Final progression-free survival results from the J-ALEX study of alectinib versus crizotinib in ALK-positive non-small-cell lung cancer

Nakagawa, Kazuhiko; Hida, Toyoaki; Nokihara, Hiroshi; Morise, Masahiro; Azuma, Koichi; Kim, Young Hak; Seto, Takashi; Takiguchi, Yuichi; Nishio, Makoto; Yoshioka, Hiroshige; Kumagai, Toru; Hotta, Katsuyuki; Watanabe, Satoshi; Goto, Kōichi; Satouchi, Miyako; Kozuki, Toshiyuki; Koyama, Ryo; Mitsudomi, Tetsuya; Yamamoto, Nobuyuki; Asakawa, T.; Hayashi, Motoya; Hasegawa, Wakako; Tamura, Tomohide

doi:10.1016/j.lungcan.2019.11.025

Cited by 113 publications

(89 citation statements)

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“…This finding may be explained by the fact that, irrespective of treatment regimens, patients included in this study possessed (by chance) rapidly progressing tumors; the duration of prior treatment with alectinib among patients in our series was shorter than that of other reports (median, 6.7 [range: 12.4–34.1] months) (Table 6). 5 The reason why the patients enrolled in the study had rapidly progressing tumors may be due to the fact that this study was started immediately after the approval of alectinib as first‐line therapy, and therefore many patients with early alectinib resistance were enrolled. Regarding the safety profile, although AEs resulted in treatment discontinuation in one patient (11%), these complications were temporary and manageable with supportive care.…”

Section: Discussionmentioning

confidence: 99%

“…Subsequently, other ALK‐TKIs have been introduced into clinical practice. Among them, alectinib, a relatively potent and selective ALK‐TKI, is associated with substantial improvement in patient survival compared to that observed with crizotinib 5,6 . In fact, the National Comprehensive Cancer Network guidelines 7 now recommend alectinib as first‐line ALK‐TKI monotherapy for ALK ‐rearranged advanced NSCLC.…”

Section: Introductionmentioning

confidence: 99%

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Crizotinib for recurring non‐small‐cell lung cancer with EML4‐ALK fusion genes previously treated with alectinib: A phase II trial

et al. 2021

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Background The efficacy of crizotinib treatment for recurring EML4‐ALK‐positive non‐small cell lung cancer (NSCLC) previously treated with alectinib is unclear. Based on our preclinical findings regarding hepatocyte growth factor/mesenchymal epithelial transition (MET) pathway activation as a potential mechanism of acquired resistance to alectinib, we conducted a phase II trial of the anaplastic lymphoma kinase/MET inhibitor, crizotinib, in patients with alectinib‐refractory, EML4‐ALK‐positive NSCLC. Methods Patients with ALK‐rearranged tumors treated with alectinib immediately before enrolling in the trial received crizotinib monotherapy. The objective response rate was the primary outcome of interest. Results Nine (100%) patients achieved a partial response with alectinib therapy with a median treatment duration of 6.7 months. Crizotinib was administered with a median treatment interval of 50 (range, 20–433) days. The overall response rate was 33.3% (90% confidence interval [CI]: 9.8–65.5 and 95% CI: 7.5–70.1), which did not reach the predefined criteria of 50%. Two (22%) patients who achieved a partial response had brain metastases at baseline. Progression‐free survival (median, 2.2 months) was not affected by the duration of treatment with alectinib. The median survival time was 24.1 months. The most common adverse events were an increased aspartate transaminase/alanine transaminase (AST/ALT) ratio (44%) and appetite loss (33%); one patient developed transient grade 4 AST/ALT elevation, resulting in treatment discontinuation. Other adverse events were consistent with those previously reported; no treatment‐related deaths occurred. Conclusions Although the desired response rate was not achieved, crizotinib monotherapy following treatment with alectinib showed efficacy alongside previously described adverse events.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Crizotinib for recurring non‐small‐cell lung cancer with EML4‐ALK fusion genes previously treated with alectinib: A phase II trial

et al. 2021

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“…Three randomized, controlled clinical trials (ALEX, ALESIA and J-ALEX) with a total of 7 articles and 697 patients (317 patients in the crizotinib arm and 380 patients in the alectinib arm) were included for the nal analysis [11][12][13][14][22][23][24] (Fig. 1).…”

Section: Search Resultsmentioning

confidence: 99%

Crizotinib versus alectinib for treatment of ALK-positive non-small cell lung cancer: a pooled analysis of the ALEX, ALESIA and J-ALEX clinical trials

