Clinical features and risk factors of panitumumab-induced interstitial lung disease: a postmarketing all-case surveillance study

• Published in: International journal of clinical oncology Vol. 20; no. 6; pp. 1063 - 1071
• Main Authors: Osawa, Masahiro, Kudoh, Shoji, Sakai, Fumikazu, Endo, Masahiro, Hamaguchi, Tetsuya, Ogino, Yumiko, Yoneoka, Miyo, Sakaguchi, Motonobu, Nishimoto, Hiroyuki, Gemma, Akihiko
• Format: Journal Article
• Language: English
• Published: Tokyo Springer Japan 01.12.2015; Springer Nature B.V
• Subjects: Adolescent; Adult; Age Factors; Aged; Aged, 80 and over; Antibodies, Monoclonal - adverse effects; Antineoplastic Agents - adverse effects; Cancer Research; Colorectal cancer; Colorectal Neoplasms - drug therapy; Female; Health Status; Humans; Incidence; Japan - epidemiology; Lung diseases; Lung Diseases, Interstitial - chemically induced; Lung Diseases, Interstitial - diagnostic imaging; Lung Diseases, Interstitial - epidemiology; Male; Medicine; Medicine & Public Health; Middle Aged; Neoplasm Recurrence, Local - drug therapy; Oncology; Original; Original Article; Product Surveillance, Postmarketing; Proportional Hazards Models; Receptor, Epidermal Growth Factor - antagonists & inhibitors; Receptor, Epidermal Growth Factor - metabolism; Risk Factors; Sex Factors; Studies; Surgical Oncology; Tomography, X-Ray Computed; Young Adult; Postmarketing surveillance; Interstitial lung disease; Panitumumab; Risk factors; Colorectal cancer
• ISSN: 1341-9625; 1437-7772
• DOI: 10.1007/s10147-015-0834-3

Background Drug-induced interstitial lung disease (ILD) is one of the most serious adverse reactions associated with the molecularly targeted drugs. Panitumumab has been approved for advanced or recurrent colorectal cancer. Although there were no adverse reaction reports of ILD in panitumumab monotherapy, 4 cases in combination chemotherapy were reported prior to its approval in Japan in 2010. Several studies also reported that the incidence of drug-induced ILD was higher in Japan than in other countries. The clinical features of ILD and the associated risk factors therefore need investigation. Methods We analyzed the data from 3085 unresectable, advanced or recurrent colorectal cancer patients enrolled in a postmarketing all-case surveillance study of panitumumab in Japan. ILD case reports were assessed based on the clinical and radiologic findings by a committee of external experts. Multivariate analysis using Cox’s hazard model identified the risk factors. Results ILD incidence (1.3 %) and mortality rates (51.3 %) were similar to those of patients receiving another anti-epidermal growth factor receptor (EGFR) monoclonal antibody in Japan. No specific onset timing was determined. Although panitumumab-specific ILD findings were not observed in computed tomography images or clinical practice, panitumumab can induce ILD with diffuse alveolar damage, as do the other anti-EGFR targeting drugs. A history/complication of ILD, male sex, poor general condition, and 65 years or older were identified as ILD risk factors, and no history of previous drug treatment was an apparent risk factor. Conclusion Panitumumab-induced ILD can occur at any time after initiation, and close and regular monitoring is needed.