Lorlatinib in patients with ALK+ NSCLC treated beyond initial disease progression

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Conference Proceeding

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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.



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