Randomized Trial Evaluates Radiation Pneumonitis Risk After Immunotherapy, Chemoradiation in Stage III NSCLC

Patients with unresectable stage IIIA or IIIB non-small cell lung cancer (NSCLC) who are treated with nivolumab or combination nivolumab and ipilimumab after concurrent chemoradiation therapy (CCRT), experience a higher risk of radiation pneumonitis if they receive a radiation dose of 20 Gy > 23% in both lungs, according to a recent study.

Michael Weisman, MD, of the Indiana University School of Medicine, and colleagues, analyzed data from the randomized phase 2 BTCRC-LUN-16-081 trial and published their findings in the Internation Journal of Radiation Oncology, Biology, Physics.

The BTCRC-LUN-16-081 trial assessed the efficacy and tolerability of consolidative nivolumab versus nivolumab plus ipilimumab for six months. The analysis by Dr. Weisman and colleagues evaluated radiation dose parameters, patient demographics, and toxicity events to further identify the risk and severity of pneumonitis among study participants.

The researchers analyzed 105 patients across two treatment groups, with 51 patients receiving combination nivolumab and ipilimumab and 54 patients receiving nivolumab alone. Of the 104 patients who had available dose-volume histograms for evaluation, 65 patients had stage IIIA NSCLC and 39 patients had stage IIIB NSCLC. The investigators used the American Journal Committee on Cancer, seventh edition, to assess disease stage of the patients.

The results showed that 29 patients (27.9%) were diagnosed with grade 2 or greater pneumonitis. To explore the correlation of the study findings with radiation dose distribution, the investigators used logistic regression and evaluated “different cutoffs for percentage of normal lung volume receiving at least 20 Gy (V20).” The results showed that patients with V20 > 23% “demonstrated significantly higher grade 2 or greater pneumonitis rates (37.1% vs 16.2%, P=.031).”

Moreover, the findings demonstrated no significant differences in the rate of radiation pneumonitis between the patients receiving nivolumab or combination nivolumab and ipilimumab. In addition, the researchers showed that “traditional lung dose-volume histogram cutoffs (percentage of normal lung volume receiving at least five Gy (V5) > 65%, V20 > 35%, and mean > 20 Gy) were not associated with pneumonitis.”

Based on these results, Dr. Weisman and colleagues noted that radiation dose constraints for lungs after consolidative immunotherapy and CCRT should continue to be “evaluated and optimized when feasible.” They also stated that additional approaches focused on improved outcomes and reduced treatment-related toxicity for patients with stage III NSCLC are needed.

“In patients receiving nivolumab or nivolumab plus ipilimumab after definitive CCRT, lung V20 > 23% was associated with an increased risk of grade 2 or greater pneumonitis,” the researchers concluded.

Source: International Journal of Radiation Oncology, Biology, Physics