David Tougeron, MD, Poitiers University Hospital, shares his insights on results from the PRODIGE 59-DURIGAST trial, a randomized phase 2 trial comparing FOLFIRI plus durvalumab vs FOLFIRI plus durvalumab plus tremelimumab as a second-line treatment for patients with advanced gastric or gastroesophageal junction (GEJ) adenocarcinoma. While the study did not meet its primary end point of progression-free survival, the combination of FOLFIRI plus durvalumab plus tremelimumab may convey a benefit to certain subgroups of patients.

These results were first presented at the 2022 European Society for Medical Oncology (ESMO) Congress.

Transcript:

Dear colleagues, I am Dr. Tougeron, from France and I was happy to present at the 2022 ESMO Congress the result of the French academic trial, DURIGAST.

The DURIGAST trial is a coordinated Fédération Française de Cancérologie Digestive on metastatic gastric and gastroesophageal junction adenocarcinoma comparing FOLFIRI plus durvalumab versus FOLFIRI plus durvalumab and a tremelimumab in second-line setting.

The primary endpoint is progression-free survival at 4 months, and we expected that to be 70%. We have enrolled more than 100 patients in this trial, about 50 in each arm. First, we demonstrated good safety profile of both combinations, because grade 3/4 adverse events relative to the treatment have 47.8% in each arm. Concerning the primary endpoint, PFS at 4 months was 44% in the FOLFIRI-durvalumab arm, as compared 55.6% in FOLFIRI-durvalumab-tremelimumab arms. Then, the primary endpoint was not met.

Nevertheless, median progression-free survival is 3.8 months in the FOLFIRI-durvalumab arm, as compared to 5.4 months in the FOLFIRI-durvalumab-tremelimumab arm. Concerning overall survival, median overall survival is near 1 year in both arms. And we have also observed a prolonged disease response in more than 1 year, especially in the FOLFIRI-durvalumab-tremelimumab arm, which is approximately 15% of the patient.

In conclusion, the primary endpoint of the trial was not met. We did have a good result, however, in the terms of survival, both in progression-free survival and overall survival, which has never been reached before with chemotherapy alone. Now, we need to identify the sub-group of patients with a good response to this combination of FOLFIRI plus immune checkpoint inhibitors. Ancillary studies are ongoing, investigating PD-L1 over-expression, tumor mutational burden, and microbiota analysis.

Thank you for your attention.

Source:

Tougeron D, Dahan L, El Hajbi F, et al. 1204MO – PRODIGE 59-DURIGAST trial: A randomised phase II study evaluating FOLFIRI plus durvalumab and FOLFIRI plus durvalumab plus tremelimumab in second-line treatment of patients with advanced gastric or gastro-oesophageal junction adenocarcinoma. Presented at: ESMO Congress; September 9-13, 2022. Paris, France and virtual. Abstract 1204MO.