Clinical predictors of bevacizumab-associated intestinal perforation in non-small cell lung cancer

• Published in: Investigational new drugs Vol. 36; no. 4; pp. 696 - 701
• Main Authors: Tamiya, Motohiro, Suzuki, Hidekazu, Shiroyama, Takayuki, Tanaka, Ayako, Morishita, Naoko, Okamoto, Norio, Sakai, Kenichi, Shigeoka, Hironori, Kawahara, Kunimitsu, Hirashima, Tomonori
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.08.2018; Springer Nature B.V
• Subjects: Adult; Aged; Aged, 80 and over; Antineoplastic Agents, Immunological - adverse effects; Antineoplastic Agents, Immunological - therapeutic use; Bevacizumab; Bevacizumab - adverse effects; Bevacizumab - therapeutic use; Cancer; Carcinoma, Non-Small-Cell Lung - drug therapy; Chemotherapy; Colon; Complications; Confidence intervals; Cycle ratio; Demographics; Diarrhea; Disease-Free Survival; Female; Gastrointestinal diseases; Humans; Immunotherapy; Intestinal Perforation - chemically induced; Intestine; Lung cancer; Lung Neoplasms - drug therapy; Male; Medicine; Medicine & Public Health; Middle Aged; Monoclonal antibodies; Neoplasm Staging - methods; Neutropenia; Non-small cell lung carcinoma; Oncology; Patients; Perforation; Pharmacology/Toxicology; Phase III Studies; Retrospective Studies; Side effects; Stomatitis; Studies; Targeted cancer therapy; Ulcerative colitis; Prediction markers; NSCLC; Intestinal perforation; Bevacizumab
• ISSN: 0167-6997; 1573-0646
• DOI: 10.1007/s10637-018-0581-1

Summary Background Bevacizumab (Bev) is generally well-tolerated, and Bev-associated intestinal perforation (BAP) is a rare albeit serious side effect in cases of non-small cell lung cancer (NSCLC). Therefore, the present study aimed to identify clinical predictors of BAP to help predict and manage the development of life-threatening intestinal complications among patients receiving Bev. Methods This retrospective study evaluated demographic, clinical, and treatment factors for patients with NSCLC who were treated with Bev between February 2010 and August 2015 at our center. Results We identified 314 regimens (208 patients; median age: 65 years; 115 women) for analysis, which included 119 first-line regimens, 74 s-line regimens, and 121 third-line or later regimens. BAP occurred in 7 cases (2.23% among all regimens and 3.37% among all patients), which generally occurred during first- or second-line treatment and was caused by ulcerative colitis (1 case), colon diverticulitis (1 case), and idiopathic perforations (5 cases). Univariate analyses revealed that BAP was significantly associated with deteriorating PS during the first cycle of chemotherapy (odd ratio [OR]: 11.07, 95% confidence interval [CI]: 2.37–51.63, p  = 0.0022), grade ≥ 3 diarrhea (OR: 11.37, 95% CI: 2.37–54.50, p  = 0.0024), febrile neutropenia (OR: 9.16, 95% CI: 1.98–42.49, p  = 0.0047), and stomatitis (OR: 4.60, 95% CI: 1.01–21.04, p  = 0.0492). Conclusions Among patients with NSCLC, BAP was associated with deteriorating PS during the first cycle of chemotherapy, grade ≥ 3 diarrhea, febrile neutropenia, and stomatitis. Therefore, careful observation is needed for patients with NSCLC who receive Bev in any line of treatment, especially if they develop serious side effects that affect their PS or mucous membrane.