Bristol-Myers Squibb delivered a major shock last week by confirming that its PD-1 inhibitor Opdivo failed to demonstrate progression-free survival (PFS) or overall survival (OS) benefit in first-line non-small-cell lung cancer patients. An aggressive trial design for the Checkmate-026 study – in particular a low 'cut-off' point when defining PD-L1 expression – appears to be the culprit for this failure.
The implications could be far-reaching, but in the short term will primarily impact Merck & Co.'s competing PD-1 inhibitor Keytruda. Utilising a study design with a higher PD-L1 expression cut off (>50 percent PD-L1+ versus the >5 percent PD-L1+ used in Checkmate-026), Merck's Keynote-024 study demonstrated both a PFS and OS benefit in favour of Keytruda versus chemotherapy in first-line NSCLC patients, the company announced earlier this year.
The upshot is potential early dominance of the first-line opportunity by Keytruda; a segment of the market that analysts had expected Opdivo to dominate given its strong penetration of the second-line setting. In addition, analysts have been quick to speculate that Keytruda may benefit from a 'halo' effect in second- and third-line patients, while it remains to be seen how oncologists construe failure of Opdivo in the Checkmate-026 study.
To better understand the immediate implications stemming from Opdivo's failure in Checkmate-026, FirstWord's latest Physician Views poll is asking US and EU5-based oncologists the following questions…
Assuming Keytruda gains approval for the treatment of first-line NSCLC patients with >50 percent PD-L1+, how quickly do you expect adoption to occur in this population?
Following approval would you anticipate any off-label use of Keytruda in lower-expressing first-line patients or will Opdivo's failure to achieve PFS/OS endpoints in a broader population limit this?
Very significant use
Given the respective top-line results for Keytruda and Opdivo in first-line patients, do you expect this to have a positive impact on the use of Keytruda in second- and third-line patients? (note: Keytruda is pending approval for second-line NSCLC in EU)
Very significant impact
Has your perception of Opdivo (i.e. as a second-line treatment for NSCLC per its label) changed materially following its failure to demonstrate PFS or OS benefit in first-line NSCLC patients with >5 percent PD-L1+?
No – perception the same
Yes – marginally
Yes – moderately
Yes – significantly
Yes – very significantly
Will the failure of Opdivo to demonstrate a PFS/OS benefit in a broader first-line patient population make you more likely to test second-line patients for PD-L1 status prior to treatment with a PD-1 inhibitor (Opdivo or Keytruda)?
Results and related analysis will be published for FirstWord Pharma PLUS subscribers to read, with the opportunity for non-FirstWord Pharma PLUS subscribers to purchase these findings. To be notified when poll results and analysis become available, please click here.
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