麻豆传媒

Treatment with a PD-L1 inhibitor held a survival advantage over single-agent chemotherapy for unfit non-small cell lung cancer (NSCLC) patients ineligible for platinum doublets, according to findings presented at the annual congress of the European Society for Medical Oncology.

In this exclusive 麻豆传媒 video, Nicholas Rohs, MD, of the Icahn School of Medicine at Mount Sinai in New York City, discusses the clinical impact of the IPSOS trial.

Following is a transcript of his remarks:

This was a study looking at atezolizumab, or Tecentriq, in patients with poor performance status -- ECOG 2, 3 -- or platinum-ineligible patients due to some sort of comorbidity -- kidney dysfunction, cardiovascular disease, etc.

So we know historically from the IMpower110 data that there was an overall survival benefit versus platinum doublet for patients with PD-L1-positive non-small cell lung cancer who maintain performance status of 1 or better. But unfortunately, about 40% or even more of our patients come into our clinic with a limited performance status of ECOG 2 or worse, and a lot of comorbidities. I'm assuming that most of you are seeing patients in the clinic with kidney dysfunction, cardiovascular disease, etc., that make it challenging to make the right choices for them as far as therapy.

So what they did was a phase III randomized global study of 453 patients. They randomized them in a 2-to-1 fashion to atezolizumab standard dosing versus what they called physician's choice of chemotherapy, but it was really a choice between Navelbine [vinorelbine] or gemcitabine [Gemzar]. No EGFR or ALK mutations were allowed. About 9% of the population had brain metastasis, which I applaud [the researchers] for [including]. And interestingly, no PD-L1 stratification was needed in this trial, though they did look at PD-L1 expression.

Really interesting population of patients when this is not a classically studied group, which I'm loving, and that's the strongest part of this study is that it was looking at this population, a huge unmet need. The median age was 75 years old, but 31% of patients were 80 or older. Unfortunately, 72% were male. There was a skew towards Caucasian patients. But still, again, a very interesting group of patients -- 83% had an ECOG of 2 or worse with 8% having an ECOG of 3.

So these were significantly physically impaired patients. And in the chemo arm, actually 52% of the patients had some form of PD-L1 expression, while only 42% in the IO [immuno-oncology/immunotherapy] arm [did]. So there may have actually been a little bit of a skew towards more PD-L1 positivity in that group.

And what we saw is really, the immunotherapy arm did do well. It had an improved overall response rate of about 16.9 versus 7.9 months. The median overall survival was numerically not dramatic. It was about 10.3 versus 9.2 months, with a good hazard ratio of 0.78. But what we saw is in the duration of response, 14 versus 7.8 months, so if they responded, they responded well and for a longer period of time.

The 2-year overall survival rates of 24.3 versus 12.4 are notable. So the patients who did respond did live longer, but I think a really important part of this trial was because these were functionally or medically limited patients, how was their tolerance of this therapy?

So we saw that actually grade 3/4 adverse events were less in the immunotherapy arm -- 16.3% versus 33%. We know that in the atezolizumab arm, they looked at quality-of-life metrics. And interestingly, while there was no definitive improvement in quality in life, which was disappointing, they did see that there was a prolonged time to deterioration. They used a standardized metric, and they saw things like chest pain were less common to happen upfront. And then things like anorexia and cough were less in this population. So some skewing towards an improvement in quality of life as well, or at least some specific symptoms.

Interestingly, again this was not a PD-L1-stratified study, and we saw benefit across all histologies, all PD-L1 expressions, and ECOG performance statuses. Maybe there is something a little bit different about the biology of this disease in this population, because there was actually a skew towards lower PD-L1 expressions or no PD-L1 expressions, which I thought was really interesting.

But there's always gotta be some critiques of a study. And I'd say for this one, my biggest critique is I don't find Navelbine or Gemzar to be my standard of care in this comparator in this population. I know this was an international study, so that may be the reason they chose these medications. They're a little bit more accessible.

But I think the leaving out of a drug like pemetrexed is a huge miss here. It's a really well-tolerated drug and worked very well in this patient population. I do think it would've been interesting to dig deeper into the PD-L1 story. This doesn't really address mutated patients. They did exclude the EGFR/ALK outpatients. So there's still an unmet need in this population.

And then the financial toxicity of these medications. We want to get our patients to therapy if we can, if we think it's going to help them. And this data is encouraging us that we may be helping prolong lives and keep good-quality lives of good tolerance of therapy on a single-agent immunotherapy. But these are very expensive drugs. So I think we have to continue to get more data sets like this to really specifically hammer down who we should be giving these therapies to.

There was a little bit of crossover in the study too. It wasn't allowed, but about 90% of the patients in the chemo arm ended up going over to an immunotherapy arm. Which actually strikes a little bit of an extra in favor of the immunotherapy arm.

So again, great dataset, very impactful. I think this is something we could start considering to apply in our clinics right now in the right patient population, with the good goals-of-care discussion, talking about where we're at.

But I do want to see more data in this space. I know there are some other ongoing trials in patients with limited performance status, and hopefully with better comparators. But really amazing dataset that I think is helping a very underrepresented population in clinical trials and giving us data to fall back on in clinic to make these right treatment decisions for our patients.

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