Non-Small-Cell Lung Cancer (NSCLC) Harboring ALK Translocations: Clinical Characteristics and Management in a Real-Life Setting: a French Retrospective Analysis (GFPC 02–14 Study)

Auliac, J.B.; Monnet, I.; Dubos-Arvis, Catherine; Chiappa, A; Baize, Nathalie; Bota, S.; Vergnenègre, A.; Doubre, H.; Locher, C.; Bizieux, A.; Robinet, G.; Chouaïd, C.

doi:10.1007/s11523-017-0520-7

Cited by 10 publications

(5 citation statements)

References 24 publications

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“…To the best of our knowledge, it is the largest retrospective analysis, including the highest number of ALK+ NSCLC patients. [11][12][13] To summarize the role of radiological imaging methods in diagnosis and differential diagnosis of patients with ALK+ NSCLC, about 44.1% of patients had centrally, and 55.9% had peripherally localized lesions. In addition, cavitation was reported in only 7.7%, while effusion was present in about one-third of cases; 25.1% of the patients had brain metastasis and the median PFS was 14 months.…”

Section: Discussionmentioning

confidence: 99%

A multicenter, retrospective archive study of radiological and clinical features of ALK-positive non-small cell lung cancer patients and crizotinib efficacy

Kilickap,

Ozturk,

Karadurmus

et al. 2024

Medicine

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To evaluate radiological and clinical features in metastatic anaplastic lymphoma kinase+ non-small cell lung cancer patients and crizotinib efficacy in different lines. This national, non-interventional, multicenter, retrospective archive screening study evaluated demographic, clinical, and radiological imaging features, and treatment approaches in patients treated between 2013-2017. Totally 367 patients (54.8% males, median age at diagnosis 54 years) were included. Of them, 45.4% were smokers, and 8.7% had a family history of lung cancer. On radiological findings, 55.9% of the tumors were located peripherally, 7.7% of the patients had cavitary lesions, and 42.9% presented with pleural effusion. Pleural effusion was higher in nonsmokers than in smokers (37.3% vs. 25.3%, P = .018). About 47.4% of cases developed distant metastases during treatment, most frequently to the brain (26.2%). Chemotherapy was the first line treatment in 55.0%. Objective response rate was 61.9% (complete response: 7.6%; partial response: 54.2%). The highest complete and partial response rates were observed in patients who received crizotinib as the 2nd line treatment. The median progression-free survival was 14 months (standard error: 1.4, 95% confidence interval: 11.2–16.8 months). Crizotinib treatment lines yielded similar progression-free survival (P = .078). The most frequent treatment-related adverse event was fatigue (14.7%). Adrenal gland metastasis was significantly higher in males and smokers, and pleural involvement and effusion were significantly higher in nonsmokers—a novel finding that has not been reported previously. The radiological and histological characteristics were consistent with the literature data, but several differences in clinical characteristics might be related to population characteristics.

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Section: Discussionmentioning

confidence: 99%

A multicenter, retrospective archive study of radiological and clinical features of ALK-positive non-small cell lung cancer patients and crizotinib efficacy

Kilickap,

Ozturk,

Karadurmus

et al. 2024

Medicine

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“…In this study, we observed that a subset of patients had an extremely poor response to crizotinib (PFS <3 months) with poor survival (no longer than 6 months) compared with the literature. [2][3][4][5][6] Although they did not receive subsequent next-generation TKIs, their survival rate was worse than patients who only received crizotinib followed by chemotherapy, with a median survival of 20 months. 3 In the ALEX study, among patients who received crizotinib and alectinib, patients with early resistance to TKI had shorter survival (no longer than 12 months).…”

Section: Discussionmentioning

confidence: 99%

“…Anaplastic lymphoma kinase ( ALK )‑fusion genes represent a small but important part of oncogenic driver mutations in NSCLC, accounting for approximately 3%‑7% of all cases worldwide. 1 , 2 Small molecule tyrosine kinase inhibitors (TKIs) are the standard therapy for ALK -rearranged NSCLC. Crizotinib, a first-generation TKI, is the most widely used targeted drug to treat ALK -rearranged NSCLC.…”

