NRG Oncology/RTOG 0848: Results after adjuvant chemotherapy +/- chemoradiation for patients with resected periampullary pancreatic adenocarcinoma (PA).

person Ross A. Abrams Rush University Medical Center, Chicago, IL info_outline Ross A. Abrams, Kathryn A. Winter, Karyn A. Goodman, William Regine, Howard Safran, Adam C. Berger, Chandan Guha, Lisa A. Kachnic, Michael Gillin, Samantha A. Seaward, Abraham Jing-Ching Wu, Jennifer J. Wu, Raid Aljumaily, Thomas A. DiPetrillo, Ravit Geva, Pramila R. Anne, Jennifer Yannucci, Darla K. Liles, Jennifer Moughan, Christopher H. Crane

Authors person Ross A. Abrams Rush University Medical Center, Chicago, IL info_outline Ross A. Abrams, Kathryn A. Winter, Karyn A. Goodman, William Regine, Howard Safran, Adam C. Berger, Chandan Guha, Lisa A. Kachnic, Michael Gillin, Samantha A. Seaward, Abraham Jing-Ching Wu, Jennifer J. Wu, Raid Aljumaily, Thomas A. DiPetrillo, Ravit Geva, Pramila R. Anne, Jennifer Yannucci, Darla K. Liles, Jennifer Moughan, Christopher H. Crane Organizations Rush University Medical Center, Chicago, IL, NRG Oncology SDMC/ACR, Philadelphia, PA, Mount Sinai, New York, NY, University of Maryland, Baltimore, MD, Brown University School of Medicine-Rhode Island Hospital, Providence, RI, Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, Montefiore Einstein Comprehensive Cancer Center, Bronx, NY, NewYork-Presbyterian/Columbia University Irving Medical Center, New York, NY, The University of Texas MD Anderson Cancer Center, Houston, TX, Kaiser Permanente, Oakland, CA, Memorial Sloan Kettering Cancer Center, New York, NY, Perlmutter Cancer Center, NYU Langone Health, New York, NY, University of Oklahoma Health Sciences Center, Oklahoma City, OK, Rhode Island Hospital, Providence, RI, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel, Jefferson Kimmel Cancer Center, Philadelphia, PA, Low Country Cancer Care Associates, Savannah, GA, East Carolina University Brody School of Medicine, Greenville, NC, NRG Oncology/SDMC/ACR, Philidelphia, PA Abstract Disclosures Research Funding No funding sources reported Background: If 5FU/Capecitabine sensitized radiotherapy (RT) is beneficial in the adjuvant (adj) management of PA after adj chemotherapy (chemo) is controversial. NRG/RTOG 0848 was designed to address this issue. Methods: This was a 2 step NCTN randomized (rndmzd) trial. Step 1 rndmzd patients (pts) to 5 cycles of gemcitabine +/- Erlotinib. Step 2 rndmzd pts to a 6th cycle of the same chemo +/- 5FU/Capecitabine with 50.4 Gy in 28 fractions RT (chemo+CRT). Step 1 eligibility included: R0/R1 resection, M0, ECOG PS 0-1, CA19-9≤180. Step 2 eligibility included > 4 cycles chemo (gem, gem combo, (m)FOLFIRINOX). RT included real time 3D/IMRT treatment (RX) plan review, scoring, and approval. At Step 2, pts stratified by nodal status (+ vs -), CA19-9 (≤90 vs > 90-180), surgical margins (R0 vs R1), and adjuvant chemo. Primary endpoint was OS. Secondary endpoints are DFS and AEs (CTCAEv4). Assuming 17 months median OS (chemo) and hypothesized 22.5 months (chemo+CRT), sample size was 354 pts (HR = 0.76, 80% power, 1-sided α = 0.05, 316 OS events). Due to lower than projected event rate, trial was amended to report at the earlier of (a) 316 observed OS events or (b) 5 years of follow-up time from Step 2 accrual closure (265 OS events, 72% power, same α). OS and DFS were estimated by Kaplan-Meier and arms compared using log-rank test. Multivariable analyses (MVA) used Cox proportional hazards models. Results: Accrual began 11/2009; closed 10/2018. 354 pts rndmzd (174 chemo, 180 chemo+CRT). Median follow-up for all & alive pts = 2 & 7 years, respectively, with 270 OS events. Median age 63, 45% female, 81% white, 13% AA. 83% R0, 26% node negative, 96% CA19-9 < 90. 13% of chemo+CRT pts did not receive RT. AEs were comparable (grade 4: 10% [chemo] vs 11% [chemo+CRT] and 1 grade 5 AE in each arm). Univariate OS/DFS results shown in Table. In initial MVA, RX, CA19-9, surgical margins were not statistically significantly associated with OS or DFS, but nodal status (OS, DFS) and race (OS) were. In further analyses, significant interactions were found between RX and nodal status for both OS and DFS. Node negative pts treated with chemo+CRT had better outcome than chemo pts; node positive pts did not (Table). Conclusions: Chemo+CRT did not improve OS overall, but did improve DFS. Both OS and DFS were improved with Chemo+CRT in node negative pts. Chemo+CRT did not increase Gr 4 or 5 AEs compared to chemo. Clinical trial information: NCT01013649. Univar (90% CI) OS – Chemo OS - Chemo+CRT DFS - Chemo DFS - Chemo+CRT MST, months 31 (25-38) 27 (25-32) 12 (9, 18) 16 (12, 20) 2yr% All 59 (52, 65) 58 (52, 64) 31 (26, 37) 36 (30, 42) 2yr% Node(-) 71 (60, 83) 76 (65, 86) 45 (33, 58) 56 (44, 68) 5yr% All 23 (18, 29) 28 (22, 34) 15 (11, 20) 21 (16, 27) 5yr% Node(-) 29 (17, 40) 48 (36, 61) 19 (9, 29) 47 (35, 59) HR Ref 0.96 (0.79, 1.18) Ref 0.82 (0.68, 0.99) 1-sided log-rank p-value 0.38 0.045 MVA: RX*Nodes Interaction HR(95%CI) 2.34 (1.27, 4.29) 2.05 (1.16, 3.61) p-value 0.0063 0.014