Dive Brief:

• Merck won an expected, but crucial U.S. approval on Wednesday of its combination of Keytruda (pembrolizumab) and chemotherapy for first-line treatment of non-small cell lung cancer, broadening the drugmaker's edge over its immunotherapy rivals in the lucrative market. 
• Importantly, the Food and Drug Administration approved the combination for use in NSCLC patients regardless of PD-L1 expression. Keytruda had previously been approved as a monotherapy in the first-line setting, but only for those patients whose tumors express high levels of PD-L1, a protein marker used to identify responders. 
• Keytruda now is the only checkpoint inhibitor approved in first-line NSCLC as both a monotherapy and combination, a competitive advantage that should help the drugmaker cement market share and stay a step ahead of Roche, Bristol-Myers Squibb and AstraZeneca. 

Dive Insight:

While sales of Bristol-Myers competing immunotherapy Opdivo (nivolumab) continue to outpace those of Keytruda, Merck's edge in first-line lung cancer is expected to quickly narrow that gap.

Roughly 40% of Keytruda's $584 million in first-quarter sales were in NSCLC, driven by faster uptake and increased testing for PD-L1 expression. Annual sales of Keytruda in 2017 are forecast to reach about $3.6 billion, according to consensus estimates, reflecting an acceleration as first-line use gathers steam. 

The FDA approved Keytruda for use only in combination with Eli Lilly's Alimta (pemetrexed) and carboplatin, a commonly used chemotherapy regimen. Merck believes initial adoption of the combo will be only in cases where physicians would prescribe Alimta, but expects that will broaden to use with other chemotherapies over time (although Merck would not be allowed to promote that off-label). 

Approval was supported by data from a 123-patient cohort of Merck's Keynote-021 study, which compared use of the combination to treatment with just Alimta and carboplatin. Keytruda in combination with the other two drugs demonstrated a 55% objective response rate, compared to 29% in those treated with the chemo regimen alone. 

Median progression-free survival for the Keytruda/chemo combo was 13 months, versus 8.9 months for Alimta/carboplatin. At this point, there is no overall survival data comparing the two groups.

More data from this study will come at the annual meeting of the American Society for Clinical Oncology in June, and a Phase 3 trial (Keynote-189) is set to read out in the fourth quarter of this year. The FDA approved the combo on an accelerated basis, meaning the positive results will need to be confirmed by the Keynote-189 study. 

While accelerated approvals have become somewhat routine in the immunotherapy space, Roche just disclosed a confirmatory trial of its immunotherapy Tecentriq (atezolizumab) in advanced bladder cancer failed, potentially jeopardizing an earlier approval.  

Even though Merck may have first-mover advantage in first-line NSCLC, its rivals are close on its heels. 

AstraZeneca, Roche and Bristol-Myers are all planning to read out data over the next three to nine months from trials testing combination therapies pairing their respective checkpoint inhibitors with other drugs. Strong data — particularly any demonstration of an overall survival benefit — from those studies could shift the lung cancer market yet again.