Stage 3 melanoma was the first cancer area to have an FDA-approved immunotherapy to prevent disease from returning after surgery. Now, Merck & Co.’s Keytruda has shown it can do the same in stage 2 skin cancer.
Compared with placebo, Keytruda cut the risk of disease returning or death by 35% when used in patients following complete resection of high-risk stage 2 melanoma, Merck said at the European Society of Medical Oncology 2021 virtual congress.
With the showing, the FDA plans a priority review for Merck’s application for Keytruda as an adjuvant treatment for patients 12 and older with stage 2b or 2c melanoma. The agency has set a target action date of Dec. 4.
Merck’s Keytruda, Bristol Myers Squibb’s rival PD-1 inhibitor Opdivo and CTLA-4 drug Yervoy are all allowed as adjuvant therapy after surgery to reduce the risk of stage 3 melanoma recurrence. Unlike stage 3 melanoma, stage 2 disease hasn’t spread to the lymph node, Scot Ebbinghaus, M.D., vice president of clinical research at Merck Research Laboratories, explained in an interview.
The current phase 3 KEYNOTE-716 trial enrolled stage 2b/2c patients, who have poorer prognostic factors in the stage 2 group. This high-risk patient population is roughly the same size as those with stage 3 disease, Ebbinghaus said. Current treatment guidelines recommend simple observation for stage 2 melanoma.
After 14.4 months of median follow-up, the median time to disease recurrence or death wasn’t reached in either arm. But 82 patients (16.8%) in the control arm saw their disease return, while only 54 patients (11.1%) on Keytruda experienced that outcome. Twenty-three Keytruda takers and 38 patients in the placebo had distant or metastatic recurrences.
Besides adjuvant treatment for stage 3 melanoma, Keytruda is also approved for newly diagnosed metastatic melanoma.
Meanwhile, there's also the question of whether patients can receive Keytruda again in the metastatic setting after disease recurrence from adjuvant treatment.
In the second part of the ongoing KEYNOTE-716 trial, Keytruda patients who recurred can get the immunotherapy again as long as the relapse didn’t happen within six months of completing the first stage of treatment. Placebo patients can also access the immunotherapy upon disease progression.
This trial design allows Merck to collect data on how patients fare when receiving Keytruda for the recurrent disease, Ebbinghaus said.
The KEYNOTE-716 trial will continue follow patients longer to see whether early Keytruda treatment can prolong patients’ lives.
PD-1/L1 agents are increasingly looking at perioperative cancer settings for their next phase of growth. For Keytruda, the PD-1 king recently won a go-ahead for use both before and after surgery in early triple-negative breast cancer after an FDA about-face. It also showed that its postsurgery use could slash the risk of disease returning or death over placebo in clear cell renal cell carcinoma.