Interstitial Lung Abnormalities Impact OS in NSCLC Patients Receiving CRT, Adjuvant Durvalumab

Pretreatment interstitial lung abnormalities were associated with worse overall and cause-specific survival in Japanese patients receiving chemoradiotherapy followed by adjuvant durvalumab for locally advanced non–small-cell lung cancer.

The presence of pretreatment interstitial lung abnormality (ILA) was associated with shorter overall survival (OS) in a study of Asian patients receiving chemoradiotherapy (CRT) followed by adjuvant durvalumab for locally advanced non–small-cell lung cancer (NSCLC).

Patients with advanced NSCLC who have ILA at baseline are at a higher risk of radiation pneumonitis, a condition associated with worse prognosis for patients receiving concurrent CRT (cCRT) followed by consolidation therapy with durvalumab—the current standard of care for locally advanced, unresectable NSCLC. Durvalumab was FDA approved in this population in 2018 based on results from an interim analysis of the randomized, phase 3 PACIFIC trial (NCT02125461).

Real-world data confirming the PACIFIC findings have since been reported, but large-scale real-world data on Asian patients are lacking, study authors Tairo Kashihara, et al., wrote. The new study, published in the journal Radiotherapy and Oncology, examined prognostic factors in Japanese patients treated with cCRT and adjuvant durvalumab.

A total of 113 Japanese patients who received definitive cCRT and adjuvant durvalumab for locally advanced NSCLC were included in the study, which is the largest real-world data set of Japanese patients in Asia, according to the study authors. ILA scores were determined by at least one radiation oncologist and a radiologist in the most recent diagnostic CT scan ahead of cCRT initiation. A score of 0 indicated no interstitial lung changes; 1 was defined as ILAs without honeycombing; and 2 indicated ILAs with honeycombing. A total of 96 patients (85%) had an ILA score of 0, and the rest had an ILA score of 1 at baseline.

All 17 patients who had an ILA score of 1 did not complete a full year of durvalumab. In the overall patient group, 20 patients total (17.7%) discontinued durvalumab due to interstitial pneumonia, while 9 patients in the ILA score 1 group (52.9%) discontinued durvalumab due to interstitial pneumonia.

In a multivariate analysis, baseline factors associated with OS were ILA scores, adenocarcinoma, and Eastern Cooperative Oncology Group (ECOG) performance status at the time of durvalumab initiation. In the ILA score 0 group, the 2-year survival rate was 82.4%, versus 37.8% in the ILA score 1 cohort. Patients with adenocarcinoma had a 2-year survival rate of 85.5%, whereas others had a 2-year survival of 65.7%. In patients with an ECOG performance status of 0, the survival rate was 82.3%, while those with a performance status of 1 had a 64.1% survival rate at 2 years.

Pretreatment ILA status was also associated with cause-specific survival, as was PD-L1 status. A PD-L1 tumor proportion score of 1% or higher was prognostic for progression-free survival and in-field progression-free survival.

Contrary to a cohort study conducted in the United States, the study found that there was a similar benefit from durvalumab even when the time from CRT to durvalumab initiation was longer, the authors noted. This finding suggests there might be more of a benefit to starting durvalumab when a patient has improved performance status and tumor immune environment characteristics versus starting durvalumab earlier.

The correlation between ILA scores and OS may be due to the known risk of severe radiation pneumonitis in this population, the authors wrote. Prior reports have suggested that ILA score is useful for prediction of radiation pneumonia following radiotherapy, and patients with ILA 1 in the current study cohort were much more likely to discontinue durvalumab due to interstitial pneumonia. Patients with interstitial pneumonia also have fewer treatment options for relapse, which may be another reason for poorer outcomes in this patient population.

Reference

Kashihara T, Nakayama Y, Okuma K, et al. Impact of interstitial lung abnormality on survival after adjuvant durvalumab with chemoradiotherapy for locally advanced non-small cell lung cancer. Radiother Oncol. Published online January 11, 2023. doi:10.1016/j.radonc.2022.109454

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