Purpose Whether adding fluoropyrimidine sensitized radiotherapy (CXRT) to adjuvant chemotherapy improves overall survival after curative intent resection of the pancreatic head. Methods A multi-center, randomized phase III, 2 step trial. Step 1: gemcitabine vs. gemcitabine+erlotinib (previously reported). Step 2: randomization to 6 th chemo cycle +/-CXRT after 5 cycles of step 1 chemotherapy without progression. Outcomes of Step 2 randomization are reported here. Assuming 17 months median OS (chemotherapy alone), sample size was 354 patients (HR=0.76, 80% power, 1-sided α=0.05, 316 OS events). OS/DFS were estimated by Kaplan-Meier and arms compared using log-rank test. Results 354 patients (median age 63, 55% male, 56% PS 1) were randomized to chemotherapy(174) or chemotherapy+CXRT(180). Univariate median and 5-year OS (90% CIs) were 2.6 years (2.1-3.1) and 23.1% (17.7-28.6) for chemotherapy alone, and 2.3 years (2.0-2.6) and 27.9% (22.2-33.6) for chemotherapy+CXRT. The OS primary endpoint was not met (HR 0.96, 90% CI: 0.79–1.18, 1-sided p=0.38, 2-sided p=0.77). Chemotherapy+CXRT was associated with a trend for improved DFS (univariately) (HR 0.82, 95% CI: 0.65-1.03, p=0.089), without increase in grade 4/5 toxicities. However, grade 3 toxicity increased (38% vs. 19%, p<0.001). Significantly, treatment by nodal status interactions showed that CXRT improved OS (p=0.0063) and DFS (p=0.014) in node negative patients. Conclusion Overall, the addition of adjuvant CXRT to adjuvant gemcitabine did not statistically significantly improve OS, DFS, or increase grade 4/5 toxicity. For node negative patients, CXRT improved OS and DFS. These results, if confirmed in studies with current or future systemic therapies, would support the use of adjuvant/ neoadjuvant CXRT for node negative patients.
Abrams et al. (Tue,) studied this question.
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