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Dr. Moore: 
We've heard a lot of new data around the use of HER2 antibody-drug conjugates for patients with advanced solid tumors. What does the future hold in terms of using this treatment and practice?  

This is CME on ReachMD, and I'm Dr. Kathleen Moore. Joining me today are Dr. Susana Banerjee and Dr. Shubham Pant.  

Susana, we've seen remarkable results from the Destiny-PanTumor study in gynecologic cancers, but just as a summary, about a 50% response rate across the 3 cohorts. And this has led to NCCNlistings for T-DXd for recurrent cervical and endometrial cancer, not quite yet ovary. From a clinician standpoint, what do you think of this? How are you thinking about incorporation of T-DXd, and as this rolls into the treatment paradigm, what should we be thinking about as practitioners? 

Dr. Banerjee: 
Thank you, Dr. Moore. I think the first aspect is HER2 testing in clinical practice. So we need to enable our teams totest all patients with gynecological cancers and also to redefine the expression across the tumors for the relevant tumor type. The next important point is about how do we sequence and integrate these drugs in endometrial cancer and cervical cancer, for example, with immunotherapy, in the pathway lenvatinib and also tisotumab vedotin, for example, in cervical cancer. And in ovarian cancer, where there's lots of drugs in this area, there are certain ovarian cancers that have limited efficacy and limited options, such as mucinous ovarian cancer, where HER2 expression is notable in around 15%, and I'd very much like to highlight the use in these groups. And then finally, it's about patient safety. We need training and educating our teams and patients on pneumonitis and interstitial lung disease so that more patients can benefit from these treatments for longer safely. 

Dr. Moore: 
Thank you for that. I'm going to turn to Shubham. We've been very excited in a gynecologic oncology standpoint and others, especially urologic, but for pancreatic cancer, we're a little disappointed with Destiny-PanTumor. Can you just touch on the GI tumors in this important study and sort of how you're framing these results? 

Dr. Pant: 
Thank you so much, Katie. So pancreatic cancer, you are right, disappointing results. However, it's in context. Pancreatic cancer is a hard-to-treat cancer. There's a lot of desmoplastic stroma. About 90% of patients have KRAS mutations. Also, when you look at the data, majority of the patients across the board in the DESTINY study, the higher benefit was for patients with IHC 3+. Now IHC 2+ also benefited, but it was more with IHC 3+, and really very few patients with pancreatic cancer had IHC 3+ expression. So it could have multiple factors in play.  

However, we were really enthusiastic about the biliary tract cancer results in which for IHC 3+ the overall response rate was 56%. So that's heartening. So a little bit disappointing in one tumor in GI but very heartening in another tumor in GI. 

Exactly. So end on a high note. Thank you. So that is some food for thought as we look towards the future.  

Dr. Moore: 
Thank you for that. I'm going to turn to Shubham. We've been very excited in a gynecologic oncology standpoint and others, especially urologic, but for pancreatic cancer, we're a little disappointed with Destiny-PanTumor. Can you just touch on the GI tumors in this important study and sort of how you're framing these results? 

Dr. Pant: 
Thank you so much, Katie. So pancreatic cancer, you are right, disappointing results. However, it's in context. Pancreatic cancer is a hard-to-treat cancer. There's a lot of desmoplastic stroma. About 90% of patients have KRAS mutations. Also, when you look at the data, majority of the patients across the board in the DESTINY study, the higher benefit was for patients with IHC 3+. Now IHC 2+ also benefited, but it was more with IHC 3+, and really very few patients with pancreatic cancer had IHC 3+ expression. So it could have multiple factors in play.  

However, we were really enthusiastic about the biliary tract cancer results in which for IHC 3+ the overall response rate was 56%. So that's heartening. So a little bit disappointing in one tumor in GI but very heartening in another tumor in GI. 

Dr. Moore: 
Exactly. So end on a high note. Thank you. So that is some food for thought as we look towards the future.  

I want to remind our listeners that we have a whole little segment on metastatic bladder cancer, so we're not going to touch on that today because it really deserves its own discussion with all of the recent positive data in this disease, which, kind of like gynecologic cancers, has gone without big advancements in a long time. 2023 was a big year. So please join Dr. McGregor for that series if you're interested in bladder cancer.  

There's a number of other HER2-targeting ADCs in the pipeline with emerging data, BNT323, disitamab vedotin, just to name a few. We will see more data coming out across solid tumors that will put a lot of this into context. There's a lot of continued work into the biomarkers, as referenced by Dr. Banerjee, as well as CTD and other markers to really identify who will benefit best from this new class of agents.  

But that's all the time we have today. Thank you to Dr. Susana Banerjee and Dr. Shubham Pant for joining me. Thank you to our audience. And this is CME on ReachMD. Thank you. 

Dr. Pant: 
Thank you. 

Dr. Banerjee: 
Thank you.  

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