Protocol Design for the Bench to Bed Trial in Alectinib-Refractory Non–Small-Cell Lung Cancer Patients Harboring the EML4-ALK Fusion Gene (ALRIGHT/OLCSG1405)

Isozaki, Hideko; Hotta, Katsuyuki; Ichihara, Eiki; Takigawa, Nagio; Ohashi, Kadoaki; Kubo, Toshio; Ninomiya, Takashi; Ninomiya, Kiichiro; Oda, Naohiro; Yoshioka, Hiroshige; Ichikawa, Hirohisa; Inoue, Masatoshi; Takata, Ichiro; Shibayama, Takuo; Kuyama, Shoichi; Sugimoto, Keisuke; Harada, Daijiro; Harita, Shingo; Sendo, Toshiaki; Tanimoto, Mitsune; Kiura, Katsuyuki

doi:10.1016/j.cllc.2016.05.005

Cited by 10 publications

(4 citation statements)

References 15 publications

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“…Treatment interruption or dose modification was allowed if clinically justified. The protocol summary, including participant and intervention details, has been previously described 1 . Written informed consent was obtained from all patients prior to screening.…”

Section: Methodsmentioning

confidence: 99%

“…The discovery of echinoderm microtubule‐associated protein‐like 4 ( EML4 )‐anaplastic lymphoma kinase ( ALK ) fusion driver oncogenes has led to an evolution in treatment for advanced non‐small‐cell lung cancer (NSCLC) 1 and epidermal growth factor receptor ( EGFR )‐mutant tumors 2 . Crizotinib, the first ALK‐tyrosine kinase inhibitor (TKI), has been associated with a significant survival advantage compared to standard cytotoxic chemotherapy in randomized trials 3,4 .…”

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: Methodsmentioning

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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“…However, C1156Y/T, I1151Tins and L1152P/R mutations have been associated with the emergence of ceritinib resistance (19). Alectinib has a better efficacy against G1269A, L1196M, F1174L and C1156Y mutations (20); however, alectinib treatment has been shown to cause the emergence of resistance mutations (I1171T/N/S, V1180L and G1202R) (14,58), and the activated bypass signaling pathway to be mediated by hepatocyte growth factor (HGF) and MET (59). Epithelial-mesenchymal transition (EMT) is a potential mechanism of alectinib resistance, characterized by the loss of E-cadherin and increased expression of waveform proteins (60).…”

Section: Mechanisms Of Alk Inhibitor Resistancementioning

confidence: 99%

Role of STK11 in ALK‑positive non‑small cell lung cancer (Review)

Zhou

Yan

et al. 2022

Oncol Lett

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Anaplastic lymphoma kinase (ALK) inhibitors have been shown to be effective in treating patients with ALK-positive non-small cell lung cancer (NSCLC), and crizotinib, ceritinib and alectinib have been approved as clinical first-line therapeutic agents. The availability of these inhibitors has also largely changed the treatment strategy for advanced ALK-positive NSCLC. However, patients still inevitably develop resistance to ALK inhibitors, leading to tumor recurrence or metastasis. The most critical issues that need to be addressed in the current treatment of ALK-positive NSCLC include the high cost of targeted inhibitors and the potential for increased toxicity and resistance to combination therapy. Recently, it has been suggested that the serine/threonine kinase 11 (STK11) mutation may serve as one of the biomarkers for immunotherapy in NSCLC. Therefore, the main purpose of this review was to summarize the role of STK11 in ALK-positive NSCLC. The present review also summarizes the treatment and drug resistance studies in ALK-positive NSCLC and the current status of STK11 research in NSCLC.

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“…4,5 Although kinase inhibitors (targeting epidermal growth factor receptor, anaplastic lymphoma kinase and c-ros oncogene 1) and immune checkpoint inhibitors (anti-programmed cell death 1 antibodies, anti-programmed cell death ligand 1 antibodies, atezolizumab and durvalumab) have been widely used in clinical practices according to the aberrant status of the cancer, it still a quite limited number of LUSC cases that were actually suitable and efficient for these treatment strategies. [6][7][8][9][10] It is still an urgent requirement to investigate the denite molecular mechanism and antitumor treatment strategies of LUSC. 11,12 Therefore, identication of the difference between tumor tissues and adjacent tissues is very meaningful for contributing to the molecular mechanism research.…”

Section: Introductionmentioning

confidence: 99%

Increased expression of core-fucosylated glycans in human lung squamous cell carcinoma

Wang

Jia

et al. 2019

RSC Adv.

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Protocol Design for the Bench to Bed Trial in Alectinib-Refractory Non–Small-Cell Lung Cancer Patients Harboring the EML4-ALK Fusion Gene (ALRIGHT/OLCSG1405)

Cited by 10 publications

References 15 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

Role of STK11 in ALK‑positive non‑small cell lung cancer (Review)

Increased expression of core-fucosylated glycans in human lung squamous cell carcinoma

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