Randomized Phase II Study of Preoperative Chemoradiotherapy ± Panitumumab Followed by Consolidation Chemotherapy in Potentially Operable Locally Advanced (Stage IIIa, N2+) Non-Small Cell Lung Cancer: NRG Oncology RTOG 0839.

INTRODUCTION: Multimodality therapy has curative potential in locally advanced NSCLC. Mediastinal nodal sterilization (MNS) after induction chemoradiotherapy (CRT) can serve as an intermediate marker for efficacy. NRG Oncology Radiation Therapy Oncology Group (RTOG) 0229 demonstrated the feasibility and efficacy of combining full-dose radiation (61.2 Gy) with chemotherapy followed by resection and chemotherapy. On the basis of that experience and evidence that EGFR antibodies are radiosensitizing, we explored adding panitumumab to CRT followed by resection and consolidation chemotherapy in locally advanced NSCLC with a primary end point of MNS.
METHODS: Patients with resectable locally advanced NSCLC were eligible if deemed suitable for trimodality therapy before treatment. Surgeons were required to demonstrate expertise after CRT and adhere to specific management guidelines. Concurrent CRT consisted of weekly carboplatin (area under the curve = 2.0), paclitaxel (50 mg/m2), and 60 Gy of radiation therapy delivered in 30 fractions. There was a 2:1 randomization in favor of panitumumab at 2.5 mg/kg weekly for 6 weeks. The mediastinum was pathologically reassessed before or at the time of resection. Consolidation chemotherapy was weekly carboplatin (area under the curve = 6) and paclitaxel, 200 mg/m2 every 21 days for two courses. The study was designed to detect an improvement in MNS from 52% to 72%. With use of a 0.15 one-sided type 1 error and 80% power, 97 patients were needed.
RESULTS: The study was opened in November 2010 and closed in August 2015 by the Data Monitoring Committee after 71 patients had been accrued for futility and excessive toxicity in the experimental arm. A total of 60 patients were eligible: 19 patients (86%) who received CRT and 29 (76%) who received CRT plus panitumumab and underwent an operation. With regard to postoperative toxicity, there were three grade 4 adverse events (13.6%) and no grade 5 adverse events (0%) among those who received CRT versus six grade 4 (15.8%) and four grade 5 adverse events (10.5%) among those who received CRT plus panitumumab. The MNS rates were 68.2% (95% confidence interval: 45.1-86.1) and 50.0% (95% confidence interval: 33.4-66.6) for CRT and CRT plus panitumumab, respectively (p = 0.95).
CONCLUSION: The addition of panitumumab to CRT did not improve MNS. There was an unexpectedly high mortality rate in the panitumumab arm, although the relationship to panitumumab is unclear. The control arm had outcomes similar to those in NRG Oncology RTOG 0229.

RCT Entities:   Population Interventions Outcomes