Astra to challenge Roche in small cell lung cancer

An apparent success in the first-line SCLC Caspian trial could give Imfinzi a new use and allow it to challenge Roche in a setting where Tecentriq secured a US label in March. How well Astra’s drug might compete will not become apparent until the full data are revealed at an upcoming conference, and until a rival first-line study of Merck & Co’s Keytruda, Keynote-604, reads out in December. Keytruda recently scored a third-line US approval, joining Bristol-Myers Squibb’s Opdivo in a setting that could soon be rendered obsolete. Though nothing about the magnitude of Caspian’s overall survival benefit has been revealed, one aspect of the interim result is especially intriguing: Astra says the Imfinzi plus chemo cohort yielded statistical significance versus chemo alone, but does not mention how subjects fared on Imfinzi plus tremelimumab and chemo. This omission suggests that the tremelimumab combo arm might have failed, and if tremelimumab toxicity is accelerating patient deaths this should raise fresh doubts about the relevance of adding CTLA4 inhibition into the mix. Performance of this cohort, and the extent to which survival was driven by PD-L1-positive subjects, should be scrutinised closely.

Selected first-line SCLC trials
Drug Company Study Setting mOS result Trial ID
Opdivo Bristol-Myers Squibb Checkmate-451 + Yervoy + chemo vs chemo Failed (HR=0.92, p=0.3693) NCT02538666
On top of chemo Failed (HR=0.84)
Tecentriq Roche Impower-133 On top of chemo 12.3mth vs 10.3mth (HR=0.70, p=0.007) NCT02763579
Imfinzi Astrazeneca Caspian + tremelimumab + chemo vs chemo Not commented on NCT03043872
On top of chemo Statistically & clinically significant
Keytruda Merck & Co Keynote-604 On top of chemo Due Dec 2019 NCT03066778

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