Real-World Treatment Sequencing, Toxicities, Health Utilities, and Survival Outcomes in Patients with Advanced ALK-Rearranged Non-Small-Cell Lung Cancer.

Schmid, Sabine; Cheng, Sierra; Chotai, Simren; Garcia, Miguel; Zhan, Luna; Hueniken, Katrina; Balaratnam, Karmugi; Khan, Khaleeq; Patel, Devalben; Grant, Benjamin; Raptis, Roula; Brown, M Catherine; Xu, Wei; Moriarty, Patrick; Shepherd, Frances A; Sacher, Adrian G; Leighl, Natasha B; Bradbury, Penelope A; Liu, Geoffrey (2023). Real-World Treatment Sequencing, Toxicities, Health Utilities, and Survival Outcomes in Patients with Advanced ALK-Rearranged Non-Small-Cell Lung Cancer. Clinical lung cancer, 24(1), pp. 40-50. Elsevier 10.1016/j.cllc.2022.09.007

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OBJECTIVES

This real-world analysis describes treatment patterns, sequencing and clinical effectiveness, toxicities, and health utility outcomes in advanced-stage, incurable ALK-positive NSCLC patients across five different ALK-TKIs.

MATERIALS AND METHODS

Clinicodemographic, treatment, and toxicity data were collected retrospectively in patients with advanced-stage ALK-positive NSCLC at Princess Margaret Cancer Centre. Patient-reported symptoms, toxicities, and health utilities were collected prospectively.

RESULTS

Of 148 ALK-positive NSCLC patients seen July 2009-May 2021, median age was 58.9 years; 84 (57%) were female; 112 (76%) never-smokers; 54 (47%) Asian and 40 (35%) white; 139 (94%) received at least one ALK-TKI: crizotinib (n = 74; 54%) and alectinib (n = 61; 44%) were administered mainly as first-line ALK-TKI, ceritinib, brigatinib and lorlatinib were administered primarily after previous ALK-TKI failure. Median overall survival (OS) was 54.0 months; 31 (21%) patients died within two years of advanced-stage diagnosis. Treatment modifications were observed in 35 (47%) patients with crizotinib, 19 (61%) with ceritinib, 41 (39%) with alectinib, 9 (41%) with brigatinib and 8 (30%) with lorlatinib. Prevalence of dose modifications and self-reported toxicities were higher with early versus later generation ALK-TKIs (P<.05). The presence of early treatment modification was not negatively associated with progression-free survival (PFS) and OS analyses.

CONCLUSION

Serial ALK-TKI sequencing approaches are viable therapeutic options that can extend quality of life and quantity-of-life, though a fifth of patients died within two years. No best single sequencing approach could be determined. Clinically relevant toxicities occurred across all ALK-TKIs. Treatment modifications due to toxicity may not necessarily compromise outcomes, allowing multiple approaches to deal with ALK-TKI toxicities.

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