Section: Introductionmentioning

confidence: 99%

High Tumor Mutation Burden and DNA Repair Gene Mutations are Associated with Primary Resistance to Crizotinib in ALK-Rearranged Lung Cancer

Xiao

Deng

et al. 2021

OTT

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Background About 20% of patients with ALK -rearranged non-small cell lung cancer (NSCLC) develop acquired resistance to tyrosine kinase inhibitor (TKI) during the first 6 months. This study aimed to examine the molecular mechanisms of early TKI resistance and prognosis in ALK -rearranged NSCLC. Methods Ten patients with ALK -rearranged NSCLC were included: five who developed rapid resistance to crizotinib (progression-free survival (PFS) ≤3 months) and five who exhibited a good response to crizotinib (PFS ≥36 months). The tumor specimens were subjected to whole-exome sequencing (WES). The validation cohort included 19 patients with ALK -rearranged NSCLC who received crizotinib; targeted sequencing of 43 selected genes was performed. The effect of the TP53 G245S mutation on crizotinib sensitivity was tested in H3122 cells. Results Mutations in DNA repair-associated genes were identified in primary resistance to crizotinib. Patients with a poor response to crizotinib harbored a greater burden of somatic mutations than those with a good response [median somatic mutations, 136 (range, 72–180) vs 31 (range, 10–48)]. Compared with the patients carrying wild-type TP53 or TP53 exon 3 deletion, 29 patients with TP53 G245S mutation showed a shorter survival time (P < 0.05), with a median PFS of 3 (95% CI: 1.9–4.1) months and a median overall survival of 7 (95% CI: 3.4–10.5) months. TP53 mutation promoted the proliferation of EML4-ALK -rearranged H3122 cells by approximately 3 folds (P < 0.001). H3122 cells with TP53 mutant were more sensitive to crizotinib compared with control cells. Conclusion A higher mutation burden and mutations in DNA repair gene, including TP53 , were potentially associated with primary resistance to crizotinib in ALK -rearranged NSCLC. An immune-checkpoint inhibition strategy could be examined, which might overcome primary resistance to crizotinib in ALK -rearranged NSCLC.

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“…[1][2][3] Approximately 3% to 5% of cases of NSCLC are histologically defined as anaplastic lymphoma kinase (ALK) positive (ALK1). 1,4,5 ALK1 NSCLCs are associated with advanced clinical stage at presentation and are more frequently observed in nonsmokers and younger patients compared with ALK-negative disease. 6 The current standard first-line treatment for patients with advanced ALK1 NSCLC is a firstor second-generation ALKtyrosine kinase inhibitor (TKI); nevertheless, many patients develop resistance to their initial and subsequent ALK-TKIs.…”

Section: Introductionmentioning

confidence: 99%

Matching-Adjusted Indirect Comparisons of Lorlatinib Versus Chemotherapy for Patients With Second-Line or Later Anaplastic Lymphoma Kinase–Positive Non–Small Cell Lung Cancer

Smith

Almeida²,

Inês³

et al. 2023

Value in Health

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Non-Small-Cell Lung Cancer (NSCLC) Harboring ALK Translocations: Clinical Characteristics and Management in a Real-Life Setting: a French Retrospective Analysis (GFPC 02–14 Study)

Abstract: The results of this real-life analysis suggest that the prognosis of NSCLC patients with theALK translocation may be better than that of the overall NSCLC population, but the outcomes were poorer than those of ALK+ NSCLC patients included in clinical studies.

Cited by 10 publications

References 24 publications

A multicenter, retrospective archive study of radiological and clinical features of ALK-positive non-small cell lung cancer patients and crizotinib efficacy

A multicenter, retrospective archive study of radiological and clinical features of ALK-positive non-small cell lung cancer patients and crizotinib efficacy

High Tumor Mutation Burden and DNA Repair Gene Mutations are Associated with Primary Resistance to Crizotinib in ALK-Rearranged Lung Cancer

Matching-Adjusted Indirect Comparisons of Lorlatinib Versus Chemotherapy for Patients With Second-Line or Later Anaplastic Lymphoma Kinase–Positive Non–Small Cell Lung Cancer

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