GI Upper
RTOG 0848 settles a long-debated question: adjuvant CXRT after pancreatic head resection adds toxicity without survival benefit over gemcitabine alone.
NRG Oncology/RTOG 0848 NCT01013649
ForResected pancreatic head adenocarcinoma, post adjuvant gemcitabine
TL;DROS HR 0.96 (90% CI 0.79-1.18), p=0.77; adding adjuvant chemoradiation to gemcitabine did not improve survival after resected pancreatic head adenoca.
vs leading data
- vs PRODIGE-24 (2018): gemcitabine backbone here predates the modern adjuvant FOLFIRINOX standard, limiting applicability
10 details 1 trial watching
Methods
- ๐ Phase III, 2-step design; Step 2 randomized 354 pts after curative pancreatic-head resection (median age 63, 56% PS 1)
- ๐ Backbone both arms: adjuvant gemcitabine (Step 1 tested gem vs gem+erlotinib)
- ๐ Experimental arm added a 6th cycle plus fluoropyrimidine-sensitized chemoradiation (CXRT)
CONSORT flow
Randomized 354
โ
Chemo alone
allocated 174
Chemo + CXRT
allocated 180
Results
- ๐ 1ยฐ EP OS not met: HR 0.96 (90% CI 0.79-1.18), 1-sided p=0.38, 2-sided p=0.77
- ๐ Univariate OS by arm (no significant difference)
Endpoint Chemo alone (n=174) Chemo+CXRT (n=180) Median OS 2.6 yr (90% CI 2.1-3.1) 2.3 yr (90% CI 2.0-2.6) 5-yr OS 23.1% (17.7-28.6) 27.9% (22.2-33.6) - ๐ DFS trend favored CXRT: HR 0.82 (95% CI 0.65-1.03), p=0.089
- ๐ Node-negative subgroup: significant treatment-by-nodal interaction for OS (p=0.0063) and DFS (p=0.014) favoring CXRT
Critique
- โ ๏ธ Grade 3 toxicity higher with CXRT: 38% vs 19% (p<0.001)
- โ ๏ธ No increase in grade 4/5 toxicity with CXRT
- โ ๏ธ Node-negative signal is subgroup-interaction only; hypothesis-generating, not practice-defining
Open questions
- Does adjuvant CXRT benefit node-negative pts with modern FOLFIRINOX backbone?
- Neoadjuvant chemoradiation role for node-negative resectable pancreatic cancer n=125 ยท primary completion 2027-06 ยท phase 2 neoadjuvant CRT arm in resectable/BR-PDAC
๐ Sources ยท ๐ 1 paper
Adjuvant Chemotherapy +/- Chemoradiotherapy for Adenocarcinoma of The Pancreatic Head: Results of The Radiotherapy Randomization of NRG Oncology/RTOG 0848
Abstract
Purpose: Whether adding fluoropyrimidine sensitized radiotherapy (CXRT) to adjuvant chemotherapy improves overall survival after curative intent resection of the pancreatic head.<br/><br/>Methods: A multi-center, randomized phase III, 2 step trial. Step 1: gemcitabine vs. gemcitabine+erlotinib (previously reported). Step 2: randomization to 6th chemo cycle +/-CXRT reported here. Assuming 17 months median OS (chemotherapy alone), sample size was 354 patients (HR=0.76, 80% power, 1-sided ฮฑ=0.05, 316 OS events). OS/DFS were estimated by Kaplan-Meier and arms compared using log-rank test.<br/><br/>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: 0.79โ1.18, 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.<br/><br/>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.