Keytruda gets okay from FDA for adjuvant melanoma

The US FDA has approved Merck & Co’s Keytruda as an adjuvant treatment for patients with melanoma who have had surgery but still show some evidence of cancer in their lymph nodes.

It’s the first time that PD-1 inhibitor Keytruda (pembrolizumab) has been approved in the US for adjuvant use in any cancer, although Merck picked up European approval for this indication in December.

Keytruda’s approval in this indication comes on the back of the phase III KEYNOTE-054 trial, which showed that giving the drug after surgery for high-risk, stage III melanoma significantly prolonged recurrence-free survival (RFS), cutting the risk of disease recurrence or death by 43% compared to placebo.

After 15 months of follow-up, 12-month rates of RFS were 75% for pembrolizumab and 61% for placebo, widening to 71% versus 53% at the 19-month timepoint.

The green light is yet another example of Merck muscling into territory already claimed by its arch-rival Bristol-Myers Squibb as the two fight for dominance in the rapidly expanding checkpoint inhibitor market.

BMS’ PD-1 inhibitor Opdivo (nivolumab) was approved for adjuvant melanoma therapy in the US at the end of 2017 and in Europe last year, giving it a short lead over Keytruda in this clinical setting. Now, Merck can try to encroach on that territory on both sides of the Atlantic as it consolidates an already-dominant position for Keytruda in the big lung cancer market.

First-to-market Opdivo outsold Keytruda from when the two drugs were approved in 2014 until last year, when Keytruda overtook its rival with sales of $7.17bn and $6.74bn, respectively.

BMS’ older cancer immunotherapy Yervoy (ipilimumab), a CTLA4 inhibitor, is also FDA-approved as a single agent for adjuvant melanoma, getting a green light from the FDA in 2015, but fell out of favour after Opdivo was shown to be more effective and easier to tolerate.

The company says Keytruda is the first anti-PD1 therapy to be evaluated in the adjuvant setting across patients with stage IIIA, stage IIIB, and stage IIIC melanoma, and is now approved for four skin cancer indications.

“Not too long ago, there were limited treatment options for patients with advanced melanoma,” said Marc Hurlbert, chief science officer of the Melanoma Research Alliance.

“Today’s approval of KEYTRUDA in the adjuvant setting provides melanoma patients with another option to prevent their cancer from returning, giving hope to those facing this disease.”

Until the emergence of cancer immunotherapies, the only adjuvant options for melanoma patients were interferons and – for patients with BRAF-positive tumours – kinase inhibitors such as Novartis’ Tafinlar (dabrafenib) and Mekinist (trametinib).

Both Keytruda and Opdivo are also being developed for neoadjuvant therapy, in other words when drugs are given prior to surgery in order to reduce the tumour mass and improve the chances of long-term remission.