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Purpose and Objectives This report presents the analysis of the RTOG 0537 multicenter randomized study that compared acupuncture-like transcutaneous stimulation (ALTENS) with pilocarpine (PC) for relieving radiation-induced xerostomia. Methods and Materials Eligible patients were randomized to twice-weekly 20-minute ALTENS sessions for 24 sessions during 12 weeks or PC (5 mg 3 times daily for 12 weeks). The primary endpoint was the change in the University of Michigan Xerostomia-Related Quality of Life Scale (XeQOLS) scores from baseline to 9 months from randomization (MFR). Secondary endpoints included basal and citric acid primed whole salivary production (WSP), ratios of positive responders (defined as patients with ≥20% reduction in overall radiation-induced xerostomia symptom burden), and the presence of adverse events based on the Common Terminology Criteria for Adverse Events version 3. An intention-to-treat analysis was conducted. Results One hundred forty-eight patients were randomized. Only 96 patients completed the required XeQOLS and were evaluable at 9 MFR (representing merely 68.6% statistical power). Seventy-six patients were evaluable at 15 MFR. The median change in the overall XeQOLS in ALTENS and PC groups at 9 and 15 MFR were −0.53 and −0.27 ( P =.45) and −0.6 and −0.47 ( P =.21). The corresponding percentages of positive responders were 81% and 72% ( P =.34) and 83% and 63% ( P =.04). Changes in WSP were not significantly different between the groups. Grade 3 or less adverse events, mostly consisting of grade 1, developed in 20.8% of patients in the ALTENS group and in 61.6% of the PC group. Conclusions The observed effect size was smaller than hypothesized, and statistical power was limited because only 96 of the recruited 148 patients were evaluable. The primary endpoint—the change in radiation-induced xerostomia symptom burden at 9 MFR—was not significantly different between the ALTENS and PC groups. There was significantly less toxicity in patients receiving ALTENS.

Importance The role of epidermal growth factor receptor (EGFR) inhibition in chemoradation strategies in the nonoperative treatment of patients with esophageal cancer remains uncertain. Objective To evaluate the benefit of cetuximab added to concurrent chemoradiation therapy for patients undergoing nonoperative treatment of esophageal carcinoma. Design, Setting, and Participants A National Cancer Institute (NCI) sponsored, multicenter, phase 3, randomized clinical trial open to patients with biopsy-proven carcinoma of the esophagus. The study accrued 344 patients from 2008 to 2013. Interventions Patients were randomized to weekly concurrent cisplatin (50 mg/m 2 ), paclitaxel (25 mg/m 2 ), and daily radiation of 50.4 Gy/1.8 Gy fractions with or without weekly cetuximab (400 mg/m 2 on day 1 then 250 mg/m 2 weekly). Main Outcomes and Measures Overall survival (OS) was the primary endpoint, with a study designed to detect an increase in 2-year OS from 41% to 53%; 80% power and 1-sided α = .025. Results Between June 30, 2008, and February 8, 2013, 344 patients were enrolled. This analysis used all data received at NRG Oncology through April 12, 2015. Sixteen patients were ineligible, resulting in 328 evaluable patients, 159 in the experimental arm and 169 in the control arm. Patients were well matched between the treatment arms for patient and tumor characteristics: 263 (80%) with T3 or T4 disease, 215 (66%) N1, and 62 (19%) with celiac nodal involvement. Incidence of grade 3, 4, or 5 treatment-related adverse events at any time was 71 (46%), 35 (23%), or 6 (4%) in the experimental arm and 83 (50%), 28 (17%), or 2 (1%) in the control arm, respectively. A clinical complete response (cCR) rate of 81 (56%) was observed in the experimental arm vs 92 (58%) in the control arm (Fisher exact test, P = .66). No differences were seen in cCR between treatment arms for either histology (adenocarcinoma or squamous cell). Median follow-up for all patients was 18.6 months. The 24- and 36-month local failure for the experimental arm was 47% (95% CI, 38%-57%) and 49% (95% CI, 40%-59%) vs 49% (95% CI, 41%-58%) and 49% (95% CI, 41%-58%) for the control arm (HR, 0.92; 95% CI, 0.66-1.28; P = .65). The 24- and 36-month OS rates for the experimental arm were 45% (95% CI, 37%-53%) and 34% (95% CI, 26%-41%) vs 44% (95% CI, 36%-51%) and 28% (95% CI, 21%-35%) for the control arm (HR, 0.90; 95% CI, 0.70-1.16; P = .47). Conclusions and Relevance The addition of cetuximab to concurrent chemoradiation did not improve OS. These phase 3 trial results point to little benefit to current EGFR-targeted agents in an unselected patient population, and highlight the need for predictive biomarkers in the treatment of esophageal cancer. Trial Registration clinicaltrials.gov Identifier:NCT00566852

4007 Background: RTOG 0436 is a randomized Ph III trial evaluating cetuximab added to concurrent chemoradiation for patients (pts) undergoing non-operative management of esophageal carcinoma (EC). ...

LBA6 Background: RTOG 0436 is a randomized Ph III trial designed to evaluate the benefit of cetuximab added to the concurrent chemoradiation for patients undergoing non-operative management of esophageal carcinoma. Methods: Pts with biopsy-proven squamous cell or adenocarcinoma of the esophagus (T1N1M0; T2-4 AnyN M0; Any T/N M1a) were randomized to weekly concurrent cisplatin (50 mg/m2), paclitaxel (25 mg/m2), and daily radiation 50.4 Gy/1.8 Gy fractions ± weekly cetuximab (400 mg/m2 day 1 then weekly 250 mg/m2). Patients were stratified by histology, tumor size (< 5 cm vs > 5cm), and the status of celiac lymph nodal involvement. Overall survival (OS) was the primary endpoint, with a planned accrual of 420 pts to detect an increase in 2-year OS from 41% to 53%; 80% power and 1-sided 0.025 alpha. An interim analysis of cCR was planned for the first 150 of each histology. Results: The study accrued 344 pts from 2008-2013 and 328 were eligible. Based on interim analyses, the study stopped accruing adeno pts in 5/2012 and SCC pts in 1/2013. Pts were well matched for pretreatment characteristics: 80% with T3/4 disease, 66% N1, and 19% with celiac nodal involvement. Incidence of grade 3/4/5 treatment (tx) related AEs was 45%, 22%, 4% in Arm 1 (cetuximab) and 49%, 17%, 1% in Arm 2 (no cetuximab). A cCR rate of 56% was observed in Arm 1 vs 59% in Arm 2 (p=0.72). No differences were seen in cCR between tx arms for either histology. The 12 and 24 mo OS rates for cCR pts were 79% and 58% vs 53% and 30% for those with residual disease (p