Treatment of advanced ALK-rearranged NSCLC following second-generation ALK–TKI failure

Fukuda, Akito; Yoshida, Tatsuya

doi:10.1080/14737140.2023.2265566

Cited by 6 publications

(6 citation statements)

References 99 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…If the resistance is caused by mutations such as G1202R , lorlatinib becomes the primary treatment option, leading to an mPFS of approximately 10 months ( 38 - 42 ). However, if the resistance occurs outside the kinase domain, chemotherapy is considered the best choice, resulting in an mPFS of around 3 months ( 18 , 43 ). According to some research findings, patients who switch to other next-generation ALK-TKI after resistance can achieve an mPFS of approximately 3 months ( 44 , 45 ).…”

Section: Discussionmentioning

confidence: 99%

Alectinib continuation beyond progression in ALK-positive non-small cell lung cancer with alectinib-refractory

Li,

Hao,

et al. 2024

Transl Lung Cancer Res

View full text Add to dashboard Cite

Background Alectinib, a next-generation anaplastic lymphoma kinase tyrosine kinase inhibitor (ALK-TKI), has demonstrated noteworthy efficacy in the treatment of non-small cell lung cancer (NSCLC). Unfortunately, 53.3% of untreated patients receiving first-line treatment with alectinib developed resistance to alectinib. However, despite the widespread use of alectinib, studies on the efficacy and safety of continuing alectinib with other necessary therapies after progression of alectinib and possible population of benefit are still limited. Methods This retrospective cohort study included fifteen patients with ALK -positive NSCLC from nine institutions in China who experienced disease progression after first- or second-line treatment and continued to receive alectinib treatment between 2019 and 2022. This study aimed to evaluate the median progression-free survival (mPFS), objective response rate (ORR), median overall survival (mOS), and adverse events (AEs) of continuing alectinib combined with other therapies after the emergence of drug resistance. Results Among fifteen patients eligible for this study, all patients started continuing treatment with alectinib after oligoprogression or central nervous system (CNS) progression. The mPFS for the whole cohort receiving continuing alectinib with other necessary therapies was 8 months [95% confidence interval (CI): 4 to not applicable (NA)], with an ORR of 46.7%. The mOS was not reached. During continuing alectinib treatment, only one patient experienced grade 2 elevation of aspartate aminotransferase (AST) and serum glutamic-oxaloacetic transaminase (SGOT). Conclusions The continuation of alectinib treatment combined with other necessary therapies demonstrates favorable response and safety in patients with ALK -positive NSCLC who experienced oligoprogression or CNS progression following alectinib in first- or second-line therapy. Instead of immediately switching to another ALK-TKI, continuing alectinib combined with other necessary therapies may offer greater survival benefits to the patients.

show abstract

Section: Discussionmentioning

confidence: 99%

Alectinib continuation beyond progression in ALK-positive non-small cell lung cancer with alectinib-refractory

Li,

Hao,

et al. 2024

Transl Lung Cancer Res

View full text Add to dashboard Cite

show abstract

“…Lorlatinib is the preferred option for patients with ALK mutations resistant to these TKIs, providing comprehensive coverage, including mutations such as G1202R and L1196M. For situations without specific resistance mutations, alternative options such as atezolizumab, bevacizumab, and platinum-based chemotherapy may be explored [161]. In cases of oligo-progression, the approach may involve maintaining the existing systemic treatment despite progression, accompanied by adding local therapies to address advancing lesions.…”

Section: Alk and Co-targeting Approachesmentioning

confidence: 99%

Unraveling the Potential of ALK-Targeted Therapies in Non-Small Cell Lung Cancer: Comprehensive Insights and Future Directions

