PRINCETON, N.J.—Ah, siblings. They can so often stand so strong together against obstacles and opponents while still having a competitive streak with each other. Perhaps that’s a bit too much personification of inanimate objects—in this case, drugs—but it still sounds good.
To be more specific, Bristol-Myers Squibb is conducting various trials under the name CheckMate, and two of them recently involved the company’s drugs Opdivo (nivolumab) and Yervoy (ipilimumab), producing some promising data. In CheckMate-214, a combination of Opdivo and Yervoy demonstrated superior overall survival and showed durable responses in patients with previously untreated advanced or metastatic renal cell carcinoma (RCC) in the Phase 3 trial vs. sunitinib in intermediate- and poor-risk patients. In Phase 3 CheckMate-238, however, Opdivo and Yervoy went head to head, with the former demonstrating superior recurrence-free survival for patients with resected high-risk melanoma.
So, to start with: CheckMate-214. With a minimum follow-up of 17.5 months in patients with RCC, Opdivo in combination with Yervoy reduced the risk of death 37 percent compared with sunitinib, the current standard of care, in an interim analysis of overall survival (OS) in intermediate- and poor-risk patients, the co-primary endpoint. The median OS had not yet been reached for the combination and was 26 months for sunitinib.
The Opdivo plus Yervoy combination also improved OS in all randomized patients, a secondary endpoint. In this population, the combination reduced the risk of death 32 percent compared with sunitinib. The median OS had not yet been reached for the combination and was 32.9 months for sunitinib.
Results for objective response rate (ORR) and progression-free survival (PFS) in intermediate- and poor-risk patients, the two other co-primary endpoints, were previously reported—those data showed 42 percent for the combo vs. 27 percent for sunitinib in ORR and that PFS improved 18 percent for those receiving the combination, but did not reach the predefined statistical significance threshold of 0.009 compared with sunitinib. The median PFS for the combination group was 11.6 months vs. 8.4 months for the sunitinib group.
“There is an unmet need for additional treatment options in the first-line setting that may provide a meaningful survival benefit including more durable, complete responses for patients with advanced renal cell carcinoma. These results for the combination of nivolumab and ipilimumab are very encouraging in patients with first-line mRCC (metastatic RCC) who have a very poor prognosis,” said Dr. Bernard Escudier, former chair of the genitourinary group of the Institut Gustave Roussy in Villejuif, France.
“As the pioneer in immuno-oncology research, we set a goal of increasing overall survival for more patients by combining agents and have now, for the second time in a Phase 3 trial, demonstrated that the Opdivo plus Yervoy combination may provide a survival advantage for patients,” said Dr. Vicki Goodman, head of new asset development, for Bristol-Myers Squibb. “These positive data showing the Opdivo plus Yervoy combination improved survival in the first-line setting offer the potential—pending regulatory approval—to change the standard of care in the first-line treatment of advanced RCC and may represent a significant step forward for patients with this disease.”
Moving on to the recent CheckMate-238 data, Bristol-Myers Squibb announced that treatment with Opdivo 3 mg/kg resulted in a significant improvement in recurrence-free survival (RFS) compared to Yervoy 10 mg/kg in patients with stage IIIb/c or stage IV melanoma following complete surgical resection.
At this planned interim analysis, Opdivo met its primary endpoint, showing a statistically significant improvement of 35 percent in RFS compared to Yervoy. The 18-month RFS rates for the Opdivo and Yervoy groups, respectively, were 66.4 percent and 52.7 percent. Median RFS had not yet been reached for either group at the time of this analysis. This benefit was consistent across key subgroups, including BRAF mutated and BRAF wildtype patients, and no new safety signals were identified in this trial.
“Despite the rapid development of promising new options for advanced melanoma patients in recent years, those patients with high-risk, resectable melanoma still face a poor prognosis and have an unmet need for more effective adjuvant treatments,” said Dr. Jeffrey S. Weber, deputy director of the Laura and Isaac Perlmutter Cancer Center at NYU Langone Health and professor of medicine at NYU School of Medicine. “The significant RFS results observed with Opdivo in CheckMate-238 are encouraging and provide physicians with new insights into the potential of Opdivo for the management of adjuvant melanoma.”
“These data show Opdivo as the first PD-1 to significantly improve RFS and the only I-O agent to demonstrate superior results, including better tolerance, as compared to an active control, in the treatment of adjuvant melanoma,” remarked Goodman. “These results build upon the significant treatment advance we saw with Yervoy in an adjuvant setting and speak to our leadership and commitment to cancer research through innovative approaches, including exploring much-needed treatment options to address earlier stages of disease.”
