PFS a potential surrogate marker for OS in advanced BTC trials

In advanced biliary tract cancer (BTC), progression-free survival (PFS) is moderately associated with overall survival (OS) both the trial- and patient-level analyses, while objective response rate (ORR) and disease control rate (DCR) show a low correlation.

The authors conducted a systematic review of PubMed, Embase, Cochrane, clinicaltrials.gov, and conference proceedings for phase II-III trials in advanced BTC for the trial-level analysis. They measured the association with OS with PFS, ORR, DCR using a weighted linear regression. For the patient-level analysis, the authors included five randomized trials and three real-world datasets to assess patients.

Forty-one studies, which involved 88 treatment arms and 7,817 patients, were included in the trial-level analysis. The coefficient of determination of the model was 0.71 (95 percent confidence interval [CI], 0.56‒0.86) for PFS, 0.01 (95 percent CI, 0‒0.08) for ORR, and 0.39 (95 percent CI, 0.14‒0.64) for DCR. These results persisted in predefined subgroup analysis.

The patient-level analysis included a total of 2,506 patients, 783 in randomized trials (first-line n=512, second-line n=271) and 1,723 in routine clinical care (first-line chemotherapy n=773, first-line chemotherapy-durvalumab n=628, second-line chemotherapy n=322).

The correlation coefficient across the distinct datasets ranged from 0.73 to 0.86 for PFS. No significant association was observed between response and survival in a responder analysis.

“While PFS is currently the best candidate surrogate marker for OS, our results highlight the need for novel endpoints in this field,” the authors said.

“Surrogate endpoints are increasingly used in BTC trials. While this may expedite drug approval and decrease costs, surrogate endpoints may not always correlate with an OS advantage,” they noted.