It was billed as one of the highlights of the World Lung conference and the 13-month overall survival benefit Imfinzi delivered in its pivotal Caspian trial in small cell lung cancer did not disappoint, leaving the product on track for a US filing.
However, sometimes good is not quite good enough. The positive results from Caspian do not look as if they will allow Imfinzi to seriously challenge Roche’s Tecentriq, or replace it as the go-to first line SCLC treatment. This leaves Merck & Co’s Keytruda as the only real threat to Tecentriq in the first-line setting, though for confirmation of this observers will have to wait until December when the Keynote-604 study is due to read out.
The 13 month overall survival generated by Imfinzi, combined with chemotherapy, is pretty much comparable to the 12.3 months on which Roche’s Tecentriq was approved in March.
The Astra drug was also similar to Tecentriq on other measures, including an overall survival hazard ratio of 0.73 versus Tecentriq’s 0.70 and progression-free survival of 5.1 months against Tecentriq’s 5.2. As it stands, then, Imfinzi is likely to be judged another useful product in the oncologist's arsenal, rather than a game-changer.
|Selected first-line SCLC trials|
|Drug||Company||Study||Setting||mOS result||Trial ID|
|Tecentriq||Roche||Impower-133||On top of chemo||12.3mth vs 10.3mth (HR=0.70, p=0.007)||NCT02763579|
|Imfinzi||Astrazeneca||Caspian||On top of chemo||13.0mth vs 10.3mth (HR=0.73, p=0.005)||NCT03043872|
|+ tremelimumab + chemo vs chemo||Yet to report|
|Keytruda||Merck & Co||Keynote-604||On top of chemo||Due Dec 2019||NCT03066778|
There is one area where Imfinizi might have an advantage over Tecentriq. Unlike the Roche drug, Imfinzi was tested with both carboplatin and cisplatin chemotherapy regimens. This is important as the chemotherapy standard of care varies across countries, with European physicians preferring cisplatin and US doctors carboplatin.
There was also an advantage for Imfinzi in patients with brain metastases, with the results from Caspian in this population topping those of Tecentriq in IMpower 133.
As predicted, no data were presented from another arm of the Caspian trial, which looked at Imfinizi combined with tremelimumab and chemo. Today Astra said that this data would not be available until 2020, following a recommendation from an independent monitoring committee that the event-driven trial continue to the final analysis.
Observers are looking for more information on the use of tremelimumab given that the drug has failed to perform in previous trials. There have also been doubts about the wisdom of adding the CTLA-4 product to combination therapy given the toxicity associated with the drug class.
For now Astra has scored a solid win in SCLC. While Imfinzi will not unseat Tecentriq in this setting, the drug continues to be an increasingly valuable player in the turnaround of the pharma giant's fortunes. According to consensus forecasts from EvaluatePharma, 2024 sales of the product are projected to exceed $3.6bn, making it the second most valuable asset in Astra’s portfolio, behind Tagrisso.