Dr. Harding on the Evolution of Frontline Chemotherapy Approaches in Advanced Biliary Tract Cancer

James Harding, MD, gastrointestinal oncologist, assistant attending physician, Memorial Sloan Kettering Cancer Center, discusses key trials contributing to the evolution of frontline chemoimmunotherapy approaches in advanced biliary tract cancer.

Systemic therapy with gemcitabine and cisplatin has traditionally been the only viable treatment option for unresectable biliary tract cancer that is not able to be treated with local therapy, Harding begins. However, two key trials aimed to expand the armamentarium in this disease space.

The large, global, phase 3 TOPAZ-1 study (NCT03875235) evaluated the addition of durvalumab (Imfinzi) to gemcitabine and cisplatin in patients with previously untreated, unresectable, or metastatic biliary tract cancer or those with recurrent disease after curative surgery or completion of adjuvant therapy, Harding says. Previously reported results showed that the combination significantly increased overall survival (OS) vs gemcitabine and cisplatin alone. Key secondary end points like overall response rate (ORR) and progression-free survival also favored the triplet combination.

Additional follow-up from TOPAZ-1 demonstrated a continued separation of the OS curves, he states. Moreover, a high percentage of the population remained alive at 24 months with the experimental regimen compared with those who received gemcitabine and cisplatin.

Subsequent subset analysis showed that the triplet regimen provided substantial benefit to all patients that were tested, Harding continues. Genetic analysis has also bolstered this conclusion by indicating that all genetic subsets would experience similar benefit from the triplet regimen. However, these ad hoc analyses were performed on a small sample size, Harding notes.

Overall, these data indicate that gemcitabine, cisplatin and durvalumab could become another standard of care in the frontline setting for advanced biliary tract cancer, he states.

In addition to gemcitabine, cisplatin and durvalumab, the development of other novel chemotherapy regimens has also been of great clinical interest, Harding continues. Notably, the addition of nab-paclitaxel (Abraxane) to gemcitabine and cisplatin was evaluated in the phase 3 SWOG 1815 intergroup study (NCT03768414). Results were recently reported and showed that triplet regimen did not result in statistically significant survival benefit vs gemcitabine and cisplatin alone. Although the study was ultimately negative, it proves that the clinical investigation of a rare disease subset is both viable and critical in the United States and Canada, Harding concludes.

Editor’s Note: Dr. Harding reports serving as a consultant or in an advisory role for Adaptimmune, Astrazeneca, Bristol Myers Squibb, Exelixis, Elevar, Eisai, Genoscience (uncompensated), Hepion, Imvax, Merck (DSMB) Medivir, QED, Tyra, Zymeworks (uncompensated); he reports receiving institutional research funding from Bristol Myers Squibb, Boehringer Ingelheim, CytomX, Debiopharm, Eli Lilly, Genoscience, Incyte, Loxo Oncology at Lilly, Novartis, Polaris, Pfizer, Zymeworks, Yiviva.