At the 2023 ASCO Gastrointestinal Cancers Symposium, Rachna Shroff, MD, University of Arizona Cancer Center, Tucson, AZ, discusses results from the phase 3 SWOG 1815 trial, comparing the addition of nab-paclitaxel to gemcitabine and cisplatin with gemcitabine and cisplatin for patients with newly diagnosed, advanced biliary tract cancers.

Dr Shroff explained that there was not a statistically significant improvement in the median overall survival with nab-paclitaxel to gemcitabine and cisplatin vs gemcitabine and cisplatin. However, she noted that this regimen may present a benefit for patients with locally advanced disease and gallbladder adenocarcinoma.

Transcript:

My name is Dr. Rachna Shroff. I am the chief of GI Medical Oncology at the University of Arizona Cancer Center. At the recent ASCO GI 2023, I had the privilege and opportunity to present the results of SWOG 1815, the first randomized phase 3 trial in advanced biliary tract cancers in the United States. This study was based on a phase 2 study that was done previously that involved 60 patients. It was a single arm study done at MD Anderson Cancer Center and Mayo Clinic—Arizona that looked at gemcitabine-cisplatin [gem-cis] and nab-paclitaxel as a triplet chemotherapy regimen in patients with newly diagnosed advanced biliary tract cancers. We know that gemcitabine-based regimens are the standard of care, and most recently, gemcitabine-cisplatin and durvalumab has been the new frontline therapy, but even then, the median overall survival is right around 1 year. The triplet regimen had some early signs of promising efficacy with the median overall survival of 19.2 months in the single arm phase 2 trial.

But we really needed to know how the triplet held up against the standard of care at the time of gemcitabine and cisplatin. SWOG 1815 was the pivotal, randomized phase 3 trial that looked at newly diagnosed biliary tract cancer patients and randomized them in a 2-to-1 fashion to receive gemcitabine, cisplatin, and nab-paclitaxel versus gemcitabine and cisplatin alone in a day 1 and 8 out of a 21-day cycle type of schedule. The doses for the triplet were really based on the phase 2 data, and patients were re-staged every 3 cycles and continued on therapy until progression or intolerance. The patients also had archival tissue banked as well as prospective blood banked, and there was a planned total of 441 patients with the primary endpoint of median overall survival, and a target hazard ratio of 0.7. There were some pre-specified stratification factors including performance status, disease site, and disease stage.

This study accrued incredibly rapidly. It opened to accrual in February of 2019 and closed to accrual with 441 patients accrued in February of 2021. It was a true testament to how quickly we can accrue in an NCTN mechanism. The results demonstrated that the median overall survival of gemcitabine-cisplatin plus nab-paclitaxel was numerically improved at 14 months compared to 12.7 months with gemcitabine and cisplatin alone. But this did not reach statistical significance. Similarly, the median progression-free survival was also slightly improved with the triplet and the overall response rate of gemcitabine-cisplatin plus nab-paclitaxel was 31% versus 22% in gem-cis alone.

The pre-specified stratification factors led to some exploratory analysis, specifically with some possibly interesting signals in disease site when we looked at gallbladder cancer where the median OS was improved and the overall response rate was 44% versus 22% in the gemcitabine-cisplatin arm. Similarly, when we looked at disease stage, locally advanced patients seemed to possibly benefit slightly more from the gemcitabine-cisplatin plus nab-paclitaxel with improvements in median overall survival. But I think it's important to point out that the numbers were really small in these subgroups, and so further exploratory studies would need to really understand this a little bit better.

When we look at toxicity, there were significantly more grade 3 to 5 hematologic toxicities, anemia, neutropenia, and thrombocytopenia in the gemcitabine-cispltin plus nab-paclitaxel arm compared to gemcitabine and cisplatin alone. Although, the treatment discontinuation rate between the 2 arms did not vary significantly.

Overall, when we look at this data, we really know that the primary endpoint of the study was not met with gemcitabine-cisplatin plus nab-paclitaxel not dramatically improving median overall survival compared to gemcitabine-cisplatin, but that there are some potential exploratory analyses that can be pursued in gallbladder cancer in locally advanced patients. And there are ongoing biomarker analyses that can hopefully help us look at molecular subsets to better determine if there are other patients that may benefit from the triplet regimen.

Source:

Shroff RT, Guthrie KA, Scott AJ, et al. SWOG 1815: A phase III trial of gemcitabine, cisplatin, and nab-paclitaxel versus gemcitabine and cisplatin in newly diagnosed, advanced biliary tract cancers. Presented at 2023 ASCO Gastrointestinal Symposium; January 19 – 21, 2023; San Francisco, California. Abstract LBA490