC who were given Tecentriq plus standard chemotherapy lived significantly longer compared with chemotherapy alone. For related analysis, see ViewPoints: WCLC - Roche sets a new bar in small-cell lung cancer.
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