Parvaresh,

Roozitalab,

Golandam

et al. 2024

Biomedicines

View full text Add to dashboard Cite

Background and Objective: This review comprehensively explores the intricate landscape of anaplastic lymphoma kinase (ALK), focusing specifically on its pivotal role in non-small cell lung cancer (NSCLC). Tracing ALK’s discovery, from its fusion with nucleolar phosphoprotein (NPM)-1 in anaplastic large cell non-Hodgkin’s lymphoma (ALCL) in 1994, the review elucidates the subsequent impact of ALK gene alterations in various malignancies, including inflammatory myofibroblastoma and NSCLC. Approximately 3–5% of NSCLC patients exhibit complex ALK rearrangements, leading to the approval of six ALK-tyrosine kinase inhibitors (TKIs) by 2022, revolutionizing the treatment landscape for advanced metastatic ALK + NSCLC. Notably, second-generation TKIs such as alectinib, ceritinib, and brigatinib have emerged to address resistance issues initially associated with the pioneer ALK-TKI, crizotinib. Methods: To ensure comprehensiveness, we extensively reviewed clinical trials on ALK inhibitors for NSCLC by 2023. Additionally, we systematically searched PubMed, prioritizing studies where the terms “ALK” AND “non-small cell lung cancer” AND/OR “NSCLC” featured prominently in the titles. This approach aimed to encompass a spectrum of relevant research studies, ensuring our review incorporates the latest and most pertinent information on innovative and alternative therapeutics for ALK + NSCLC. Key Content and Findings: Beyond exploring the intricate details of ALK structure and signaling, the review explores the convergence of ALK-targeted therapy and immunotherapy, investigating the potential of immune checkpoint inhibitors in ALK-altered NSCLC tumors. Despite encouraging preclinical data, challenges observed in trials assessing combinations such as nivolumab-crizotinib, mainly due to severe hepatic toxicity, emphasize the necessity for cautious exploration of these novel approaches. Additionally, the review explores innovative directions such as ALK molecular diagnostics, ALK vaccines, and biosensors, shedding light on their promising potential within ALK-driven cancers. Conclusions: This comprehensive analysis covers molecular mechanisms, therapeutic strategies, and immune interactions associated with ALK-rearranged NSCLC. As a pivotal resource, the review guides future research and therapeutic interventions in ALK-targeted therapy for NSCLC.

show abstract

“…How to select appropriate targeted drugs in patients previously treated with ALK inhibitors, however, has not been established. In fact, the National Comprehensive Cancer Network guidelines recommend that next generation ALK inhibitors can be directly used after ALK inhibitor failure regardless of determining the mechanism underlying drug resistance [ [1] , [2] , [3] ].…”

Section: Introductionmentioning

confidence: 99%

“…Previous studies have reported two major mechanisms of drug resistance in the treatment of advanced ALK -positive NSCLC failure to ALK inhibitors, as follows: ALK-dependent, such as ALK amplification and a secondary mutation of the ALK kinase domain; and ALK-independent, including bypass activation and phenotypic transformation [ [3] , [4] , [5] ]. Due to the relative low incidence of ALK -positive NSCLC and rare proportion of phenotypic transformation after ALK-tyrosine kinase inhibitor (TKI) resistance, there are no large clinical study reports that detail the clinical coping strategies and prognosis in this group of patients.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Changing ALK-TKI mechanisms of resistance in re-biopsies of ALK-rearranged NSCLC: ALK mutations followed by SCLC-like histologic transformation: A case report

He,

Yu,

Yan

et al. 2024

Heliyon

View full text Add to dashboard Cite

Treatment of advanced ALK-rearranged NSCLC following second-generation ALK–TKI failure

Cited by 6 publications

References 99 publications

Alectinib continuation beyond progression in ALK-positive non-small cell lung cancer with alectinib-refractory

Alectinib continuation beyond progression in ALK-positive non-small cell lung cancer with alectinib-refractory

Unraveling the Potential of ALK-Targeted Therapies in Non-Small Cell Lung Cancer: Comprehensive Insights and Future Directions

Changing ALK-TKI mechanisms of resistance in re-biopsies of ALK-rearranged NSCLC: ALK mutations followed by SCLC-like histologic transformation: A case report

Contact Info

Product

Resources

About