1302P - Lorlatinib in patients with ALK+ NSCLC treated beyond initial disease progression

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) Table: 1302P

*ITT population with CNS metastases.

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.

Editorial acknowledgement

Medical writing support was provided by Paul O’Neill, PhD, of CMC Affinity, McCann Health Medical Communications, and was funded by Pfizer Inc.

Legal entity responsible for the study

Pfizer Inc.

Funding

Pfizer Inc.

Disclosure

S.I. Ou: Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: Pfizer Inc.; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: Roche/Genentech; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: AstraZeneca; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: Takeda/ARIAD; Advisory/Consultancy: Daiichi Sankyo; Shareholder/Stockholder/Stock options: Turning Point Therapeutics. B. Solomon: Advisory/Consultancy: Pfizer Inc.; Advisory/Consultancy: Novartis; Advisory/Consultancy: Roche-Genentech; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Bristol-Myers Squibb; Advisory/Consultancy: Merck; Advisory/Consultancy: Amgen; Advisory/Consultancy: Gritstone Oncology. A. Shaw: Honoraria (self), Advisory/Consultancy, Research grant/Funding (self), Travel/Accommodation/Expenses: Pfizer Inc.; Honoraria (self), Advisory/Consultancy, Research grant/Funding (self), Full/Part-time employment: Novartis; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Genentech/Roche; Honoraria (self), Advisory/Consultancy, Research grant/Funding (self): Ariad/Takeda; Honoraria (self), Advisory/Consultancy, Research grant/Funding (self): Ignyta; Honoraria (self), Advisory/Consultancy: Loxo; Honoraria (self), Advisory/Consultancy: Bayer; Honoraria (self), Advisory/Consultancy: Chugai; Honoraria (self), Advisory/Consultancy: Blueprint Medicines; Honoraria (self), Advisory/Consultancy: KSQ Therapeutics; Honoraria (self), Advisory/Consultancy: Daiichi Sankyo; Honoraria (self), Advisory/Consultancy: EMD Serono; Honoraria (self), Advisory/Consultancy: Taiho Pharmaceutical; Honoraria (self), Advisory/Consultancy, Research grant/Funding (self): TP Therapeutics; Honoraria (self), Advisory/Consultancy: Servier; Honoraria (self), Advisory/Consultancy: Syros; Honoraria (self), Advisory/Consultancy: Foundation Medicine; Honoraria (self), Advisory/Consultancy: Guardant; Honoraria (self), Advisory/Consultancy: Natera; Honoraria (self), Advisory/Consultancy: Achilles; Honoraria (self), Advisory/Consultancy: Archer. S.M. Gadgeel: Advisory/Consultancy, Travel/Accommodation/Expenses: Roche/Genentech; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Takeda; Advisory/Consultancy: Novartis; Advisory/Consultancy: Daiichi Sankyo; Advisory/Consultancy: Pharmar; Honoraria (self), Travel/Accommodation/Expenses: Merck. B. Besse: Research grant/Funding (self): Gustave Roussy Cancer Center; Research grant/Funding (self): AbbVie; Research grant/Funding (self): Amgen; Research grant/Funding (self): AstraZeneca; Research grant/Funding (self): BeiGene; Research grant/Funding (self): Blueprint Medicines; Research grant/Funding (self): BMS; Research grant/Funding (self): Boehringer Ingelheim; Research grant/Funding (self): Celgene; Research grant/Funding (self): Cristal Therapeutics; Research grant/Funding (self): Daiichi Sankyo; Research grant/Funding (self): Eli Lilly; Research grant/Funding (self): GSK; Research grant/Funding (self): Ignyta; Research grant/Funding (self): Ipsen; Research grant/Funding (self): Inivata; Research grant/Funding (self): Janssen; Research grant/Funding (self): Merck KGaA; Research grant/Funding (self): MSD; Research grant/Funding (self): Nektar; Research grant/Funding (self): Onxeo; Research grant/Funding (self): OSE immunotherapeutics; Research grant/Funding (self): Pfizer Inc.; Research grant/Funding (self): PharmaMar; Research grant/Funding (self): Roche-Genentech; Research grant/Funding (self): Sanofi; Research grant/Funding (self): Servier; Research grant/Funding (self): Spectrum Pharmaceuticals; Research grant/Funding (self): Takeda; Research grant/Funding (self): Tiziana Pharma; Tolero Pharmaceuticals. R.A. Soo: Research grant/Funding (self), Travel/Accommodation/Expenses: AstraZeneca; Research grant/Funding (self), Travel/Accommodation/Expenses: Boehringer Ingelheim; Travel/Accommodation/Expenses, Personal fees : Bristol-Myers Squibb; Travel/Accommodation/Expenses, Personal fees : Eli Lilly; Travel/Accommodation/Expenses, Personal fees : Merck; Travel/Accommodation/Expenses, Personal fees : Novartis; Travel/Accommodation/Expenses, Personal fees : Pfizer Inc.; Travel/Accommodation/Expenses, Personal fees : Roche; Travel/Accommodation/Expenses, Personal fees : Taiho; Travel/Accommodation/Expenses, Personal fees: Takeda; Travel/Accommodation/Expenses, Personal fees : Yuhan; Travel/Accommodation/Expenses, Personal fees : Amgen. A. Abbattista: Full/Part-time employment: Pfizer Inc. H. Thurm: Shareholder/Stockholder/Stock options, Full/Part-time employment: Pfizer Inc. F. Toffalorio: Full/Part-time employment: Pfizer Inc. R.J. Wiltshire: Shareholder/Stockholder/Stock options, Full/Part-time employment: Pfizer Inc. A. Bearz: Advisory/Consultancy, Speaker Bureau/Expert testimony: Takeda; Advisory/Consultancy, Speaker Bureau/Expert testimony: Boehringer Ingelheim; Advisory/Consultancy, Speaker Bureau/Expert testimony: Novartis; Advisory/Consultancy, Speaker Bureau/Expert testimony: Pfizer Inc.; Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: MSD; Travel/Accommodation/Expenses: Jansen; Travel/Accommodation/Expenses: Roche; Travel/Accommodation/Expenses: BMS.