麻豆传媒

Adjuvant atezolizumab (Tecentriq) significantly improved disease-free survival (DFS) compared with best supportive care after chemotherapy in patients with resected stage II-IIIA non-small cell lung cancer (NSCLC), according to the presented at the 2021 virtual .

In a recent 麻豆传媒 video, H. Jack West, MD, discussed the ongoing debate on whether a DFS endpoint is sufficient to change practice, noting that he was unsure if it would translate to overall survival. In this exclusive video, , of the University of Southern California Norris Comprehensive Cancer Center, has a different opinion.

Following is a transcript of his remarks:

Hi, my name is Jorge Nieva and I'm an associate professor of clinical medicine at the University of Southern California Norris Comprehensive Cancer Center. At this year's ASCO, we had a presentation from Heather Wakelee, MD, on the IMpower010 clinical trial. And this is the first positive clinical trial of adjuvant immunotherapy in lung cancer. Checkpoint inhibition has become, I think, the greatest advance in cancer medicine since targeted therapy, and has been a deliverance for so many lung cancer patients in particular.

I think I can -- and many of us can -- remember years ago when lung cancer was effectively a death sentence for patients. Particularly for those with late-stage disease, but even for those with early-stage disease. Stage for stage, had some of the lowest survival of any other tumor type. But that's changed now. And that's changed largely because of the development of checkpoint inhibitors.

We now are seeing long-term survivors from any of the checkpoint inhibitors that are out there and approved, and I think there may be five or more -- it's easy to lose track, there's so many of them. We have pembrolizumab, nivolumab, atezolizumab, now cemiplimab, durvalumab. And the exciting thing about all of these agents is that they produce Kaplan-Meier curves that are flat, with plateaus in the 20% to 40% range where patients just stopped dying of the disease. And where the plateau sits depends on factors in the trial, PD-L1 status of the patients.

But IMpower010 is the first adjuvant trial and it enrolled over 1,000 patients. And what we see is an improvement in disease-free survival in this preliminary analysis as it was presented at ASCO. We see in the PD-L1 >1% population, a hazard ratio of 0.66. And in all comers, a hazard ratio of 0.79 for disease-free survival.

The overall survival data are not mature. And herein lies the debate and all the back and forth on Twitter, which really comes down to what endpoint is needed in order to justify the use of a new drug in the adjuvant setting in lung cancer. For many oncologists, it still has to be overall survival. And for those of us who trained in the era where lung cancer was a universally fatal disease, I think that made a lot of sense. We needed to see overall survival in order to justify that a drug really worked and that it was really necessary.

Now, none of the other fields of medicine actually do that. Cardiology has been using combined endpoints of survival plus reinfarction plus revascularization and a host of other things. And that's been OK and they take care of sick people, too. But in oncology, we've had this fixation for years that if it's not overall survival, it doesn't count.

But I think we should start being different and disease-free survival is an acceptable endpoint, in my mind. Patients are now living longer and they don't want to relapse. Relapsing with your cancer is really a terrible thing. It makes it so you can't plan in the future. Makes it so that you have to take new treatments that can be frightening, sometimes involving chemotherapy again. I don't think patients want to relapse. And I think if we have the ability to avoid relapse, we should.

Now the counterpoint to that is that since these drugs actually work in the metastatic setting and prevent death, perhaps we don't need to give them early, perhaps we can now wait until people relapse. You know, that was never the case with chemotherapy. Chemotherapy only had a potential to keep patients from dying if given early, and in the metastatic setting it always prolonged survival, it didn't cure patients.

But I think for these patients the need to not relapse outweighs that requirement. And while the toxicity of immunotherapy drugs is not trivial, it is certainly less than chemotherapy. And I think in the end, for our patients, having more options is better. This doesn't mean that every patient needs to get checkpoint inhibitors in the adjuvant setting. But if we don't accept that this is an option and we don't have these drugs available to use in the adjuvant setting, then we can't have that conversation with the patients.

And in the end, I think it's better to have more options. It's better to put the patient in the driver's seat as to what is acceptable and what they want to do with their care. So, in the end, I fall down on the side of I think disease-free survival is an acceptable endpoint, and that really is the controversy with this trial. And for me, I think this is very exciting and I think fewer patients relapsing is good. And having more patients who come into the office happy because they're in for their surveillance scans and they look great; well, I really love those visits. And I think the more of those we have, the better.

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