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Consolidation ALK Tyrosine Kinase Inhibitors versus Durvalumab or Observation After Chemoradiation in Unresectable Stage III ALK+ Non-Small Cell Lung Cancer.

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Consolidation ALK Tyrosine Kinase Inhibitors versus Durvalumab or Observation After Chemoradiation in Unresectable Stage III ALK+ Non-Small Cell Lung Cancer. Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer Nassar, A. H., Jayakrishnan, R., Feng, J., Shepherd, F., Adib, E., Cheung, J. M., Lin, J. J., Liu, Y., Lin, S. H., Parikh, K., Sridhar, A., Shakya, P., Dilling, T. J., Kaldas, D., Gray, J. E., Lobachov, A., Bar, J., Luders, H., Grohe, C., Gupta, S., Leal, T., Fitzgerald, B., Crowley, F., Fujiwara, Y., Marron, T. U., Wilgucki, M., Reuss, J., Chen, L., Sankar, K., Aredo, J. V., Neal, J. W., Wakelee, H. A., Thummalapalli, R., Yu, H., Whitaker, R., Velazquez, A., Ragavan, M., Cortellini, A., Kwiatkowski, D. J., Naqash, A. R., Goldberg, S. B., Kim, S. Y. 2024

Abstract

Patients with advanced ALK-positive non-small cell lung cancer (NSCLC) typically have poor response to immunotherapy; the benefit of consolidation durvalumab in patients with unresectable stage III ALK-positive NSCLC remains unclear. Herein, we compare the efficacy and safety of consolidation ALK tyrosine kinase inhibitor (TKI) versus durvalumab or observation after concurrent chemoradiation (cCRT).We conducted a retrospective study using a multi-center study of 17 institutions globally. Patients with unresectable stage III ALK-positive NSCLC treated between 2015-2022 were included. Patients received ALK TKI, durvalumab, or observation after cCRT. Real-world progression-free survival (rwPFS) and overall survival (OS) were estimated using Kaplan-Meier method. Treatment-related adverse events (trAE) were classified by Common Terminology Criteria for Adverse Events v5.0. Outcomes were assessed by multivariable Cox regression analysis.Sixty-seven patients were included, of whom 39 (58%) were female. Median age was 57 years (IQR: 49-67). Fifteen received consolidation ALK TKI, 30 received durvalumab, and 22 underwent observation. Baseline characteristics were similar across the 3 groups other than differences in race. After adjusting for stage, age, and nodal status, median rwPFS was significantly longer for ALK TKI (rwPFS not reached [NR], 95% CI 22.7-NR) versus durvalumab (11.3 months, 95% CI 8.9-18.5, hazard ratio [HR]=0.12, 95% CI: 0.026-0.5, p-adjusted=0.006) or observation (7.2 months, 95% CI 3.4-10.6, HR=0.04, 95% CI: 0.009-0.2, p-adjusted<0.0001). Durvalumab significantly improved median rwPFS compared to observation (HR=0.37, 95% CI: 0.19-0.71, p-adj = 0.002, p-adjusted=0.002). Median OS in the ALK TKI and durvalumab cohorts was significantly improved compared to patients on observation (ALK TKI-observation: p=0.04; durvalumab-observation: p=0.03). TrAE of any grade occurred in 8 (53%) and 11 (37%) patients treated with ALK-TKI and durvalumab, respectively. Grade =3 trAEs occurred in 27% (n=4) of patients treated with ALK TKI and 6.7% of patients treated with durvalumab.Patients with ALK-positive NSCLC experience significantly improved rwPFS when treated with consolidation ALK TKI therapy, surpassing outcomes seen with either durvalumab or observation. While both ALK TKI therapy and durvalumab offer an extension in OS compared to observation alone, it appears that ALK TKI therapy is the superior choice, underscoring its pivotal role in enhancing patient survival.

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