Outcomes After Combined Modality Therapy for EGFR-Mutant and Wild-Type Locally Advanced NSCLC

Author:

Mak Raymond H.1,Doran Elizabeth2,Muzikansky Alona3,Kang Josephine1,Neal Joel W.4,Choi Noah C.156,Willers Henning156,Jackman David M.26,Sequist Lecia V.176

Affiliation:

1. a Harvard Radiation Oncology Program, Boston, Massachusetts, USA;

2. b Lowe Center for Thoracic Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA;

3. c Biostatistics Center, Massachusetts General Hospital Cancer Center, Boston, Massachusetts, USA

4. f Stanford Cancer Center, Stanford, California, USA;

5. d Department of Radiation Oncology, Massachusetts General Hospital Cancer Center, Boston, Massachusetts, USA

6. h Harvard Medical School, Boston, Massachusetts, USA

7. e Center for Thoracic Cancers, Massachusetts General Hospital Cancer Center, Boston, Massachusetts, USA;

Abstract

Abstract Learning Objectives After completing this course, the reader will be able to: Describe locoregional recurrence rates in EGFR-mutant and wild-type EGFR patients in this study who had locally advanced non-small cell lung cancer that was treated with combined modality therapy, including thoracic radiation therapy.Compare the locoregional recurrence rate in EGFR-mutant and wild-type EGFR patients in this study who had locally advanced non-small cell lung cancer and who were treated without surgery. This article is available for continuing medical education credit at CME.TheOncologist.com Background. Epidermal growth factor receptor (EGFR) mutations identify a unique biological subtype of non-small cell lung cancer (NSCLC). Treatment outcomes for EGFR-mutant locally advanced NSCLC patients have not been well described. Methods. We retrospectively examined outcomes after combined modality therapy including thoracic radiation therapy (RT) in 123 patients with locally advanced NSCLC and known EGFR mutation status. Outcomes were compared using Kaplan–Meier analysis, the log-rank test, and multivariate Cox regression models. Results. All 123 patients underwent thoracic RT; 25% had tumors with EGFR mutations and 94% had stage III disease. Overall, 81% received chemotherapy concurrent with RT and 55% underwent surgical resection. With a median follow-up of 27.5 months, the overall survival (OS) rate was significantly higher in patients with EGFR-mutant tumors than in those with wild-type EGFR tumors (2-year estimate: 92.6% versus 69.0%; p = .04). The 2-year relapse-free survival and distant recurrence rates did not differ significantly by genotype. The 2-year locoregional recurrence rate (LRR) was significantly lower in EGFR-mutant than in wild-type EGFR patients (17.8% versus 41.7%; p = .005). EGFR-mutant genotype was associated with a lower risk for LRR on multivariate analysis, but not OS, after adjusting for surgery and other potential confounders. Conclusion. We observed that EGFR-mutant patients with locally advanced NSCLC treated with RT had lower rates of LRR than wild-type EGFR patients, raising the hypothesis that EGFR mutations may confer sensitivity to RT and/or chemotherapy. The association between mutation status and OS after combined modality therapy was less robust. Our data may serve as a useful baseline estimate of outcomes by EGFR genotype for future prospective studies.

Funder

National Cancer Institute

Dana-Farber/Harvard Cancer Center SPORE in Lung Cancer

Publisher

Oxford University Press (OUP)

Subject

Cancer Research,Oncology

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