AstraZeneca on Monday announced results from the Phase III POSEIDON study showing that the addition of the PD-L1 inhibitor Imfinzi (durvalumab) to chemotherapy significantly improved progression-free survival (PFS) in patients with previously-untreated stage IV non-small-cell lung cancer (NSCLC) versus chemotherapy alone. Moreover, the triple combination of Imfinzi plus AstraZeneca's anti-CTLA4 antibody tremelimumab and chemotherapy was also associated with significantly extended PFS over chemotherapy alone.
José Baselga, executive vice president of oncology R&D at AstraZeneca, noted that "clinical benefit was observed in a trial population that included a high proportion of patients with squamous disease and multiple choices of chemotherapy regimens." He suggested "the potential to add tremelimumab to Imfinzi and chemotherapy may present an important treatment approach in this challenging setting."
The latest results contrast with earlier findings from the Phase III MYSTIC trial, in which first-line use of Imfinzi plus tremelimumab had failed to significantly improve PFS in patients with EGFR and ALK wild-type, locally-advanced or metastatic NSCLC who express PD-L1 on at least 25% of their cancer cells. The study later also found that neither Imfinzi monotherapy, nor its combination with tremelimumab, was any better than chemotherapy at extending overall survival (OS) either.
More recently, AstraZeneca announced that Imfinzi plus tremelimumab also failed to hit the main OS goal in the Phase III NEPTUNE study, which compared the combination against standard chemotherapy in newly diagnosed NSCLC patients (for related analysis, see ViewPoints: Keytruda rivals running out of lifelines in front-line lung cancer).
POSEIDON included patients with either squamous or non-squamous disease and the full range of PD-L1 expression levels, but not those with EGFR or ALK gene mutations. Participants in the treatment groups received either Imfinzi with four cycles of chemotherapy once every three weeks, or Imfinzi plus tremelimumab, followed by maintenance therapy, which consisted of either Imfinzi or Imfinzi plus one dose of tremelimumab on a once-every-four-week dosing schedule. Meanwhile, patients in the control group were administered up to six cycles of chemotherapy.
AstraZeneca said the safety of Imfinzi in the POSEIDON trial was consistent with its known profile. Further, the triple combination delivered a "broadly similar safety profile" to Imfinzi plus chemotherapy, and did not have higher discontinuation rates.
POSEIDON is evaluating the co-primary endpoints of PFS and OS for Imfinzi plus chemotherapy, while key secondary goals will look at PFS and OS in the triple combination regimen. AstraZeneca said it will submit the results for presentation at an upcoming medical meeting and plans to share them with health authorities as well. It added that the trial will continue to assess OS with data anticipated in 2020.
Analyst Sam Fazeli of Bloomberg Intelligence remarked that "while a positive PFS bodes well for the OS, unless there's significant crossover, only the detailed data could decipher if Imfinzi could win a place in the competitive first-line setting." Meanwhile, analyst Louise Chen of Cantor Fitzgerald indicated that she would also wait for additional data before drawing conclusions from the POSEIDON results, saying "if the data end up being competitive to Merck & C.'s Keytruda (pembrolizumab) trials, this positive-sounding safety data could support true commercial viability for the triple combination."
Last week, AstraZeneca reported that Imfinzi generated $412 million in sales during the third quarter, compared with $187 million in the prior-year period.
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