BMS hails Opdivo and Yervoy combo in melanoma

Source: PMLive.com, April 2015

New PD-1 therapy shines against the world’s first immunotherapy for skin cance.

Combining Bristol-Myers Squibb’s PD-1 inhibitor Opdivo and older melanoma drug Yervoy boosted progression-free survival (PFS) compared to Yervoy alone in a clinical trial.

The data – reported at the American Association of Cancer Research (AACR) meeting in Philadelphia – showed that the combination achieved an objective response rate (ORR) of 61% compared to 11% for Yervoy alone when given to previously-untreated patients with advanced (stage III or IV) melanoma

That looks encouraging given trials of Opdivo (nivolumab) as a monotherapy in this patient group revealed an ORR of around 40%, although different trial designs clearly mean no direct comparison can be made.

Giving Opdivo alongside anti–CTLA-4 antibody Yervoy (ipilimumab) resulted in a complete response in 22% of patients, while PFS was increased by 60% and – at the time of reporting – had still not reached a median after 11 months of follow-up.

Michael Giordano, head of oncology development at BMS, said the “results reinforce our belief that the future lies in the combination of immuno-oncology agents".

CTLA-4 and PD-1 exert their effects through complementary mechanisms and in preclinical models inhibiting both seems to have a synergistic improvement on anti-tumour activity.

The results have also been published in the New England Journal of Medicine (NEJM), with the authors concluding that the combination “resulted in durable responses and a substantially higher objective response rate, longer progression-free survival, and higher rates of complete response than ipilimumab monotherapy."

Yervoy quickly established itself as one of the cornerstones of melanoma therapy after launch and achieved sales of $1.3bn last year, and the new add to the body of evidence suggesting Opdivo should be used earlier in therapy than at present.

At the moment Opdivo – along with rival drug Keytruda (pembrolizumab) from Merck & Co – are approved as second-line agents for melanoma after treatment with Yervoy or a BRAF inhibitor such as Roche’s Zelboraf (vemurafenib) and GlaxoSmithKline’s Tafinlar (dabrafenib) if the patient’s tumour is BRAF V600 mutation positive.

Like Opdivo, Keytruda has also shown superiority to Yervoy in a head-to-head clinical comparison also reported in the NEJM this week.

Moreover, both drugs were endorsed as first-line treatments by the National Comprehensive Cancer Network in the US – which means that insurers will likely reimburse them in this setting even ahead of formal approval of first-line use, and there is already evidence of off-label use in combination with Yervoy.

ISI Evercore analyst Mark Schoenenbaum said in a research note that the combination of Opdivo and Yervoy is likely to become the standard of care for first-line melanoma therapy. Further insights into the benefits of combining the two drugs will come with the results of the phase II CheckMate-067 study, which is due to complete in September 2016.