Day 1: Top Takeaways From ASCO26

Today I'll be reviewing three abstracts, including a follow-up from the E D three oh two study. I think we're all aware of that one in urethelial carcinoma. Potential new treatment option for patients with PDL1 positive advanced non small cell lung cancer, and a novel psychosocial digital application that improves fatigue and distress in patients with multiple myeloma.

Why don't we begin with abstract forty five oh seven? Now this is an update of the EV three hundred two study. Now just as a refresher, Enfortimavvidotin is actually a antibody drug conjugate that's really revolutionized care across multiple settings in urethelial carcinoma. Having said that, the EV three hundred two data is actually the first setting in which we saw significant activity in a phase three trial with use of this agent in combination with Pemberism.

The investigators here, led by Tom Powells, updated three and a half years of median follow up and had some really interesting subgroup analyses as well. Gister's refresher in this trial patients were randomized in a one to one fashion if they had metastatic previously untreated urethelial carcinoma gen fortomab Vidotin in combination with Pembrolizimab.

Or what's really been heralded as a standard for several decades, which is platinum based chemotherapy, either it's platinum or carboplatin, which I'm cytobe. Now with forty two point eight months of median follow-up, what we saw here was a survival advantage that seemed to consistently favor in PortaMab with Pembrolizimab.

If we look at the landmarks at forty-two months, the survival rate was eighty-three percent. Now this is just remarkable when we consider what outcomes associated with the disease used to look like. The median time to complete response was actually about four and a half months in the context of this trial. And the data also adds several elements related to conversions from pathological partial responses to complete responses.

And I do think that this adds really an air of further intrigue to the data that we've already seen around the combination of Inforta mab with Pemberless mab in this setting. Two thirds of patients achieving a complete response converted from an initial partial response, suggesting that perhaps after initial response, cure is still achievable.

And in this particular clinical trial, patients were randomized in a one to one fashion in this study to receive either SAC TMT with pembrolizimab versus pembrolizimab alone. Now importantly, the patients who are eligible for this study had treatment naive locally advanced or metastatic non-smal cell lung cancer. They did not have EGFR alkyl alterations, and they did have positive PDL1 expression.

So the primary endpoint in the study was progression free survival, as was assessed by Blinded Independent Central Review, and a key secondary endpoint was overall survival. What they saw in this study is that with a median fall up of ten and a half months, progression free survival by independent review was significantly longer in the SAC TMT group.

The estimate was not reached as yet in that subset versus five point seven months with Pembrolizimab alone. This amounted to a hazard ratio of zero point three five with a significant P value. There did seem to be a favorable trend in terms of overall survival, although the authors note that it wasn't quite the right time. The overall survival data was not mature. Having said that, the hazard ratio was zero point five five in this context.

If we look at prespecified histologic subgroups, and we're always interested in that distinction between non-squamous and squamous histology, we saw here a hazard ratio for benefit with respect to PFS of 0.28 in those patients that were non-squamous. And those patients that were sclamous had a hask ratio benefit of zero point four four.

Now importantly if we think to the toxicities that we incur with this regimen, there were significant neutrophil count decreases, anemia and stomatitis, and we might potentially anticipate that with drugs of this nature. To the investigators' knowledge, they purport that this is really the first time that we've seen a significant pavation free survival advantage with the combination of antibody drug conjugate with pembzimab versus pembolismab alone.

It's exciting to see how this regimen will develop and I know all eyes are gonna be on the final survival analyses from these data.

And we've moved from doublet therapies to triplets to quadruplets, and there's even some discussion in clinical trials of quantum therapy for this disease. But having said that, there's certainly a number of toxicities that patients incur and a significant need to help in managing those toxicities with various interventions.

So this Thrive MM or multiple myeloma study looked at a self guided psychosocial digital application really with the intent of improving quality of life, fatigue, and psychological distress. This was a single center study, so keep that in mind. Which used the Thrive MM model versus usual care. Patients had to have newly diagnosed multiple myeloma. They also could have potentially had relapse disease receiving second or third line therapy, and also they could have been on maintenance.

They were stratified by this line of therapy, and they were randomized one-to-one as noted earlier to receive either usual care or drive MM. And ultimately what was found in the context of the study. With really a a very healthy number of patients enrolled, one hundred and twenty out of two hundred and three eligible patients, what they found was that there seemed to be some degree of improvement in fatigue. They seemed to have a decrease in depressive symptoms.

They however did not see that there was a significant improvement in quality of life, and that's quite notable. Having said that, with hopefully what might amount to a low cost intervention, it it may still be of work to further explore whether or not something like Drive MM could be incorporated in clinical practice, fatigue and Depressive symptoms are are certainly things that, you know, we want to focus on in terms of the day to day lives of our patients.

Well, there you have it. Thank you so much for tuning into the Asco Daily News Podcast. You can access the abstracts mentioned today in the transcript and join me again tomorrow to hear more top takeaways from ASCO twenty six. An awesome meeting. And if you enjoyed this episode, be sure to hit follow on your favorite podcast app and leave a review.