OS Promising for Adjuvant Atezolizumab in PD-L1-Positive NSCLC

Longer follow-up in the IMpower010 trial further cemented the value of atezolizumab (Tecentriq) in treating stage II-IIIa non-small cell lung cancer (NSCLC) in patients with tumors expressing PD-L1. The new data were presented at the recent World Conference on Lung Cancer (WCLC).

In this exclusive MedPage Today video, Nicholas Rohs, MD, of the Icahn School of Medicine at Mount Sinai in New York City, discusses the updated findings.

Following is a transcript of his remarks:

We really had a great focus on early-stage tumors, and one of the updates that we got at this conference was the IMpower010 trial. This was the 5-year overall survival update. So, consistent with our new fast-paced field of oncology, studies are being released kind of piecemeal as the information comes out because we want to know this data as soon as possible.

So we’d already heard about the DFS [disease-free survival] hazard ratio of 0.79 in PD-L1-positive tumors, that hazard ratio was dropping down to 0.66. So we already knew disease-free survival was impactful with adjuvant atezolizumab. And that’s what this trial was. This was adjuvant atezolizumab for patients who had a surgically resectable or operable stage Ib-IIIa non-small cell lung cancer. This has been approved as a therapy as of October of last year based off of the DFS data, but it’s really nice to see this overall survival data.

So again, these were early-stage IIb-IIIa patients that had ability to check their PD-L1 expression. And there were about a 1,000 patients randomly assigned to either 1,200 mg of atezolizumab every 21 days versus best supportive care. And while disease-free survival was the primary outcome, overall survival was a key secondary endpoint. And this was at a median follow-up of about 46 months.

And we saw that the overall survival was definitely skewing towards positivity. The hazard ratio was 0.71 for all-cause mortality. But really the great overall survival benefit was predominantly in PD-L1-positive patients or PD-L1-high-positive patients, meaning greater than or equal to 50%. And the hazard ratio in that population was 0.43. And then the benefit in those who were PD-L1-negative unfortunately did not show similar benefit. And really the stage II-IIIa disease was not as impactful for these low immune expressors.

And we also have to mention that atezolizumab, while a very well-tolerated drug, is not a completely benign drug. So, we saw that in the atezolizumab arm that adverse events were about twice as likely in this patient population. And some of these were serious and/or life-threatening events.

So, Dr. [Benjamin] Besse gave a really good commentary about this trial afterwards. There’s still some things that we’re trying to learn. We want to see this overall survival data mature some more. But we also want to understand things about what are the crossover rates in these populations, which patients who were randomized to best supportive care eventually did get immunotherapies. And there’s some concern that maybe some of the subgroups in the control arm over-performed. So we want to see this data mature, we want to be able to get more granular in the data, because we really want to make sure we’re using this in the right population.

But for right now, I think this data really supports that in PD-L1-high-expressing patients that are greater than or equal to 50%, this is probably the right choice for those patients who have not gotten any neoadjuvant therapy. And really much more of a decision discussion about the lower immune expressors and if it’s valuable, and it’s probably not the right choice for those patients who have no immune expression on their tumors.

But this is still approved at least in the United States and PD-L1-positive patients after surgery. So this is the discussion we’re going to have to continue to have with our colleagues as the data matures, but a really exciting update for the IMpower010 trial.