Efficacy of lorlatinib in lung carcinomas carrying distinct ALK translocation variants: The results of a single-center study.

ALK rearrangements Brain metastases Lorlatinib Non-small cell lung cancer Review

Journal

Translational oncology
ISSN: 1936-5233
Titre abrégé: Transl Oncol
Pays: United States
ID NLM: 101472619

Informations de publication

Date de publication:
Aug 2021
Historique:
received: 03 02 2021
revised: 01 05 2021
accepted: 07 05 2021
pubmed: 25 5 2021
medline: 25 5 2021
entrez: 24 5 2021
Statut: ppublish

Résumé

Lorlatinib is a novel potent ALK inhibitor, with only a few studies reporting the results of its clinical use. This study describes the outcomes of lorlatinib treatment for 35 non-small cell lung cancer patients with ALK rearrangements, who had 2 (n = 5), 1 (n = 26) or none (n = 4) prior tyrosine kinase inhibitors and received lorlatinib mainly within the compassionate use program. Objective tumor response (OR) and disease control (DC) were registered in 15/35 (43%) and 33/35 (94%) patients, respectively; brain metastases were particularly responsive to the treatment (OR: 22/27 (81%); DC: 27/27 (100%)). Median progression free survival (PFS) was estimated to be 21.8 months, and median overall survival (OS) approached to 70.1 months. Only 4 out of 35 patients experienced no adverse effects; two of them were the only subjects who had no clinical benefit from lorlatinib. PFS and OS in the no-adverse-events lorlatinib users were strikingly lower as compared to the remaining patients (1.1 months vs. 23.7 months and 10.5 months vs. not reached, respectively; p < 0.0001 for both comparisons). ALK translocation variants were known for 28 patients; there was no statistical difference between patients with V.1 and V.3 rearrangements with regard to the OS or PFS. Use of lorlatinib results in excellent disease outcomes, however caution must be taken for patients experiencing no adverse effects from this drug.

Sections du résumé

BACKGROUND BACKGROUND
Lorlatinib is a novel potent ALK inhibitor, with only a few studies reporting the results of its clinical use.
METHODS METHODS
This study describes the outcomes of lorlatinib treatment for 35 non-small cell lung cancer patients with ALK rearrangements, who had 2 (n = 5), 1 (n = 26) or none (n = 4) prior tyrosine kinase inhibitors and received lorlatinib mainly within the compassionate use program.
RESULTS RESULTS
Objective tumor response (OR) and disease control (DC) were registered in 15/35 (43%) and 33/35 (94%) patients, respectively; brain metastases were particularly responsive to the treatment (OR: 22/27 (81%); DC: 27/27 (100%)). Median progression free survival (PFS) was estimated to be 21.8 months, and median overall survival (OS) approached to 70.1 months. Only 4 out of 35 patients experienced no adverse effects; two of them were the only subjects who had no clinical benefit from lorlatinib. PFS and OS in the no-adverse-events lorlatinib users were strikingly lower as compared to the remaining patients (1.1 months vs. 23.7 months and 10.5 months vs. not reached, respectively; p < 0.0001 for both comparisons). ALK translocation variants were known for 28 patients; there was no statistical difference between patients with V.1 and V.3 rearrangements with regard to the OS or PFS.
CONCLUSION CONCLUSIONS
Use of lorlatinib results in excellent disease outcomes, however caution must be taken for patients experiencing no adverse effects from this drug.

Identifiants

pubmed: 34030112
pii: S1936-5233(21)00113-3
doi: 10.1016/j.tranon.2021.101121
pmc: PMC8144735
pii:
doi:

Types de publication

Journal Article

Langues

eng

Pagination

101121

Informations de copyright

Copyright © 2021. Published by Elsevier Inc.

Auteurs

Sergey V Orlov (SV)

I.P. Pavlov St.-Petersburg State Medical University, St.-Petersburg 197022, Russia; Institute of Medical Primatology, Sochi 354376, Russia.

Aglaya G Iyevleva (AG)

N.N. Petrov Institute of Oncology, St.-Petersburg 197758, Russia; St.-Petersburg State Pediatric Medical University, St.-Petersburg 194100, Russia. Electronic address: aglayai@inbox.ru.

Elena A Filippova (EA)

I.P. Pavlov St.-Petersburg State Medical University, St.-Petersburg 197022, Russia.

Alexandra M Lozhkina (AM)

I.P. Pavlov St.-Petersburg State Medical University, St.-Petersburg 197022, Russia.

Svetlana V Odintsova (SV)

I.P. Pavlov St.-Petersburg State Medical University, St.-Petersburg 197022, Russia.

Tatiana N Sokolova (TN)

N.N. Petrov Institute of Oncology, St.-Petersburg 197758, Russia.

Natalia V Mitiushkina (NV)

N.N. Petrov Institute of Oncology, St.-Petersburg 197758, Russia.

Vladislav I Tiurin (VI)

N.N. Petrov Institute of Oncology, St.-Petersburg 197758, Russia; St.-Petersburg State Pediatric Medical University, St.-Petersburg 194100, Russia.

Elena V Preobrazhenskaya (EV)

N.N. Petrov Institute of Oncology, St.-Petersburg 197758, Russia; St.-Petersburg State Pediatric Medical University, St.-Petersburg 194100, Russia.

Alexandr A Romanko (AA)

N.N. Petrov Institute of Oncology, St.-Petersburg 197758, Russia; St.-Petersburg State Pediatric Medical University, St.-Petersburg 194100, Russia.

Alexandr S Martianov (AS)

N.N. Petrov Institute of Oncology, St.-Petersburg 197758, Russia; St.-Petersburg State Pediatric Medical University, St.-Petersburg 194100, Russia.

Alexandr O Ivantsov (AO)

N.N. Petrov Institute of Oncology, St.-Petersburg 197758, Russia; St.-Petersburg State Pediatric Medical University, St.-Petersburg 194100, Russia.

Svetlana N Aleksakhina (SN)

N.N. Petrov Institute of Oncology, St.-Petersburg 197758, Russia; St.-Petersburg State Pediatric Medical University, St.-Petersburg 194100, Russia.

Alexandr V Togo (AV)

N.N. Petrov Institute of Oncology, St.-Petersburg 197758, Russia; St.-Petersburg State Pediatric Medical University, St.-Petersburg 194100, Russia.

Evgeny N Imyanitov (EN)

I.P. Pavlov St.-Petersburg State Medical University, St.-Petersburg 197022, Russia; Institute of Medical Primatology, Sochi 354376, Russia; N.N. Petrov Institute of Oncology, St.-Petersburg 197758, Russia; St.-Petersburg State Pediatric Medical University, St.-Petersburg 194100, Russia; I.I. Mechnikov North-Western Medical University, St.-Petersburg 191015, Russia.

Classifications MeSH