Lorlatinib in patients with ALK+ NSCLC treated beyond initial disease progression
Ou SI, Solomon B, Shaw A, Gadgeel SM, Besse B, Soo RA, Abbattista A, Thurm H, Toffalorio F, Wiltshire RJ, and Bearz A. Lorlatinib in patients with ALK+ NSCLC treated beyond initial disease progression. Annals of Oncology 2020; 31:S842.
Annals of Oncology
Background: The third-generation tyrosine kinase inhibitor (TKI) lorlatinib showed overall and intracranial anti-tumor activity in patients with ALK+ NSCLC in the ongoing phase 2 trial NCT01970865. Efficacy was noted in treatment-naïve patients and following progression on previous ALK inhibitor therapy. This retrospective analysis investigated the potential clinical benefit of continuing lorlatinib beyond progressive disease (LBPD) in patients with ALK+ NSCLC. Methods: Patients with advanced ALK+ NSCLC were permitted to remain on study treatment after RECIST-defined disease progression if they continued to experience clinical benefit as per investigator judgment. Herein, continuation was defined as >3 weeks lorlatinib treatment after PD documentation by investigators. Patients were excluded if best overall response to initial lorlatinib was PD or indeterminate. Only patients who received prior crizotinib ± chemotherapy (Group A) or ≥1 second-generation ALK TKI ± chemotherapy (Group B) were included. Characteristics at baseline/progression, efficacy outcomes during lorlatinib treatment, and overall survival (OS) in LBPD and non-LBPD patients were assessed. Results: In total, 102 patients were included in the analysis (Table). In Group A, 21/28 patients (75.0%) continued LBPD with a median post-PD treatment duration (TD) of 11.8 months and overall TD of 32.4 months. In Group B, 56/74 patients (75.7%) continued LBPD with a median post-PD TD of 5.7 months and overall TD of 16.4 months. Median OS in Group B LBPD and non-LBPD patients was 26.5 months (95% CI: 18.7–35.5) and 14.7 months (95% CI: 9.3–38.5), respectively. Median OS in Group A LBPD was not reached (NR) and in non-LBPD was 24.4 months (95% CI: 12.1–NR) [Formula presented]. Conclusions: Majority of patients continued LBPD. Median OS was longer in LBPD vs non-LBPD groups. Further evaluations to better assess the clinical benefit of continuing treatment with lorlatinib beyond RECIST-determined progression are warranted. Clinical trial identification: NCT01970865.