Erlotinib and bevacizumab in elderly patients ≥75 years old with non-small cell lung cancer harboring epidermal growth factor receptor mutations

• Published in: Investigational new drugs Vol. 39; no. 1; pp. 210 - 216
• Main Authors: Aoshima, Yoichiro, Karayama, Masato, Inui, Naoki, Yasui, Hideki, Hozumi, Hironao, Suzuki, Yuzo, Furuhashi, Kazuki, Fujisawa, Tomoyuki, Enomoto, Noriyuki, Nakamura, Yutaro, Mikamo, Masashi, Matsuura, Shun, Kusagaya, Hideki, Kaida, Yusuke, Uto, Tomohiro, Hashimoto, Dai, Matsui, Takashi, Asada, Kazuhiro, Suda, Takafumi
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.02.2021; Springer Nature B.V
• Subjects: Adverse events; Aged; Aged, 80 and over; Antineoplastic Agents - administration & dosage; Antineoplastic Agents - adverse effects; Antineoplastic Agents - therapeutic use; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Bevacizumab; Bevacizumab - administration & dosage; Bevacizumab - adverse effects; Bevacizumab - therapeutic use; Carcinoma, Non-Small-Cell Lung - drug therapy; Carcinoma, Non-Small-Cell Lung - genetics; Confidence intervals; Disease control; Dose-Response Relationship, Drug; Epidermal growth factor; Epidermal growth factor receptors; ErbB Receptors - genetics; Erlotinib Hydrochloride - administration & dosage; Erlotinib Hydrochloride - adverse effects; Erlotinib Hydrochloride - therapeutic use; Female; Gene deletion; Growth factors; Humans; Immunotherapy; Inhibitor drugs; Lung cancer; Lung Neoplasms - drug therapy; Lung Neoplasms - genetics; Male; Medicine; Medicine & Public Health; Monoclonal antibodies; Mutation; Nausea; Non-small cell lung carcinoma; Older people; Oncology; Pharmacology/Toxicology; Phase II Studies; Pneumothorax; Proteinuria; Receptors; Small cell lung carcinoma; Survival; Targeted cancer therapy; Toxicity; Epidermal growth factor receptor mutation; Erlotinib; Targeted therapy; Elderly patients; Bevacizumab
• ISSN: 0167-6997; 1573-0646
• DOI: 10.1007/s10637-020-00988-1

Summary The efficacy and safety of combination therapy with erlotinib and bevacizumab in elderly patients with non-small-cell lung cancer (NSCLC) harboring epidermal growth factor receptor ( EGFR ) gene mutations are unknown. Elderly patients aged ≥75 years old with advanced or recurrent NSCLC and EGFR mutations (exon 19 deletion or L858R mutation in exon 21) received erlotinib (150 mg, daily) and bevacizumab (15 mg/kg on day 1 of a 21-day cycle) until disease progression or the occurrence of unacceptable toxicities. The primary endpoint was progression-free survival from enrollment. Twenty-five patients were enrolled in this study, and the median age was 80 years. Fifteen (60.0%) and 10 patients (40.0%) had exon 21 L858R mutations and exon 19 deletions, respectively. The median progression-free survival from enrollment was 12.6 months [95% confidence interval (CI): 8.0–33.7 months]. The objective response rate was 88.0% [95% CI: 74.0%–99.0%], and the disease control rate was 100% [95% CI: 88.7%–100%]. Grade 3 or higher adverse events occurred in 12 patients (48.0%), and rash and nausea were the most common. Grade 3 or higher bevacizumab-related toxicities occurred in 4 (16.0%) patients, including proteinuria ( n  = 2), gastrointestinal perforation ( n  = 1) and pneumothorax (n = 1). A dose reduction of erlotinib and cessation of bevacizumab was required in 16 (64.0%) and 18 patients (72.0%), respectively. Erlotinib and bevacizumab combination therapy showed a minimal survival benefit with frequent dose reductions and/or treatment discontinuations in elderly patients with EGFR -positive NSCLC.