Metastatic Colorectal Cancer: Future Directions in Care

EP: 1.Overview of Molecular Testing in Metastatic Colorectal Cancer (mCRC)

EP: 2.Role of Tissue Versus Circulating Tumor DNA in Molecular Testing in mCRC

EP: 3.Circulating Tumor DNA to Guide Treatment Selection for mCRC

EP: 4.Challenges With Molecular Testing in Metastatic Colorectal Cancer

EP: 5.First-Line Treatment Options for mCRC

EP: 6.Trastuzumab Deruxtecan in HER2+ mCRC

EP: 7.HER2+ mCRC: Managing Adverse Events Associated With Antibody Drug Conjugates

EP: 8.Role of Tucatinib in HER2+ mCRC

EP: 9.Importance of Identifying HER2 Status in Metastatic Colorectal Cancer

EP: 10.Combination Therapy in BRAF-Mutated mCRC: The BEACON CRC Trial

EP: 11.Combination Therapy in BRAF-Mutated mCRC: The BREAKWATER Trial

EP: 12.Other Combination Strategies in BRAF-Mutated Metastatic Colorectal Cancer

EP: 13.Overview of Immune Checkpoint Inhibitors in Metastatic Colorectal Cancer

EP: 14.Clinical Trials in Metastatic Colorectal Cancer: Combination IO Therapy

EP: 15.Combination IO/TKI Strategies in Metastatic Colorectal Cancer

EP: 16.Novel Combination Strategies in mCRC: The STELLAR-303 and SUNLIGHT Trials

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EP: 17.Metastatic Colorectal Cancer: Future Directions in Care

Transcript:

Kristen K. Ciombor, MD: I think this has been a really rich and informative discussion. I want to thank my fellow panelists, but before we conclude I wanted to get everyone’s takeaway from our discussion tonight. What is one thing you would want our viewing audience to take away from our discussion? I’ll start with you, Dr Hubbard.

Joleen M. Hubbard, MD: I was going to use my canned answer like, “Make sure you’re doing next-generation sequencing on all tumors.” But actually, I am going to use something I learned in this session. Dr Raghav made me think about how we approach first-line metastatic colorectal cancer [mCRC], and the analogy that it would be malpractice if we were in breast cancer and proceeded with treatment without our biomarker information, or lung cancer. Maybe we do need to change our mindset of how we approach first-line mCRC and realize it’s really important to have these biomarkers before we embark on treatment, to get patients enrolled into the first-line trials that may show we’re going to improve outcomes in the long term. Thank you, Dr Raghav.

Kristen K. Ciombor, MD: Excellent. We’re always learning from each other, aren’t we?

Joel R. Hecht, MD: We’ll be quoting that, yes.

Kristen K. Ciombor, MD: Dr Kasi, what about you?

Pashtoon M. Kasi, MD: I couldn’t agree more. Building on the same story, I think until we get drugs that work for all patients with CRC, which they don’t, but advances are coming in these subsets. To truly identify who may benefit from whatever precision medicine or targeted therapy approach, HER2 has a new approval as of yesterday; the only way we’ll identify these patients is through testing. I want to reiterate the fact that we need to be able to test and identify the patients where we can make a bigger difference.

Kristen K. Ciombor, MD: Great point. For me, as exciting as seeing these different subsets and seeing how actionable they are becoming is really exciting, but also frustrating because you see only 2% of your population has a particular actionable mutation. But I think it behooves us to keep looking for those and treating them accordingly, and also encourage our cancer centers and our community sites that help identify these patients to continue the effort, continue the clinical trials, looking at very thoughtful ways to combine these agents for the good of our patients. Dr Raghav?

Kanwal P. Raghav, MD: I think you guys bring up very important points. I always like quoting [the line] “miles to go before I sleep.” I think the lesson is, we talk about clinical trials, we love discussing evidence. But this is not going to be possible unless and until we have patients for trials. One lesson to be learned here is we’ve made a lot of strides, but none of these strides—barring exceptions of MSI [microsatellite instability]-high and immunotherapy—none of these strides are something that we can be so proud of that we are like OK, the work is done, we are finished.

Kristen K. Ciombor, MD: Correct.

Kanwal P. Raghav, MD: Before you treat any patient on any treatment, in any line in mCRC, the first question you should always ask is, is there a trial I can put this patient on? And from a patient perspective, I think we should empower our patients to ask for clinical trials at every stage of decision-making. Those clinical trials and participation will be the greatest inflection point that will help us combat this disease.

Joel R. Hecht, MD: What I would take away is that Dr Kasi and Dr Raghav brought up really good points about the sort of ferment having to do with testing. Remember how long it took in breast cancer, for example, with HER2 testing? People argued about that literally for a decade. I think this is even harder because the technologies are changing, there are multiple places where we do this. I think it’s a really exciting time. But back to what you were saying about putting people on trials, this is not something with a 20-patient trial or 100-patient trial. We’re talking about national trials in order to do this because, at the end of the day, the clinician’s going to say, “What do I do now? What do I order, and what do I do now?”

The other thing is, I think you brought up a really good point. It’s great when we have a hazard ratio of 0.8, but when we have a PFS [progression-free survival] of 8 months, it’s not that long in the grand scheme of things. What I’m encouraged about is, I hope the TKI [tyrosine kinase inhibitor] plus IO [immunotherapy] has some tail of the curve. I hope bot [botensilimab] and bal [balstilimab] also have some tail of the curve because that’s what our patients want. Patients don’t want an 8-month progression-free survival. They really want a tail of the curve.

Kristen K. Ciombor, MD: Yes, absolutely, very well put. Thank you so much. Thank you to my panelists. And to our viewing audience, thank you for joining us. We hope you found this OncLive Peer Exchange®discussion to be useful and valuable to the treatment of your patients with CRC.

Transcript edited for clarity.