Phase III study comparing bevacizumab plus erlotinib to erlotinib in patients with untreated NSCLC harboring activating EGFR mutations: NEJ026
Abstract
9006 Background: Development of treatment for EGFR-mutated non-small-cell lung cancer (NSCLC) had been focused on monotherapy of gefitinib, erlotinib, or afatinib. Combinations of EGFR-TKIs and VEGF inhibitors are one of candidates for next strategy for EGFR-mutated tumor. We conducted a phase III study comparing BE to E. Methods: Chemotherapy-naïve pts with advanced non-squamous NSCLC harbouring EGFR-mutation were randomly assigned to receive either combination with erlotinib (150 mg daily) plus bevacizumab (15 mg/kg iv q3w) or erlotinib (150 mg daily). Status of EGFR mutations in plasma samples were monitored routinely during the study treatment and a second-line treatment. The primary endpoint was PFS. Secondary endpoints were OS, RR, safety, and QoL. We hypothesized that hazard ratio of PFS was 0.63. It was estimated that 147 events would be needed for the study to have a power of 80% and a two-sided significance level of 5%. Accordingly, this study was planned to enroll 214 pts in total. Results: Between Jun 3, 2015, and Aug 31, 2016, 228 pts with EGFR mutations were enrolled. There were one cessation prior to the study treatment and one withdrawal of consent; the remaining 226 pts were assigned to BE (n = 112) and E (n = 114). The interim analysis preplanned was performed at 117 PFS events using full analysis set of 224 pts except for both an ineligible case and a case lost to follow-up in E. Pts were followed up for a median of 12.4 months. The interim analysis showed that the study met its primary endpoint. At data cutoff (Sept 21, 2017), median PFS was 16.9 months (95% CI 14.2-21.0) in BE and 13.3 months (11.1-15.3) in E (p = 0.0157) (HR 0.605, 95% CI 0.417-0.877). Though hemorrhage, proteinuria, and hypertension as toxicities significantly increased in BE compared to in E, there was no significant difference among other toxicities between BE and E. Five cases had low-grade pneumonitis in E but no pneumonitis in BE. There was no treatment-related death. Conclusions: In this study, BE as a combination of EGFR-TKIs and VEGF inhibitors achieved durable response and good tolerability. This regimen is considered as a new standard treatment in EGFR-mutated NSCLC. Clinical trial information: UMIN000017069.
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The erlotinib-bevacizumab combination as upfront therapy in EGFR-mutated NSCLCs is associated with substantial PFS benefit over erlotinib alone (16-16.3 vs 9.7-12.4 months).
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- Authors
- Furuya, N., Fukuhara, T., Saito, H., Watanabe, K., Sugawara, S., Iwasawa, S., Tsunezuka, Y., Yamaguchi, O., Okada, M., Yoshimori, K., Nakachi, I., Gemma, A., Azuma, K., Hagiwara, K., Nukiwa, T., Morita, S., Kobayashi, K., Maemondo, M., & North East Japan Study Group
- Affiliations
- St. Marianna University School of Medicine (JP)
- Miyagi Prefectural Hospital Organization (JP)
- Kanagawa Cancer Center (JP)
- Sendai Kousei Hospital (JP)
- Chiba University Hospital (JP)
- Ishikawa Prefectural Central Hospital (JP)
- Saitama International Medical Center (JP)
- Hiroshima University (JP)
- Fukujuji Hospital (JP)
- Saiseikai Utsunomiya hospital (JP)
- Nippon Medical School (JP)
- Kurume University (JP)
- Jichi Medical University (JP)
- Tohoku University (JP)
- Kyoto University (JP)
- Iwate Medical University (JP)
- ORCID
- Venue
- Journal of Clinical Oncology
- Published
- 2018-05-20
- Volume
- 36
- Issue
- 15_suppl
- Pages
- 9006-9006
- ISSN
- 0732-183X (ISSN-L)
- 1527-7755
- OpenAlex
- W2891454322
- Cited by
- 59
- References
- 0
- Citations by year
- 2022: 2 · 2021: 5 · 2020: 10 · 2019: 27 · 2018: 15
- Type
- conference abstract
- Language
- en
- Open access
- closed
- Locations
- Journal of Clinical Oncology (publishedVersion)
- Institutional Repositories DataBase (IRDB) (submittedVersion)
- Iwate Medical University Repository (Iwate Medical University) (submittedVersion)
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Treatments and Mutations
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Diagnosis and Treatment
- Health Sciences › Medicine › Oncology › HER2/EGFR in Cancer Research
- Keywords
- bevacizumab, erlotinib, EGFR-mutant non-small cell lung cancer, EGFR tyrosine kinase inhibitors, VEGF inhibitors, combination therapy, progression-free survival, plasma biomarkers, quality of life, second-line therapy, gefitinib, afatinib, EGFR tyrosine kinase inhibitor resistance
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