WCLC Sept 2021 | POSEIDON: durvalumab +/- tremelimumab + chemo in 1L mNSCLC

At World Lung 2021, we presented the final results of the POSEIDON study, which was a frontline non-small cell lung cancer trial in which patients with newly diagnosed disease were randomized to receive durva-chemo, durva-treme-chemo, or chemotherapy alone. After four cycles of chemotherapy, patients in the immunochemotherapy arms went on to just receive maintenance durva. Patients that had non-squamous cancers could also receive maintenance pemetrexed. Patients in the durva-treme arm could receive a fifth dose of tremelimumab, so one additional dose. And then, patients that were randomized to chemotherapy alone could get up to six cycles of treatment. So it’s a little different than other trials evaluating immunotherapy added to chemotherapy, such as CheckMate 9LA, for example, or KEYNOTE-189 and KEYNOTE-407.

The headline results of the trial were that it improved progression-free survival for patients that received durva-chemo versus chemo, as we’ve come to expect. It also resulted in a trend towards improved overall survival for patients who received durva-chemo versus chemo. Interestingly though, the key secondary endpoints that were evaluated showed an improvement in both PFS and overall survival for patients that received durva-treme-chemo versus chemo. So I think the analysis from the trial show that immunotherapy added to chemotherapy improved survival. In this particular trial, the addition of anti-CTLA-4 to chemo and PD-1 was both safe, tolerated, and prolonged survival in most of the subgroups that were evaluated, in particular for patients that had high levels of PD-L1, non-squamous patients, and interestingly and maybe predictably, for patients with PD-L1 low cancers, PD-L1 low tumors. Those are patients where we don’t feel satisfied with a PD-1 strategy alone. And so, we’re in the habit of adding chemotherapy to that, to result in less early disease progression while the immunotherapy gets going. And it seems like the anti-CTLA-4, in this case, helped just a little bit more.

Will this trial result in regulatory approval? I know that those discussions are underway. Don’t know the answer to it yet, but it would be the first approval of tremelimumab in any setting, which would be, I think, an exciting contribution from this trial, although much of the discussion since the presentation has been whether the world really needs another high-cost quadruplet, and certainly, you could debate both sides of that question. I think, in general, it shows that patients have lots of options in the frontline for the treatment of their lung cancer. And so, the critical next step is going to be biomarkers or molecular signatures or other sorts of signatures that help us figure out who should get what and how to better parse out that frontline lung cancer space for patients that are oncogene driver-negative.