AstraZeneca announced Tuesday that the addition of the anti-CTLA4 antibody tremelimumab to the PD-L1 inhibitor Imfinzi (durvalumab) and standard-of-care (SoC) chemotherapy failed to demonstrate a significant improvement in overall survival (OS) in patients with extensive-stage small-cell lung cancer (SCLC) treated in the first-line setting. The drugmaker indicated that findings from the Phase III CASPIAN trial will be presented at an upcoming medical meeting.
The study randomised 805 patients with extensive-stage SCLC to receive Imfinzi in combination with etoposide and either carboplatin or cisplatin chemotherapy, or Imfinzi and chemotherapy with the addition of tremelimumab, versus chemotherapy alone. The trial's primary endpoint was OS in each of the two experimental arms.
Last year, the company reported that the study met one of its main goals, with Imfinzi plus SoC chemotherapy demonstrating a significant and clinically meaningful improvement in OS versus chemotherapy alone at a planned interim analysis. AstraZeneca noted Tuesday that top-line results from the final analysis confirmed a "sustained, clinically meaningful" OS benefit for patients given Imfinzi plus SoC chemotherapy.
José Baselga, executive vice president of oncology R&D at AstraZeneca, said "we have already received the first global regulatory approval for Imfinzi with etoposide plus either carboplatin or cisplatin," following clearance from Singapore's Health Sciences Authority. Imfinzi in combination with SoC chemotherapy is currently under regulatory review for the treatment of extensive-stage SCLC in the first-line setting based on the CASPIAN trial in the US, EU and Japan. The FDA has granted priority review to the filing, with a decision expected in the first quarter of 2020.
Earlier this month, AstraZeneca announced that in the Phase III DANUBE study, Imfinzi in combination with tremelimumab as a first-line treatment for patients with unresectable, stage IV bladder cancer failed to meet the primary endpoints of improving OS versus SoC chemotherapy. In October last year, the company reported that in the Phase III POSEIDON study, the triple combination of Imfinzi plus tremelimumab and chemotherapy was associated with significantly extended progression-free survival (PFS) over chemotherapy alone in patients with previously-untreated stage IV non-small-cell lung cancer (NSCLC).
The combination of Imfinzi and tremelimumab also previously failed to significantly improve either PFS or OS 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 in the Phase III MYSTIC trial. Further, 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 previously untreated patients with stage IV NSCLC.
For related analysis, see ViewPoints: Further evidence to suggest AstraZeneca's tremelimumab is a weak link, and ViewPoints: Bladder cancer setback moves tremelimumab into the very-last chance saloon.
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