Patient-Reported Outcomes (PROs) in NRG Oncology/RTOG 0436: A Phase 3 Trial Evaluating the Addition of Cetuximab to Paclitaxel, Cisplatin, and Radiation for Esophageal Cancer Treated Without Surgery International Journal of Radiation Oncology, Biology, Physics ORAL SCIENTIFIC SESSION| VOLUME 96, ISSUE 2, SUPPLEMENT , S31, OCTOBER 01, 2016
Date
10/01/2016Abstract
Purpose/Objective(s)
RTOG 0436 evaluated the benefit of cetuximab added to chemoradiation (CRT) for the non-operative management of esophageal cancer. The primary PRO objective was an improvement in the FACT-Esophageal cancer subscale (ECS) score with cetuximab. An important secondary objective was to assess if an improvement in ECS score is associated with a clinical complete response (cCR).
Materials/Methods
Patients (pts) with esophageal squamous cell or adenocarcinoma (T1N1M0; T2-4AnyNM0; AnyT/NM1a) were stratified by histology, tumor size, and celiac node status and randomized to weekly cisplatin (50 mg/m2), paclitaxel (25 mg /m2), and RT 50.4 Gy/1.8 Gy ± weekly cetuximab (400 mg/m2 day 1 then weekly 250 mg/m2). Overall survival (OS) was the primary endpoint, with a target accrual of 420 pts, providing at least 82% power to detect a 15-20% ECS improvement on the cetuximab arm; α = 0.05. The ECS, version 4, was given at baseline, 6-8 weeks (wks) post-treatment (tx), and at 1 and 2 years (yrs). An improvement in ECS, and its Swallowing Index (SI) and Eating Index (EI), was defined as increases of 5, 4, and 2 points, respectively, from baseline to 6-8 wks post-tx. Categorical data comparisons were performed using the chi-square test, and univariate logistic regression models were used to determine if cCR is associated with an improvement in ECS, SI, and EI scores.
Results
From 2008-2013, 344 pts were accrued, closing early after a protocol-specified analysis of OS did not meet continuing criteria. The ECS was completed by 261 pts (93%) at baseline, 173 (62%) 6-8 wks post-tx, 117 (42%) at 1 yr and 68 (25%) at 2 yrs. Pts completing the ECS were significantly associated with higher Zubrod (P = 0.01) and adenocarcinoma histology (P = 0.01). At 6-8 wks, pts on the CRT + cetuximab arm did not experience improved ECS scores (36.8 vs. 52.8 CRT; P = 0.96). Interestingly, pts with improved ECS were only 0.64 times as likely to be a cCR (95% CI: 0.34, 1.20); conversely, stable/declined ECS were 1.56 times (95% CI: 0.83, 2.94). The proportion of CRT pts with an improvement in SI at 6-8 wks was 9% higher than with cetuximab, but not significant (39.3% vs. 30.3%, P = 0.22). There was no association between tx arm and EI at 6-8 wks, or with ECS, SI or EI at 1 or 2 yrs. Pts with a cCR did have higher ECS, SI, and EI baseline scores, which may have partly contributed to these results. As previously reported, cCR, local control, and OS were not significantly different among treatment arms.
Conclusion
The addition of cetuximab to chemoradiation for the nonoperative management of esophageal cancer did not improve PROs, and unexpectedly, stable or declining ECS scores following therapy were associated with a cCR.
Author List
L.A. Kachnic J. Moughan M. Suntharalingam D.H. Ilson A.A. Konski W. Burrows C. Anker V. Bar Ad H.V. Thakrar J.P. Hayes E.M. Gore V.S. Kavadi R.U. Komaki A. Raben J.K. Giguere J. Pollock J.S. Greenberger G.M. Videtic K.S. Roof D. Watkins BrunerAuthor
Elizabeth M. Gore MD Professor in the Radiation Oncology department at Medical College of WisconsinView Online
