Navigating PD-L1–Low Gastroesophageal Cancer Treatment and Payer Challenges

In an interview with CancerNetwork®, Rutika Mehta, MD, MPH, director of Upper Gastrointestinal (GI) Medical Oncology at NYU Langone Health’s Perlmutter Cancer Center, discussed how she approaches treatment selection and insurance coverage for patients with PD-L1–low or –negative gastroesophageal cancer.

In the locally advanced setting, Mehta continues to offer perioperative durvalumab (Imfinzi) plus FLOT (fluorouracil, leucovorin, oxaliplatin, and docetaxel) to patients with a tumor area positivity (TAP) score below 1%, noting that this subgroup was small in the phase 3 MATTERHORN trial (NCT04592913) and that the FDA approval does not restrict use by PD-L1 status. In the metastatic setting, she outlined how HER2 status, claudin 18.2 expression, and combined positive score guide her choice among zanidatamab-hrii (Ziihera) with or without tislelizumab-jsgr (Tevimbra), claudin-directed therapy, and checkpoint inhibition.

Transcript:

Mehta: In the locally advanced setting, when I am deciding what to give my patients, especially if they have a tumor area positivity (TAP) score of less than 1%, I still would offer them D-FLOT, which is FLOT plus durvalumab. Again, go back to the original study, where less than 10% of patients had a TAP score of less than 1%. It’s a small subpopulation of patients, and therefore any data that we have been able to see from the MATTERHORN study cannot be broadly applied, since it’s a curative-intent setting and the hazard ratio did not significantly cross over 1.¹ I tend to prefer D-FLOT even in the TAP-negative patients. Based on the FDA approval, that’s reasonable. If there is a payer that’s giving me a hard time with approval of durvalumab in combination with FLOT, then I try to get an appeal and reiterate the FDA approval.

In the metastatic setting, it can be quite tricky. Now we have new treatment paradigms. In the HER2-positive setting, it doesn’t matter what your PD-L1 status is. There is now approval of chemotherapy plus zanidatamab with or without tislelizumab, so in the HER2-positive setting, it’s less of a concern.² In the claudin-positive patients, if they’re extremely positive, then I prefer a claudin-directed treatment. The patients who remain are the HER2-negative and claudin-negative patients. My threshold has been a combined positive score (CPS) of 5 for giving them immunotherapy. If I feel like there is a low burden of disease and the patient would probably do well over an extended period of time, I will prioritize giving them a checkpoint inhibitor as long as their CPS is 1 or more.

References

1. Janjigian YY, Al-Batran SE, Wainberg ZA, et al. Perioperative durvalumab in gastric and gastroesophageal junction cancer. N Engl J Med. 2025;393(3):217-230. doi:10.1056/NEJMoa2503701

2. Elimova E, Rha SY, Shitara K, et al. Zanidatamab + chemotherapy (CT) ± tislelizumab for first-line (1L) HER2-positive (HER2+) locally advanced, unresectable, or metastatic gastroesophageal adenocarcinoma (mGEA): primary analysis from HERIZON-GEA-01. J Clin Oncol. 2026;44(suppl 2):LBA285. doi:10.1200/JCO.2026.44.2_suppl.LBA285