Chemotherapy plus nintedanib has ‘promising’ efficacy in small cell lung cancer with IPF

Key takeaways:

• A pharmacotherapy is needed for patients with small cell lung cancer plus IPF.
• Patients frequently experienced grade 3 or greater neutropenia, leukopenia and thrombocytopenia with chemotherapy plus nintedanib.

In a study of patients with small cell lung cancer and idiopathic pulmonary fibrosis receiving carboplatin, etoposide and nintedanib, the primary endpoint was met, according to results published in Annals of the American Thoracic Society.

At 28 days after the final administration of cytotoxic chemotherapy, the incidence of acute exacerbations of IPF did not cross the prespecified statistical threshold, according to researchers.

“A fatal acute exacerbation occasionally develops during chemotherapy for small-cell lung cancer (SCLC) with comorbid interstitial pneumonia (IP),” Satoshi Ikeda, MD, PhD, chief physician of the department of respiratory medicine at Kanagawa Cardiovascular and Respiratory Center in Japan, told Healio.

Patients with comorbid IP are excluded from most pivotal trials of the standard of care for lung cancer, so the need to establish safe and effective pharmacotherapy is urgent, especially for SCLC with comorbid IPF, Ikeda continued.

“In recent years, the addition of anti-PD-L1 antibody to platinum plus etoposide has become the standard first-line treatment for ED-SCLC,” Ikeda said. “However, a high risk of immune checkpoint inhibitor-induced pneumonitis has been reported in patients with comorbid IP.”

In the multicenter, single-arm, phase 2 NEXT-SHIP study, Ikeda and colleagues evaluated 33 patients (median age, 73 years; 87.9% men; median percentage FVC, 85.2%) with unresectable SCLC and IPF to determine the impact of carboplatin and etoposide (cytotoxic chemotherapy) every 3 weeks plus twice-daily 150 mg nintedanib (Ofev, Boehringer Ingelheim) on IPF-acute exacerbation incidence on the 28th day since the last administration of cytotoxic chemotherapy.

Researchers also captured data on adverse events to report on drug safety.

Within the total cohort, 51.5% (n = 17) had honeycomb lungs.

In terms of therapy delivery during the 10.5-month median observation period, receipt of four cycles of cytotoxic chemotherapy was reported in 29 patients (87.9%) and receipt of maintenance nintedanib was reported in 26 patients (78.8%; median length, 5.4 months).

Disease progression was the reported reason behind treatment discontinuation for 28 patients, according to researchers.

The prespecified statistical threshold for acute exacerbation of IPF incidence was 20%, and this was not crossed at 28 days after the final administration of cytotoxic chemotherapy with a 3% (95% CI, 0.2%-13.6%) incidence.

When considering the full observation period, researchers found a 12.1% incidence of this outcome.

Due to one consent withdrawal, other efficacy outcomes, such as response rate and survival, were assessed in 32 patients.

In this set of patients, researchers observed a 68.8% objective response rate. Additionally, the median overall survival (OS) length (13.4 months) was longer than the median progression-free survival length (4.2 months).

“Although no definitive conclusions can be drawn in this study without a control arm, the suppression of fatal IPF-[acute exacerbation] by the combination of nintedanib may have contributed to the favorable OS,” Ikeda and colleagues wrote.

Grading adverse events according to the Common Terminology Criteria for Adverse Events revealed that patients frequently experienced grade 3 or greater neutropenia (81.8%), leukopenia (39.4%) and thrombocytopenia (30.3%).

Only one adverse event (acute exacerbation of IPF) was considered a grade 5 event.

“This NEXT-SHIP study met the primary endpoint regarding the incidence of IPF-[acute exacerbation] with promising results for efficacy,” Ikeda told Healio. “Carboplatin, etoposide and nintedanib combination therapy may be one of the standard treatment options for SCLC with comorbid IPF.

“No definitive conclusion can be drawn from this study alone due to the small sample size and single-arm design,” Ikeda added. “Therefore, further validation through randomized trials involving a larger number of patients is desirable.”