Worth the wait?

Top Line: Do patients with resectable or borderline resectable pancreatic cancer benefit from neoadjuvant chemoradiation?

The Study: Neoadjuvant therapy is often employed for borderline resectable pancreatic cancer, but when it comes to resectable pancreatic cancer (especially with no high risk features), the NCCN doesn’t recommend neoadjuvant therapy. Back at ASCO 2018, we were all pumped about the initial results of the PREOPANC trial, which showed improved survival (median 17.1 v 13.7 mo) with neoadjuvant chemoradiation compared to adjuvant gemcitabine-based chemo. But then the final publication in 2020 found no significant difference in OS (16 v 14.3 mo). So, now we have long-term results of PREOPANC. As a reminder, patients with resectable (~55%) and borderline resectable (~45%) pancreatic cancer were randomized to either 1) surgery followed by 6 cycles adjuvant gemcitabine or 2) 3 cycles of neoadjuvant gemcitabine with 2.4Gy x 15 = 36 Gy during the second cycle, surgery, and 4 cycles adjuvant gemcitabine. In the up-front surgery arm, 72% actually underwent resection compared to 61% in the neoadjuvant arm. The R0 resection rate was higher with neoadjuvant therapy (45% v 28%). With a median follow-up of 59 months (previously 27 months), neoadjuvant chemoradiation resulted in a significant improvement in median OS (15.7 v 14.3 mo). At 5 years, OS was higher with neoadjuvant therapy (20.5% v 6.5%). The difference seems to have come after 12-18 months when survival curves diverged–suggesting a benefit among patients who don’t experience early disease progression. Disease free survival, locoregional failure-free interval, and distant metastasis free survival were all better with neoadjuvant CRT. Survival outcomes favored neoadjuvant CRT in all subgroups including resectability status. However, the benefit was more pronounced for borderline resectable disease. Unfortunately, single-agent gemcitabine is no longer preferred, and PREOPANC-2 is comparing neoadjuvant CRT to FOLFIRINOX.

TBL: Long-term results of PREOPANC show improved overall survival with neoadjuvant chemoradiation and adjuvant gemcitabine compared to up-front surgery and adjuvant gemcitabine alone for resectable and borderline resectable pancreatic cancer. | Versteijne, J Clin Oncol 2022