Melissa Johnson, MD, Tennessee Oncology, Nashville, discusses an overall survival (OS) update from the POSEIDON trial after a median follow-up of approximately 4 years, showing a durable long-term OS benefit with adding a limited course of tremelimumab to durvalumab and 4 cycles of chemotherapy for patients with metastatic non-small cell lung cancer (NSCLC).

This update was presented at the 2022 ESMO Annual Meeting.

Transcript:

Hi, I'm Dr. Melissa Johnson. I'm the director of the Lung Cancer Research Program at Sarah Cannon, and a medical oncologist with Tennessee Oncology and OneOncology.

At ESMO 2022, I presented the overall survival update from POSEIDON, a randomized phase 3 trial that combined chemotherapy with immune therapy. This was the four-year follow-up data. Remember that POSEIDON was a randomized phase 3 trial for newly diagnosed NSCLC patients without EGFR or ALK alterations.

They were randomized to one of 3 treatment arms, either platinum-based chemotherapy for up to 6 cycles or platinum chemotherapy and durvalumab once every 3 weeks for 4 cycles, followed by durvalumab once a month until progression, or chemotherapy plus durvalumab and tremelimumab once every 3 weeks for 4 cycles, followed by a fifth dose of tremelimumab at week 16, and then durvalumab once a month maintenance until progression.

Patients were randomized 1:1:1, and the primary end points of the trial were PFS and overall survival for patients treated with durva-chemo vs chemo, with alpha controlled secondary end points, PFS and overall survival for patients treated with durva-treme-chemo vs chemo.

Now, at the World Lung meeting in 2021 we have heard the primary analysis, the trial was a positive trial showing improved overall survival for patients that were treated with durva-treme-chemo vs chemotherapy. And this was seen across a number of subtypes with more follow up data.

Now a median of 4 years that overall survival benefit persists. And as we look at the forest plot across all of the different subgroups that were analyzed in the trial, we see a gentle shift to the left for patients treated with durva-treme-chemo vs chemotherapy as compared with durva-chemo vs chemotherapy. The addition of tremelimumab does seem to add a little bit in terms of overall survival benefit.

The places in this trial where that overall survival benefit were the most pronounced were in patients with PD-L1 low and PD-L1 no expressing cancers, and that's good because those are patients in whom we're looking for other options beyond just PD-1 chemotherapy. Also, non-squamous patients treated in this trial had a pronounced overall survival benefit with durva-treme-chemo vs chemo.

With 4 years median follow up the hazard ratio was 0.75 in favor of the quadruplet, and that means that 25% of patients were alive at 3 years. All of a sudden, this POSEIDON data can be put alongside the CheckMate-9LA data, the KEYNOTE-189, and the KEYNOTE-407 data—all of the hazard ratios in the mid seven range, all of the median survival at 3 years being around 20% to 25%. Although the POSEIDON trial was the last to report, it was enrolled along with all the others.

Now the main criticism of POSEIDON has been like, why do we need another 4-drug regimen? We have nivo-ipi-chemo and we have pembro-chemo for all patients. Isn't that enough? And while that's true, this does represent an option that is particularly effective for patients that have hard to treat cancers.

There was a subset analysis that was initially reported at World Lung in 2022 by Professor Solange Peters, and it was updated at this ESMO meeting showing that patients that had KRAS mutations, patients that had STK11 mutations and patients with keep alterations all had improved overall survival when they were treated with durva-treme-chemo vs chemotherapy. And that was not seen for patients that got durva-chemo vs chemotherapy.

As we start to pick apart the frontline and decide which patients are best treated with chemo-immunotherapy, which patients can get immunotherapy alone, there is a small group of patients that are still very difficult to treat. And so, as I walk away from ESMO 2022 and consider the POSEIDON data, I wonder if one of the places that this durva-treme-chemo regimen will find a place is in these hard to treat patients.

Source:

Johnson ML, Cho BC, Luft A, et al. Durvalumab (D) ± tremelimumab (T) + chemotherapy (CT) in 1L metastatic (m) NSCLC: Overall survival (OS) update from POSEIDON after median follow-up (mFU) of approximately 4 years (y). Presented at ESMO Congress; September 9-13, 2022; Paris, France. Abstract LBA59.