Phase 2 study of bevacizumab plus carboplatin/nab-paclitaxel followed by bevacizumab plus nab‐paclitaxel for non‐squamous non‐small cell lung cancer with malignant pleural effusion

• Published in: Investigational new drugs Vol. 39; no. 4; pp. 1106 - 1112
• Main Authors: Tamiya, Motohiro, Tamiya, Akihiro, Suzuki, Hidekazu, Taniguchi, Yoshihiko, Katayama, Kanako, Minomo, Shojiro, Nakao, Keiko, Takeuchi, Naoko, Matsuda, Yoshinobu, Naito, Yujiro, Shiroyama, Takayuki, Okamoto, Norio, Okishio, Kyoichi, Kumagai, Toru, Atagi, Shinji, Imamura, Fumio, Hirashima, Tomonori
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.08.2021; Springer Nature B.V
• Subjects: Aged; Albumins - administration & dosage; Anemia; Antineoplastic Combined Chemotherapy Protocols - administration & dosage; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Bevacizumab; Bevacizumab - administration & dosage; Carboplatin; Carboplatin - administration & dosage; Carcinoma, Non-Small-Cell Lung - drug therapy; Carcinoma, Non-Small-Cell Lung - pathology; Chemotherapy; Clinical trials; Disease control; Female; Growth factors; Humans; Lung cancer; Lung Neoplasms - drug therapy; Lung Neoplasms - pathology; Male; Medicine; Medicine & Public Health; Middle Aged; Monoclonal antibodies; Neutropenia; Non-small cell lung carcinoma; Oncology; Paclitaxel; Paclitaxel - administration & dosage; Pathogenesis; Patients; Pharmacology/Toxicology; Phase II Studies; Pleural effusion; Pleural Effusion, Malignant - drug therapy; Pleural Effusion, Malignant - pathology; Progression-Free Survival; Prospective Studies; Small cell lung carcinoma; Survival Rate; Targeted cancer therapy; Toxicity; Vascular endothelial growth factor; Nab‐paclitaxel; Non‐small cell lung cancer; Malignant pleural effusion; Bevacizumab
• ISSN: 0167-6997; 1573-0646
• DOI: 10.1007/s10637-021-01076-8

Summary Objectives Vascular endothelial growth factor plays an important role in the pathogenesis of malignant pleural effusion (MPE). We previously showed the efficacy of bevacizumab (Bev) plus carboplatin (CBDCA)/paclitaxel (PTX) in the treatment of non-small lung cell cancer (NSCLC) with MPE. However, the toxicities were a little severe, and the efficacy was not satisfied sufficiently. Therefore, we conducted a phase II study for NSCLC with MPE to evaluate the efficacy and safety of Bev plus CBDCA/nab-PTX, which is a new combination therapy.  Methods  Chemotherapy-naive non-squamous (SQ) NSCLC patients with MPE participated in the study. A single aspiration (not allowing chest tube drainage) was allowed before chemotherapy. Patients received a maximum of six cycles of Bev (15 mg/kg, day1) plus CBDCA (AUC 6, day1)/nab-PTX (100 mg/m 2 , day1, 8) every 3 weeks followed by Bev (15 mg/kg, day1) plus nab-PTX (100 mg/m 2 , day1, 8) every 3 weeks without disease progression or unacceptable severe toxicities. The primary endpoint was objective response rate (ORR).  Results  The study enrollment was ceased because of suspension of the registration period (as scheduled) after 12 of 20 planned patients were treated successfully between March 2014 and February 2018. The ORR was 58.3 % (95 % CI, 27.7–84.8 %), and the disease control rate was 100 % (95 % CI, 73.5–100 %). Eight patients received maintenance therapy. Median progression-free and overall survival times were 14.4 and 26.9 months, respectively. Most patients experienced hematological toxicities, including ≥ grade 3 neutropenia and anemia; none experienced severe bleeding events and grade 5 toxicities.  Conclusion  The combination of Bev plus CBDCA/nab-PTX, a novel combination, might have efficacy with acceptable toxicities in chemotherapy-naïve non-SQ NSCLC patients with MPE. Trial Registration University Hospital Medical Information Network in Japan (UMIN) Clinical Trials Registry (No. UMIN000013329) registered on 4th March 2014.