Radiation Therapy Does Not Improve Survival in Gastric/GEJ Cancers

CancerNetwork® spoke with Yelena Y. Janjigian, MD, chief attending physician of the Gastrointestinal Medical Oncology Service at Memorial Sloan Kettering Cancer Center, about developments in gastric or gastroesophageal junction (GEJ) cancers that she believes has the potential to change clinical practice.

Highlighting results from 2 clinical trials—the phase 3 TOPGEAR (NCT01924819) and the phase 3 ESOPEC (NCT02509286) trials—Janjigian stated that radiation therapy in patients with gastric and GEJ cancers will not improve survival in this population.^1,2

Furthermore, she expressed that for immunotherapy in the perioperative setting, the fluorouracil, leucovorin, oxaliplatin, and docetaxel (FLOT) regimen was the optimal therapy. She added that in the event that FLOT was unable, dose reductions or the removal of docetaxel were viable treatment strategies. Furthermore, she advised against the use of another combination, known as the CROSS regimen, which is composed of paclitaxel plus carboplatin (CarboTaxol) plus radiation, in patients with gastric or GEJ cancers.

Janjigian explained that patients should not be rushed to undergo radiation therapy if they are unable to receive an R0 resection, instead suggesting prolonged systemic therapy with either a triplet or a doublet regimen with immunotherapy. Only after the disease biology declares itself should one consider performing surgery. She concluded by emphasizing that FLOT with durvalumab (Imfinzi) is the optimal regimen to treat this systemic disease in the perioperative setting.

Transcript:

Other developments in gastric and esophageal cancer that are critical to recognize are that we have now had 2 randomized studies published in the New England Journal of Medicine, just in the past year: the phase 3 TOPGEAR study and the phase 3 ESOPEC study showing that radiation does not improve survival in these patients. Radiating the gastroesophageal junction or stomach will not help your patients live longer.

The critical piece to [remember] is that you cannot radiate with FLOT, and if you are going to use immunotherapy in the perioperative setting, FLOT is the best option. If the patient is not able to get FLOT, if you want to dose reduce once you get started or drop docetaxel, that’s okay. One important factor to [remember] is that for adenocarcinoma, the CROSS regimen, or [paclitaxel plus carboplatin (CarboTaxol)] plus radiation, should never be used. I have not used this regimen in over 6 years. That [is an] important development: that radiation does not improve survival.

If the patient is not able to get a complete resection or R0 resection––sometimes oncologists say, “we radiated because the R0 section was not possible.” That’s not the patient that you should be rushing to the [operating room] with; radiation will not help this patient live longer. You need to prolong systemic therapy, perhaps starting with either a triplet with immunotherapy or a doublet with immunotherapy. Only once the disease biology declares itself you could consider doing surgery.

The reason why the R0 resection rates are [higher] with radiation but do not translate to survival benefit is because this disease is systemic in nature. If you do not recognize that you are doing your patients a disservice and are ignoring the big factor that in patients who [receive radiation], R0 resection does not translate to survival benefit, that is the critical point. We need to treat systemic disease, and in the perioperative setting, FLOT plus durvalumab offers that important option.

References

1. Leong T, Smithers BM, Michael M, et al. Preoperative Chemoradiotherapy for Resectable Gastric Cancer. N Engl J Med. 2024;391(19):1810-1821. doi:10.1056/NEJMoa2405195
2. Hoeppner J, Brunner T, Schmoor C, et al. Perioperative chemotherapy or preoperative chemoradiotherapy in esophageal cancer. N Engl J Med. 2025;392(4):323-335. doi:10.1056/NEJMoa2409408