nintedanib and Small-Cell-Lung-Carcinoma

Nintedanib is an oral triple angiokinase inhibitor. This study was conducted to evaluate the efficacy and safety of nintedanib in patients (pts) with relapsed/refractory small cell lung cancer (SCLC).. Pts with an ECOG PS from 0 to 2 who exhibited progression after one or two prior chemotherapy or chemo/radiotherapy were enrolled. Pts received nintedanib 200mg BID daily in a 4-week cycle until progression or intolerable toxicity. The primary end point was the objective response rate (ORR). A two-stage design was employed. To continue to stage 2, ≥2 responders out of 22 pts were required.. From Dec 2011 to June 2014, 24 pts were enrolled. Twenty-two pts completed treatment and were evaluable for response. The median follow-up was 9.7 (0.5-19.8) months. The median age was 64 (46-77) years. Twenty-two pts were male. Six pts had sensitive relapse. Eight pts received one prior chemotherapy. A median of one (range 1-5) cycle was administered. One pt had a partial response, and seven pts exhibited stable disease. The ORR was 5% (95% confidence interval [CI], 0.1-22.8). Median progression-free survival was 1.0 (95% CI, 0.9-1.1) month, and overall survival was 9.8 (95% CI, 8.4-11.2) months. The response criteria to proceed to full accrual were not met. The most frequent drug-related adverse events (AE) included hepatic enzyme elevation (86%), anemia (73%), anorexia (59%), and nausea (50%). Most AEs were mild and manageable. Grade 3 hepatic enzyme elevation occurred in 5 pts (23%).. Nintedanib exhibited only limited activity with a manageable AE profile in relapsed or refractory SCLC (NCT01441297).

Topics: Aged; Antineoplastic Agents; Disease-Free Survival; Female; Humans; Indoles; Male; Middle Aged; Neoplasm Recurrence, Local; Small Cell Lung Carcinoma; Treatment Outcome

Nintedanib is a tyrosine kinase inhibitor that efficiently slows the progression of idiopathic pulmonary fibrosis (IPF) and has an acceptable tolerability profile. In contrast, immune checkpoint inhibitors (ICIs) such as programmed death 1 and programmed death ligand 1 inhibitors have shown clinical activity and marked efficacy in the treatment of non-small cell lung cancer. However, it is unclear whether nintedanib reduces the risk of ICI-induced pneumonitis in IPF.. A 78-year-old man with squamous cell lung carcinoma in IPF underwent second-line treatment with pembrolizumab. He was diagnosed as having pembrolizumab-induced pneumonitis after two cycles. He was administered prednisolone (PSL) and then improved immediately. Thereafter, his lung cancer lesion enlarged despite treatment with TS-1. Atezolizumab was then administered as 4th-line chemotherapy, but he immediately developed atezolizumab-induced pneumonitis after 1 cycle. The re-escalated dosage of PSL improved the pneumonitis, and then nintedanib was started as additional therapy. Under careful observation with nintedanib, atezolizumab was re-administered on day 1 of an every-21-day cycle. After three cycles, it remained stable without exacerbation of drug-induced pneumonitis.. This case indicates the possibility that the addition of nintedanib to ICI therapy might prevent drug-induced pneumonitis or acute exacerbation of IPF. However, whether anti-fibrotic agents such as nintedanib are actually effective in preventing ICI-induced pneumonitis in ILD remains unknown and additional research is greatly needed to identify effective therapies for ILD combined with lung cancer.

Topics: Aged; Antibodies, Monoclonal, Humanized; Carcinoma, Non-Small-Cell Lung; Disease Progression; Humans; Idiopathic Pulmonary Fibrosis; Indoles; Lung Neoplasms; Male; Pneumonia; Protein Kinase Inhibitors; Retreatment; Small Cell Lung Carcinoma; Tomography, X-Ray Computed

Topics: Antibodies, Monoclonal; Antineoplastic Agents; Breast Neoplasms; Carcinoma, Non-Small-Cell Lung; Docetaxel; Erlotinib Hydrochloride; Female; Humans; Imidazoles; Indoles; Lung Neoplasms; Male; Medical Oncology; Multicenter Studies as Topic; Oximes; Protein Kinase Inhibitors; Pyrimidines; Pyrroles; Quinazolines; Randomized Controlled Trials as Topic; Small Cell Lung Carcinoma; Societies, Medical; Sulfones; Sunitinib; Taxoids; Treatment Outcome; Triazoles; United States