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Additional Advances in Esophagogastric Cancer Research and Clinical Trials With Jaffer Ajani, MD

Last year, Jaffer Ajani, MD, Professor in the Department of Gastrointestinal (GI) Medical Oncology at MD Anderson Cancer Center, served as co-chair of i3 Health's Virtual Tumor Board, Building Comprehensive Care Plans in Esophagogastric Cancers, along with Lei Zhao, MD, PhD, Assistant Professor of Pathology at Brigham and Women's Hospital, and Kelly Rone, DNP, RN, AGNP-c, Advanced Practice Nurse at the Mayo Clinic. With numerous developments in the field occurring since recording the activity, Dr. Ajani sat down with Oncology Data Advisor to provide an update on the evolving field of esophagogastric cancer research and advances to look forward to in the coming years.  

Oncology Data Advisor: Welcome to this Oncology Data Advisor interview. I have the pleasure of speaking with Dr. Jaffer Ajani from MD Anderson Cancer Center. Last year, Dr. Ajani served as one of the three co-chairs of i3 Health's Virtual Tumor Board, Building Comprehensive Care Plans in Esophagogastric Cancers. Today, he's here to share some additional updates that have occurred in this field since the activity was launched. Dr. Ajani, it's a pleasure to have you on today.

Jaffer Ajani, MD: Hi, thank you so much. I think there are lots of changes, and there are also changes in the attitude towards how we should approach esophageal cancers, especially esophageal adenocarcinoma and squamous carcinoma of the esophagus. Fortunately, as you well know, the landscape has been changing, and we haven't stopped yet because there are many other things about to happen.

I think one new emphasis is on biomarkers. One way to consider that is what are called agnostic approvals, a list which is expanding. That list is really relevant to every patient you see in your clinic, because unless you test for those biomarker-driven agnostic approvals, you're not going to find out. In other words, if you don't check it, you'll never know. That has become very important in patient management.

The second thing is that the biomarkers that were traditional in gastroesophageal adenocarcinoma have expanded now, and their role has changed. For example, microsatellite status testing is now recommended for every patient. Before, it was limited to patients with metastatic disease, but now we know that even in a localized patient who's about to have surgery or about to have preoperative chemotherapy, if their tumor is microsatellite instability (MSI)–high, we are not recommending chemotherapy or surgery for them. We're actually recommending immunotherapy. We need to advertise this in a professional manner to all of our colleagues so that patients get appropriate treatment. Some of these patients can entirely avoid surgery, which we had never heard of before, but now we know that 30% to 40% of patients don't even need surgery if they have an MSI-high tumor. So, that's one development.

Then the approval of pembrolizumab (pembro) in this space has added another programmed cell death protein 1 (PD-1) inhibitor. Patients with gastroesophageal junction (GEJ) cancer have pembro plus chemotherapy. Before, we had approval only for chemotherapy and nivolumab (nivo), so that's a change. Along the same lines, there's a drug called tislelizumab. This is another PD-1 inhibitor by a company called BeiGene, and they got approval for squamous carcinoma in the second line for those patients who have not had a PD-1 inhibitor before.

As far as what's on the horizon, we are all waiting for claudin-18.2 as a target. That's a brand-new biomarker that is coming to upper GI tumors. That will also help to treat a subset of patients that we haven't treated before. The drug is zolbetuximab. We don't know when it will be approved, but all the data have already been reviewed by the FDA from two trials, SPOTLIGHT and GLOW. I think that will be an exciting new development in the area. Plus, it will be a challenge because every one of us will have to learn to check for claudin-18.2, which we don't even think about today.

In the human epidermal growth factor receptor (HER2) space, there are additional results on KEYNOTE-811. There is a new facet to HER2-positive untreated advanced disease patients. What the results show is that if the programmed death ligand 1 (PD-L1) is negative, there's no advantage to adding pembrolizumab. If you recall, the FDA had approved the addition of pembrolizumab a couple of years ago based on interim data, and PD-L1 expression was not specified. Now, the FDA has changed the approval label, and it specifically mentions that if the tumor is PD-L1–negative, you should not add pembrolizumab because they actually do worse. If PD-L1 is positive, which fortunately is the case for the majority of patients, pembrolizumab can prolong progression-free survival, but not overall survival.

So, I think these are the changes in upper GI tumors. Once again, I'll just emphasize that it's no longer like 10 years ago when patients came into your clinic, you gave chemotherapy, and you checked HER2 only. Now you have to check all these biomarkers and adjust the treatment. That doesn't mean you cannot start chemotherapy, because a lot of these patients are symptomatic. You've got to get going with chemotherapy, but as soon as the biomarker results are available, you can adjust.

Oncology Data Advisor: Amazing. Well, thank you so much for coming on the podcast today and sharing this research with us. It was so wonderful to hear about all of the latest progress in the field. To everyone listening, be sure to visit the i3 Health website if you'd like to view Dr. Ajani's full CME/NCPD activity and claim credit. Thank you again.

Dr. Ajani: Thank you, take care.

About Dr. Ajani

Jaffer Ajani, MD, is a Professor in the Department of Gastrointestinal Medical Oncology at the University of Texas MD Anderson Cancer Center. He specializes in the treatment of gastrointestinal cancers, including gastric, esophageal, and colorectal cancers. He has authored or coauthored numerous publications focusing on gastrointestinal cancer research.

For More Information

Shitara K, Lordick F, Bang YJ, et al (2023). Zolbetuximab plus mFOLFOX6 in patients with CLDN18.2-positive, HER2-negative, untreated, locally advanced unresectable or metastatic gastric or gastro-oesophageal junction adenocarcinoma (SPOTLIGHT): a multicentre, randomised, double-blind, phase 3 trial. Lancet, 401(10389):1655-1668. DOI:10.1016/S0140-6736(23)00620-7

Shah MA, Shitara K, Ajani JA, et al (2023). Zolbetuximab plus CAPOX in CLDN18.2-positive gastric or gastroesophageal junction adenocarcinoma: the randomized, phase 3 GLOW trial. Nat Med, 9(8):2133-2141. DOI:10.1038/s41591-023-02465-7

Jangigian YY, Kawazoe A, Bai Y, et al (2023). Pembrolizumab plus trastuzumab and chemotherapy for HER2-positive gastric or gastro-oesophageal junction adenocarcinoma: interim analyses from the phase 3 KEYNOTE-811 randomised placebo-controlled trial. Lancet, 402(10418):2197-2208. DOI10.1016/S0140-6736(23)02033-0

Transcript edited for clarity. Any views expressed above are the speaker's own and do not necessarily reflect those of Oncology Data Advisor. 


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