Efficacy and safety of lorlatinib in patients with ALK- and ROS1-rearranged metastatic non-small cell lung cancer treated within the compassionate use program in Spain
Antonio Calles , Mirian Alonso , Paloma Martín-Martorell , Ana Gómez , Javier de Castro , Maite Martínez-Aguillo , Anna Estival , Joaquin Mosquera , Natividad Martínez-Banaclocha , Margarita Majem , Roxana Reyes , Eider Azkona , Ana Laura Ortega , Santiago Aguin , Ana Santos , Andrés Aguilar , Marc Cucurull , Ana Blasco , Virginia Calvo , Dolores Isla , Javier Baena
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引用次数: 0
Abstract
Background
Lorlatinib, a third-generation tyrosine kinase inhibitor (TKI), targets both ALK and ROS1 rearrangements in non-small cell lung cancer (NSCLC). It is approved for ALK-positive patients after progression on prior TKIs but lacks FDA or EMA approval for ROS1-positive NSCLC. This study evaluates lorlatinib's efficacy and safety in both ALK- and ROS1-positive patients through a compassionate use program in Spain.
Methods
We analyzed ALK-positive patients treated from November 2016 to February 2019 and ROS1-positive patients treated from November 2016 to March 2021. Eligible patients had Stage IV NSCLC with confirmed ALK or ROS1 rearrangements and prior TKI therapy. For ALK-positive patients, at least two prior TKIs were required if crizotinib was used first. For ROS1-positive patients, prior crizotinib was required.
Results
In 61 ALK-positive patients, 59 % had brain metastasis, and 85.2 % received at least two prior ALK TKIs. The overall response rate (ORR) was 32.8 %, with a median progression-free survival (PFS) of 11.2 months. Intracranial ORR was 47.6 %, with higher efficacy in patients with evaluable brain metastasis. In patients with 1, 2, or ≥3 lines of previous TKIs, we observed a median PFS of 15.1, 11.1 and 7.6 months, respectively. Among 42 ROS1-positive patients, 59 % had brain metastasis, and 61.9 % received ≥2 prior therapies. The confirmed ORR was 47.6 %, with 16.7 % complete responses. Median PFS was 10 months. Patients receiving crizotinib alone had a median PFS of 10 months, while those with two prior TKIs had a median PFS of 8.5 months. Intracranial response was 44.4 %, rising to 57.1 % in patients evaluable with brain metastasis. No new safety signals were observed.
Conclusion
Lorlatinib demonstrated consistent efficacy and manageable safety in both ALK- and ROS1-positive NSCLC patients treated under the compassionate use program in Spain. These real-world findings support its use as an effective treatment option in heavily pretreated patients.
MicroAbstract
We evaluated the efficacy and safety of lorlatinib in ALK- and ROS1-positive NSCLC patients within a compassionate use program in Spain. Among 61 ALK-positive patients, including 59 % with brain metastasis and 85.2 % treated with at least 2 prior ALK TKIs, lorlatinib achieved a confirmed overall response rate (ORR) of 32.8 % and a median progression-free survival (PFS) of 11.2 months. In 42 ROS1-positive patients previously treated with crizotinib, lorlatinib showed an ORR of 47.6 % and a median PFS of 10 months, confirming its clinical activity despite the lack of FDA or EMA approval for this indication.
期刊介绍:
Cancer Treatment and Research Communications is an international peer-reviewed publication dedicated to providing comprehensive basic, translational, and clinical oncology research. The journal is devoted to articles on detection, diagnosis, prevention, policy, and treatment of cancer and provides a global forum for the nurturing and development of future generations of oncology scientists. Cancer Treatment and Research Communications publishes comprehensive reviews and original studies describing various aspects of basic through clinical research of all tumor types. The journal also accepts clinical studies in oncology, with an emphasis on prospective early phase clinical trials. Specific areas of interest include basic, translational, and clinical research and mechanistic approaches; cancer biology; molecular carcinogenesis; genetics and genomics; stem cell and developmental biology; immunology; molecular and cellular oncology; systems biology; drug sensitivity and resistance; gene and antisense therapy; pathology, markers, and prognostic indicators; chemoprevention strategies; multimodality therapy; cancer policy; and integration of various approaches. Our mission is to be the premier source of relevant information through promoting excellence in research and facilitating the timely translation of that science to health care and clinical practice.