Opdivo-Yervoy Combo Delays Need for Additional Treatment in Renal Cell Carcinoma Patients, Phase 3 Data Shows

Opdivo-Yervoy Combo Delays Need for Additional Treatment in Renal Cell Carcinoma Patients, Phase 3 Data Shows

A combination of Opdivo (nivoumab) and Yervoy (ipilimumab) significantly delayed the need for a subsequent treatment in patients with advanced or metastatic renal cell carcinoma who had not previously been treated, compared with the standard of care Sutent (sunitinib), a Phase 3 trial called Checkmate-214 shows.

The benefits were seen across several patient groups, including those who discontinued treatment.

These trial findings were revealed recently during the European Society for Medical Oncology 2018 Congress in Munich.

David F. McDermott, MD, director of the immuno-oncology program at Beth Israel Deaconess Medical Center and one of the trial investigators, presented the poster, “Treatment-free interval (TFI) following discontinuation of first-line nivolumab plus ipilimumab (N+I) or sunitinib (S) in patients (Pts) with advanced renal cell carcinoma (aRCC): CheckMate 214 analysis.”

“The results from this analysis of CheckMate -214 provide important insights into the potential for sustained clinical benefit with the combination of nivolumab and ipilimumab in patients with advanced renal cell carcinoma, for whom there is a considerable unmet need,” McDermott said in a press release.

The Phase 3 CheckMate-214 trial (NCT02231749) tested the combination of Opdivo and Yervoy as a treatment for newly diagnosed renal cell carcinoma patients with advanced or metastatic disease.

It included 1,096 patients who were randomly assigned the combo treatment or Pfizer’s Sutent, a medicine approved by the U.S. Food and Drug Administration for the treatment of renal cell carcinoma.

In 2017, results had shown that the combination significantly improved several outcomes over Sutent, including response rates, time to disease progression or death, and overall survival.

These findings led Bristol-Myers Squibb to request the combination’s approval for this indication in Europe, but the European Medicines Agency’s advisory committee did not recommend its approval, citing a lack of evidence on how exactly Yervoy contributed to the benefits.

Researchers are now reporting additional benefits of the combination, which significantly extended the time patients lived without the need for a subsequent treatment from 8.5 months to 15.4 months.

After a median follow-up of 30 months, 36% of patients receiving the combination were alive and had not needed an additional treatment, compared with only 16% of those assigned to Sutent.

Interestingly, the benefits were seen even in patients who had discontinued treatment. At the time of the analysis, 75% of patients receiving Opdivo plus Yervoy had stopped treatment, either due to disease progression or to treatment-related adverse events. In the Sutent arm, 85% had also stopped treatment.

But while 19% of patients who had taken the combination did not require a second treatment for 18 months or more after discontinuing, only 4% of those receiving Sutent did.

The differences were particularly evident among patients who had responded — partially or completely — before discontinuing treatment, with 42% of patients on the combination group living two years or more after discontinuation without needing another therapy, versus 12% of those on Sutent.

But patients who had achieved stable disease also benefited more from the combination, with 12% of them reaching the 18-month mark without a second treatment, versus 6% of those on Sutent.

Opdivo plus Yervoy also delayed subsequent treatment regardless of PD-L1 levels — a marker of response to PD-1/PD-L1 inhibitors like Opdivo. Among those with PD-L1 expression in their tumors, 27% who received the combination remained alive and treatment-free for two years or more, versus 8% on Sutent.

For those with very little to no PD-L1 production, the combination kept 18% of patients alive and treatment-free for two or more years, while Sutent did so in only 5% of patients.

“This latest analysis demonstrating sustained clinical benefit over time builds on the existing body of evidence from CheckMate -214 regarding superior overall survival and durable response, regardless of PD-L1 expression, and reinforces our ongoing commitment to improving outcomes for adults living with the most common type of kidney cancer,” said Arvin Yang, MD, PhD, development lead, melanoma and genitourinary cancers, Bristol-Myers Squibb.

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