Pneumonitis Risk in NSCLC Remains Uncertain, Obesity May Be Predictor

Data remain mixed on the exact impact durvalumab-induced pneumonitis has on overall survival (OS) and progression-free survival (PFS) in patients who have locally advanced non–small cell lung cancer (NSCLC), with findings from a new study showing neither outcome was affected by the inflammatory condition but that obesity was a significant predictor.

The retrospective cohort study, published in Journal of Thoracic Disease,¹ evaluated outcomes among veterans (N = 284) treated for NSCLC from December 5, 2017, through April 15, 2020 with durvalumab, a PD-L1 inhibitor, and followed until September 14, 2021. VA Informatics and Computing Infrastructure data services provided the veterans’ information, with only patients receiving chemoradiation (CRT) and at least 1 dose of durvalumab included in the final analysis. Durvalumab, the authors note, became the standard of care with CRT for unresectable disease following the PACIFIC trial. Pneumonitis, they continued, is one of the most common complications from this treatment.

Inflamed lungs | Image credit: SciePro - stock.adobe.com

“Given the high incidence of pneumonitis in this patient population and unclear impact on survival, this study evaluates the incidence of pneumonitis and survival in a large nationwide real-world cohort of United States veterans,” the authors wrote. “This will become increasingly important in order to help make decisions about continuing vs stopping durvalumab therapy in patients with pneumonitis.”

Stage III disease was most common (80.3%), followed by unknown stage (12%), stage II (7%), and stage I (<1%). Ninety-six percent of the patients were male patients; the median age at diagnosis was 68 years (range, 39-88); median body mass index (BMI) was 26 kg/m², with most patients (76%) having a BMI below 30 kg/m²; carboplatin/paclitaxel (80%) was the most common chemotherapy regimen; more than half of patients (59%) received more than 54 Gy of radiation; and most had squamous cell (46%) or adenocarcinoma (44%) histology.

Mean Charlson Comorbidity Index score at baseline was 4.6, with higher scores from this measure indicating greater mortality risk,² and among the 112 patients with recorded PD-L1 expression, 36.6% had 11% to 49% expression, 34.9% had less than 1% expression, and 28.6% had greater than 50% expression.

The most common reasons for durvalumab discontinuation were death (45%), therapy completed (35%), and disease progression (30%).

Overall, 21.5% of patients (n = 61) eventually developed clinically significant pneumonitis, with grade 2 and grade 3 pneumonitis most common, each occurring in 9% of patients; grade 5 pneumonitis was seen in 2%. However, images for 106 patients showed changes “possibly consistent with pneumonitis,” the study authors wrote.

They added that most patients who developed the inflammatory condition did not restart durvalumab, and that among the 19 patients who did restart durvalumab, 15 did not develop pneumonitis again and 2 developed pneumonitis a second time, necessitating treatment stoppage again.

OS and PFS were similar between those who did and did not develop pneumonitis:

• OS: 27.8 vs 36.9 months, respectively (P = .22)
• PFS: 14.4 vs 17.4 months (P = .38)

A subanalysis that estimated clinical and laboratory predictors of pneumonitis showed obesity (BMI ≥ 30 kg/m²) to be the lone predictor of pneumonitis (OR, 1.87; 95% CI, 1.01-3.47; P = .04). Similar results were not seen for chronic obstructive pulmonary disease severity, race, age at durvalumab start, chemotherapy regimen, and Romano comorbidity score.

Speaking to the significance of their findings, the authors noted that although their data show a higher rate of grade 5 pneumonitis vs other real-world studies, the condition’s lack of effect on OS and PFS is in line with the variability in these end points from other analyses. Further, their finding on obesity may be novel, because “obesity has not been previously evaluated as a clinical predictor of pneumonitis in this patient population.”

“Our study found there is no association between pneumonitis and risk of death up to 1 or 2 years when age, cancer stage, and comorbidities are taken into account,” they concluded. “However, durvalumab was discontinued in most patients who developed pneumonitis. Whether there will be long-term impacts on survival due to this discontinuation requires longer follow-up.”

References

1. Akkad N, Thomas TS, Luo S, Knoche E, Sanfilippo KM, Keller JW. A real-world study of pneumonitis in non-small cell lung cancer patients receiving durvalumab following concurrent chemoradiation. J Thorac Dis. 2023;15(12):6427-6435. doi:10.21037/jtd-22-1604
2. Charlson ME, Carrozzino D, Guidi J, Patierno C. Charlson Comorbidity Index: a critical review of clinimetric properties. Psychother Psychosom. 2022;91(1):8-35. doi:10.1159/000521288