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

Abstract

BackgroundDrug-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.MethodsWe 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.ResultsILD 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.ConclusionPanitumumab-induced ILD can occur at any time after initiation, and close and regular monitoring is needed.

The role of epidermal growth factor receptor (EGFR) signaling in SARS coronavirus-induced pulmonary fibrosis

“…Cancer patients treated with tyrosine kinase inhibitors show an increased incidence of interstitial lung disease (ILD) which is often a precursor to pulmonary fibrosis (Kato and Nishio, 2006). Similar association with ILD were also seen in patients treated with an anti-EGFR monoclonal antibody, Panitumumab (Osawa et al, 2015;Yamada et al, 2013). Gefitinib also exacerbates pulmonary fibrosis induced by bleomycin in mice (Suzuki et al, 2003).…”

Clinical Pharmacokinetics and Pharmacodynamics of the Epidermal Growth Factor Receptor Inhibitor Panitumumab in the Treatment of Colorectal Cancer

“…The reason for this is unclear, but possible explanations could be genetic susceptibility, different clinical practices or environmental factors, detection bias, and reporting bias. A postmarketing analysis in Japan showed an incidence of ILD of 1.3% (39 of 3085 patients), with a high mortality rate of 51.3% (20 of 39 cases) [88]. The following risk factors for ILD were identified: male sex, older than 65 years of age, a history of ILD, poor general condition, and no history of previous drug treatment for CRC (including cetuximab).…”

Cetuximab‐associated pulmonary toxicity in concurrent chemoradiation for the treatment of a squamous cell carcinoma of the head and neck

“…Of these patients, 6 developed noninfection‐related ILD. A post marketing surveillance studies has also illustrated the rare development of severe pulmonary toxicity with another monoclonal antibody named Panitumumab, used as treatment for recurrent colorectal cancer . An analysis of 3058 patients who were treated for colorectal cancer in Japan demonstrated a 1.5% incidence of ILD and 15.3% mortality rate due to this severe side effect.…”