Phase II Study of Immunotherapy With Tecemotide and Bevacizumab After Chemoradiation in Patients With Unresectable Stage III Non-Squamous Non–Small-Cell Lung Cancer (NS-NSCLC): A Trial of the ECOG-ACRIN Cancer Research Group (E6508)

Jyoti D. Patel, Ju Whei Lee, David P. Carbone, Henry Wagner, Anil Shanker, Maria Teresa P. de Aquino, Leora Horn, Melissa L. Johnson, David E. Gerber, Jane Jijun Liu, Millie S. Das, Mohammed Ali Al-Nsour, Christopher S.R. Dakhil, Suresh Ramalingam, Joan H. Schiller

Research output: Contribution to journalArticle

Abstract

Introduction: Although chemoradiotherapy (CRT) is the standard of care for patients with unresectable stage III non–small-cell lung cancer (LA-NSCLC), most patients relapse. Tecemotide is a MUC1 antigen-specific cancer immunotherapy vaccine. Bevacizumab improves survival in advanced nonsquamous (NS)-NSCLC and has a role in immune modulation. This phase II trial tested the combination of tecemotide and bevacizumab following CRT in patients with LA-NSCLC. Patients and Methods: Subjects with stage III NS-NSCLC suitable for CRT received carboplatin/paclitaxel weekly + 66 Gy followed by 2 cycles of consolidation carboplatin/paclitaxel ≤ 4 weeks of completion of CRT (Step 1). Patients with partial response/stable disease after consolidation therapy were registered onto step 2, which was 6 weekly tecemotide injections followed by every 6 weekly injections and bevacizumab every 3 weeks for up to 34 doses. The primary endpoint was to determine the safety of this regimen. Results: Seventy patients were enrolled; 68 patients (median age, 63 years; 56% male; 57% stage IIIA) initiated therapy, but only 39 patients completed CRT and consolidation therapy per protocol, primarily owing to disease progression or toxicity. Thirty-three patients (median age, 61 years; 58% male; 61% stage IIIA) were registered to step 2 (tecemotide + bevacizumab). The median number of step 2 cycles received was 11 (range, 2-25). Step 2 worst toxicity included grade 3, N = 9; grade 4, N = 1; and grade 5, N = 1. Grade 5 toxicity in step 2 was esophageal perforation attributed to bevacizumab. Among the treated and eligible patients (n = 32) who were treated on step 2, the median overall survival was 42.7 months (95% confidence interval, 21.7-63.3 months), and the median progression-free survival was 14.9 months (95% confidence interval, 11.0-20.9 months) from step 1 registration. Conclusions: This cooperative group trial met its endpoint, demonstrating tolerability of bevacizumab + tecemotide after CRT and consolidation. In this selected group of patients, the median progression-free survival and overall survival are encouraging. Given that consolidation immunotherapy is now a standard of care following CRT in patients with LA-NSCLC, these results support a role for continued investigation of antiangiogenic and immunotherapy combinations in LA-NSCLC.

Original languageEnglish (US)
JournalClinical Lung Cancer
DOIs
StateAccepted/In press - 2020

All Science Journal Classification (ASJC) codes

  • Oncology
  • Pulmonary and Respiratory Medicine
  • Cancer Research

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    Patel, J. D., Lee, J. W., Carbone, D. P., Wagner, H., Shanker, A., de Aquino, M. T. P., Horn, L., Johnson, M. L., Gerber, D. E., Liu, J. J., Das, M. S., Al-Nsour, M. A., Dakhil, C. S. R., Ramalingam, S., & Schiller, J. H. (Accepted/In press). Phase II Study of Immunotherapy With Tecemotide and Bevacizumab After Chemoradiation in Patients With Unresectable Stage III Non-Squamous Non–Small-Cell Lung Cancer (NS-NSCLC): A Trial of the ECOG-ACRIN Cancer Research Group (E6508). Clinical Lung Cancer. https://doi.org/10.1016/j.cllc.2020.06.007