A phase II study of carboplatin, pemetrexed, and bevacizumab followed by erlotinib and bevacizumab maintenance for non-squamous non-small cell lung cancer with wild-type EGFR (HOT1101)

• Published in: International journal of clinical oncology 2018-12, Vol.23 (6), p.1060-1069
• Main Authors: Takashina, Taichi, Asahina, Hajime, Oizumi, Satoshi, Yamada, Noriyuki, Harada, Masao, Takamura, Kei, Yokouchi, Hiroshi, Harada, Toshiyuki, Honjo, Osamu, Ogi, Takahiro, Morikawa, Naoto, Kinoshita, Ichiro, Honda, Ryoichi, Nakano, Kosuke, Kanazawa, Kenya, Amano, Toraji, Dosaka-Akita, Hirotoshi, Isobe, Hiroshi, Nishimura, Masaharu
• Format: Article
• Language: English
• Subjects: Adenocarcinoma - drug therapy; Adenocarcinoma - genetics; Adenocarcinoma - pathology; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Bevacizumab; Bevacizumab - administration & dosage; Cancer Research; Carboplatin; Carboplatin - administration & dosage; Carcinoma, Non-Small-Cell Lung - drug therapy; Carcinoma, Non-Small-Cell Lung - genetics; Carcinoma, Non-Small-Cell Lung - pathology; Disease control; Epidermal growth factor receptors; ErbB Receptors - genetics; Erlotinib Hydrochloride - administration & dosage; Female; Humans; Immunotherapy; Induction therapy; Lung cancer; Lung Neoplasms - drug therapy; Lung Neoplasms - genetics; Lung Neoplasms - pathology; Male; Medicine; Medicine & Public Health; Middle Aged; Monoclonal antibodies; Mutation; Neutropenia; Non-small cell lung carcinoma; Oncology; Original Article; Patients; Pemetrexed - administration & dosage; Prognosis; Prospective Studies; Quality of Life; Surgical Oncology; Survival Rate; Targeted cancer therapy; Toxicity; Young Adult
• ISSN: 1341-9625; 1437-7772
• DOI: 10.1007/s10147-018-1318-z

Background This study evaluated the efficacy and safety of switch maintenance erlotinib and bevacizumab after induction therapy with carboplatin/pemetrexed/bevacizumab for non-squamous non-small cell lung cancer (NSCLC) with wild-type EGFR . Methods Enrolled patients had treatment-naïve, advanced non-squamous NSCLC with wild-type EGFR . Carboplatin [area under the curve (AUC) 5.0], pemetrexed (500 mg/m2) and bevacizumab (15 mg/kg) were administered on day 1 every 3 weeks for 4–6 cycles. Maintenance therapy with erlotinib (150 mg/body) on day 1 through 21 plus bevacizumab on day 1 every 3 weeks was continued until disease progression or unacceptable toxicity. The primary endpoint was 6-month progression-free survival (PFS); secondary endpoints included overall survival (OS), overall response rate (ORR), toxicity, and quality of life (QOL). Results Fifty-one patients were enrolled between September 2011 and June 2014. The median number of cycles for induction and maintenance therapy was 4 (range 1–6) and 4 (range 1–20). Twenty-nine patients (58%) received maintenance therapy. The 6-month PFS rate was 59.5% [95% confidence interval (CI) 45.0–72.6%]. The ORR was 48.0% (95% CI 34.8–61.5%), and disease control rate was 86.0% (95% CI 73.8–93.0%). The median PFS and OS were 6.5 months (95% CI 5.8–7.2 months) and 21.4 months (95% CI 15.9–26.9 months), respectively. Although grades ≥ 3 adverse events were observed in 33 patients (66.0%), most were hematologic; there was no febrile neutropenia. QOL was maintained throughout treatment. Conclusions Carboplatin/pemetrexed/bevacizumab followed by erlotinib and bevacizumab maintenance showed modest efficacy and was well tolerated in non-squamous NSCLC patients with wild-type EGFR . Trial registration UMIN000005872.