Merck’s strong Phase II data testing Keytruda with chemotherapy in first-line lung cancer may put pressure on future IO/IO combinations when it comes to toxicity, efficacy and – importantly – cost.
Merck & Co. Inc. presented the first positive Phase II data comparing the PD-1 inhibitor Keytruda (pembrolizumab) in combination with chemotherapy versus chemotherapy alone at the European Society for Medical Oncology (ESMO) meeting Oct. 9 and the data could raise the bar for future immuno-oncology combinations.
While the data are early, the positive results seen in the KEYNOTE-021 study suggest the combination of Keytruda with chemotherapy could become a new standard for treating first-line non-small cell lung cancer patients who test negative for PD-L1. The regimen also could be an option for some PD-L1 positive NSCLC patients.
The lower cost of an IO/chemo combination will raise the bar for IO/IO combinations.
The chemo combo data could have implications long-term in a critical area of drug development. If PD-1/L1 inhibitors prove to be an effective treatment in combination with chemotherapy, the regimen could put more pressure on the IO/IO combinations in which manufacturers are investing heavily. Both IO/IO and IO/chemo combos carry significant toxicities, but the cost of an IO/IO combo would most likely be much higher.
As Bernstein research analyst Tim Anderson pointed out in a same-day research note on the Keytruda/chemo data, “Yes, the combination brings with it all the toxicity of standard chemotherapy – but that is what patients are getting today anyway. Compared to alternative combinations involving branded IO drugs, the cost would be less, putting pressure on those manufactures of IO/IO combinations to fully substantiate their value to cost-minded payers,” he said.
Merck will ultimately need to confirm the positive results seen in KEYNOTE-021 with overall survival data in Phase III studies. Two Phase III trials testing different chemotherapy combinations are ongoing with results expected in the second half of 2017. One of the studies, KEYNOTE-189, follows a similar design as KEYNOTE-021, while the other is testing Keytruda in combination with carboplatin and paclitaxel or nab-paclitaxel in patients with squamous NSCLC.
The KEYNOTE-021 results were overshadowed at ESMO by the surprising news that Bristol-Myers Squibb Co.’s rival – and market-leading – PD-1 inhibitor Opdivo (nivolumab) almost inexplicably failed to show a benefit in first-line NSCLC patients even among those stratified to a high PD-L1 threshold, while Merck has released positive overall survival data for Keytruda in the patient population, changing the dynamics of a market that many investors expected to unfold in Bristol’s favor.
Bristol previously released disappointing Phase III data in first-line lung cancer in patients with lower levels of PD-L1 expression. (Also see "Does CheckMate 026 Take Bristol Out Of The End Game?" - Scrip, 5 Aug, 2016.) But many of the company’s investors were holding out hope the results would be different in patients with a high PD-L1 status, as the data with Keytruda have shown in first-line lung cancer. (Also see "Merck Poised To Be First To Market With A PD-1 For First-Line Lung Cancer" - Scrip, 16 Jun, 2016.) However, Bristol revealed at ESMO that Opdivo didn’t even show a benefit in NSCLC patients with a high PD-L1 status. Meanwhile, Merck presented the full positive data in first-line lung cancer from KEYNOTE-024 at the meeting.