Zeng¹,

Zhang²,

He³

et al. 2020

Preprint

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Background: Crizotinib and alectinib were the two most commonly used anaplastic lymphoma kinase (ALK) inhibitors for ALK-positive non-small cell lung cancer (NSCLC). We compared their antitumor efficacies and adverse effects based on a pooled analysis of the ALEX, ALESIA and J-ALEX clinical trials.Methods: Seven databases were searched for eligible articles. The primary endpoints included overall survival (OS), progression-free survival (PFS), central nervous system (CNS)-PFS, drug responses and adverse effects (AEs).Results: Three randomized controlled clinical trials (ALEX, ALESIA and J-ALEX) with a total of 7 articles and 697 patients were included. Compared with crizotinib, alectinib exhibited superior efficacy in PFS (HR [hazard ratio]: 0.35, [0.25-0.49], p < 0.00001), OS (HR: 0.66, [0.47-0.92], p = 0.02), CNS-PFS (HR: 0.17, [0.11-0.24], p < 0.00001), duration of response (HR: 0.31, [0.23-0.42], p < 0.00001), objective response rate (ORR) (Risk ratio [RR]: 0.87, [0.80-0.94], p = 0.0003), partial response (PR) (RR: 0.88, [0.81-0.96], p = 0.004), and grade 3-5 AEs (RR: 1.43, [1.09-1.87], p = 0.009). Additionally, the survival advantages of alectinib compared with crizotinib increased with alectinib’s prolongation of survival time. The disease control rate, complete response and total AEs were comparable between the two groups. A greater increase in constipation, nausea, diarrhea, alanine aminotransferase, vomiting, aspartate aminotransferase, peripheral edema, dysgeusia, and visual impairment as well as a greater decrease in appetite and neutrophil count were associated with the crizotinib groupConclusions: In both antitumor efficacy and safety, alectinib appears to be superior to crizotinib for the treatment of ALK-positive NSCLC.

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“…Our cohort included only ALK-positive patients with BM that received ALK-TKI in the first-line (patients diagnosed between 2011 and 2019); most of the patients also received second-generation TKIs [ 14 , 25 , 26 , 27 , 28 ], which is considered the standard treatment today. Second-generation ALK TKIs have better intracranial activity, especially alectinib [ 12 , 29 ] and brigatinib [ 30 ], when used in a first-line setting.…”

Section: Discussionmentioning

confidence: 99%

ALK-Brain Prognostic Index—Preliminary Study of a Prognostic Tool for Patients with ALK-Rearranged, Non-small Cell Lung Cancer and Brain Metastases

Tsakonas

Kamali

Petris

et al. 2020

Cancers

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Background: Disease-specific Graded Prognostic Assessment (DS-GPA) is the most validated prognostic tool for patients with brain metastasized lung cancer. The Lung-molGPA scoring system was recently introduced for oncogenic-driven brain metastasized lung cancer, but has not yet been validated in cohorts including only ALK-translocated tumors. Methods: We designed a retrospective cohort study consisting of 44 patients with brain metastasized ALK-positive, non-small cell lung cancer (NSCLC) who were treated between January 2009 and November 2019 at Karolinska University Hospital in Stockholm, Sweden. Information about demographics and clinicopathological parameters were collected. Predictors of overall survival (OS) were identified by Cox regression analyses. A bootstrap validation with 1000 samples was performed in order to compare the different prognostic scores. Results: The variables found to independently influence OS in the multivariate analysis, i.e., PS, sex and brain metastases at diagnosis, were used as prognostic variables in our new prognostic index (ALK-BPI). Patients were divided into two prognostic groups. The median OS was 65.7 months for the good prognostic group and 22.7 months for the poor prognostic group (p = 0.0068). In the univariate analysis of the different prognostic scores, ALK-BPI performed better than the others (HR = 3.6; 95% CI: 1.3–9.9). The mean C-statistics of the different prognostic scores were compared to each other, and no significant difference was observed. Conclusion: We propose the ALK-BPI score as a new prognostic tool that can easily be applied for ALK-positive lung cancer patients with brain metastases in daily clinical practice, as it has at least the same prognostic value as Lung-molGPA.

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Final progression-free survival results from the J-ALEX study of alectinib versus crizotinib in ALK-positive non-small-cell lung cancer

Cited by 113 publications

References 8 publications

Crizotinib for recurring non‐small‐cell lung cancer with EML4‐ALK fusion genes previously treated with alectinib: A phase II trial

Crizotinib for recurring non‐small‐cell lung cancer with EML4‐ALK fusion genes previously treated with alectinib: A phase II trial

Crizotinib versus alectinib for treatment of ALK-positive non-small cell lung cancer: a pooled analysis of the ALEX, ALESIA and J-ALEX clinical trials

ALK-Brain Prognostic Index—Preliminary Study of a Prognostic Tool for Patients with ALK-Rearranged, Non-small Cell Lung Cancer and Brain Metastases

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