Three-year follow-up of an alectinib phase I/II study in ALK-positive non–small-cell lung cancer

AF-001JP

Tomohide Tamura, Katsuyuki Kiura, Takashi Seto, Kazuhiko Nakagawa, Makoto Maemondo, Akira Inoue, Toyoaki Hida, Hiroshige Yoshioka, Masao Harada, Yuichiro Ohe, Naoyuki Nogami, Haruyasu Murakami, Hiroshi Kuriki, Tadashi Shimada, Tomohiro Tanaka, Kengo Takeuchi, Makoto Nishio

Research output: Contribution to journalArticle

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Abstract

Purpose Alectinib is an anaplastic lymphoma kinase (ALK) –specific kinase inhibitor that seems to be effective against non–small-cell lung cancer (NSCLC) with a variety of ALK mutations. The primary analysis of AF-001JP reported a promising overall response rate. To assess progression-free survival (PFS) and overall survival (OS), patients from the phase II part of AF-001JP were followed up for approximately 3 years. Patients and Methods Oral alectinib 300 mg was administered twice per day to patients with ALK inhibitor–naïve, ALK-positive NSCLC who had progressed after one or more regimens of previous chemotherapy. In this long-term follow-up, efficacy (PFS, OS), correlation between tumor shrinkage and PFS, safety of alectinib, and relief of cancer symptoms were evaluated. Results At the updated data cutoff (September 10, 2015; first patient in August 30, 2011, last patient in April 18, 2012), 25 of 46 phase II patients were still receiving alectinib. Disease progression was confirmed in 18 patients (39%); median PFS was not reached (3-year PFS rate, 62%; 95% CI, 45 to 75). Fourteen patients had brain metastases at baseline; of these, 6 remained in the study without CNS and systemic progression. Tumor shrinkage and PFS showed no correlation. The 3-year OS rate was 78% (13 events). The most common treatment-related adverse event (all grades) was increased blood bilirubin (36.2%). Most cancer symptoms were relieved early, and medication for symptoms was dramatically decreased during alectinib therapy. Conclusion Alectinib was effective in this 3-year follow-up with a favorable safety profile over a long administration period in ALK-positive NSCLC without previous ALK inhibitor treatment.

Original languageEnglish
Pages (from-to)1515-1521
Number of pages7
JournalJournal of Clinical Oncology
Volume35
Issue number14
DOIs
Publication statusPublished - May 10 2017

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Non-Small Cell Lung Carcinoma
Disease-Free Survival
Neoplasms
Survival Rate
Safety
Survival
CH5424802
anaplastic lymphoma kinase
Bilirubin
Disease Progression
Phosphotransferases
Therapeutics
Neoplasm Metastasis
Drug Therapy
Mutation
Brain

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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Three-year follow-up of an alectinib phase I/II study in ALK-positive non–small-cell lung cancer : AF-001JP. / Tamura, Tomohide; Kiura, Katsuyuki; Seto, Takashi; Nakagawa, Kazuhiko; Maemondo, Makoto; Inoue, Akira; Hida, Toyoaki; Yoshioka, Hiroshige; Harada, Masao; Ohe, Yuichiro; Nogami, Naoyuki; Murakami, Haruyasu; Kuriki, Hiroshi; Shimada, Tadashi; Tanaka, Tomohiro; Takeuchi, Kengo; Nishio, Makoto.

In: Journal of Clinical Oncology, Vol. 35, No. 14, 10.05.2017, p. 1515-1521.

Research output: Contribution to journalArticle

Tamura, T, Kiura, K, Seto, T, Nakagawa, K, Maemondo, M, Inoue, A, Hida, T, Yoshioka, H, Harada, M, Ohe, Y, Nogami, N, Murakami, H, Kuriki, H, Shimada, T, Tanaka, T, Takeuchi, K & Nishio, M 2017, 'Three-year follow-up of an alectinib phase I/II study in ALK-positive non–small-cell lung cancer: AF-001JP', Journal of Clinical Oncology, vol. 35, no. 14, pp. 1515-1521. https://doi.org/10.1200/JCO.2016.70.5749
Tamura, Tomohide ; Kiura, Katsuyuki ; Seto, Takashi ; Nakagawa, Kazuhiko ; Maemondo, Makoto ; Inoue, Akira ; Hida, Toyoaki ; Yoshioka, Hiroshige ; Harada, Masao ; Ohe, Yuichiro ; Nogami, Naoyuki ; Murakami, Haruyasu ; Kuriki, Hiroshi ; Shimada, Tadashi ; Tanaka, Tomohiro ; Takeuchi, Kengo ; Nishio, Makoto. / Three-year follow-up of an alectinib phase I/II study in ALK-positive non–small-cell lung cancer : AF-001JP. In: Journal of Clinical Oncology. 2017 ; Vol. 35, No. 14. pp. 1515-1521.
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abstract = "Purpose Alectinib is an anaplastic lymphoma kinase (ALK) –specific kinase inhibitor that seems to be effective against non–small-cell lung cancer (NSCLC) with a variety of ALK mutations. The primary analysis of AF-001JP reported a promising overall response rate. To assess progression-free survival (PFS) and overall survival (OS), patients from the phase II part of AF-001JP were followed up for approximately 3 years. Patients and Methods Oral alectinib 300 mg was administered twice per day to patients with ALK inhibitor–na{\"i}ve, ALK-positive NSCLC who had progressed after one or more regimens of previous chemotherapy. In this long-term follow-up, efficacy (PFS, OS), correlation between tumor shrinkage and PFS, safety of alectinib, and relief of cancer symptoms were evaluated. Results At the updated data cutoff (September 10, 2015; first patient in August 30, 2011, last patient in April 18, 2012), 25 of 46 phase II patients were still receiving alectinib. Disease progression was confirmed in 18 patients (39{\%}); median PFS was not reached (3-year PFS rate, 62{\%}; 95{\%} CI, 45 to 75). Fourteen patients had brain metastases at baseline; of these, 6 remained in the study without CNS and systemic progression. Tumor shrinkage and PFS showed no correlation. The 3-year OS rate was 78{\%} (13 events). The most common treatment-related adverse event (all grades) was increased blood bilirubin (36.2{\%}). Most cancer symptoms were relieved early, and medication for symptoms was dramatically decreased during alectinib therapy. Conclusion Alectinib was effective in this 3-year follow-up with a favorable safety profile over a long administration period in ALK-positive NSCLC without previous ALK inhibitor treatment.",
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T1 - Three-year follow-up of an alectinib phase I/II study in ALK-positive non–small-cell lung cancer

T2 - AF-001JP

AU - Tamura, Tomohide

AU - Kiura, Katsuyuki

AU - Seto, Takashi

AU - Nakagawa, Kazuhiko

AU - Maemondo, Makoto

AU - Inoue, Akira

AU - Hida, Toyoaki

AU - Yoshioka, Hiroshige

AU - Harada, Masao

AU - Ohe, Yuichiro

AU - Nogami, Naoyuki

AU - Murakami, Haruyasu

AU - Kuriki, Hiroshi

AU - Shimada, Tadashi

AU - Tanaka, Tomohiro

AU - Takeuchi, Kengo

AU - Nishio, Makoto

PY - 2017/5/10

Y1 - 2017/5/10

N2 - Purpose Alectinib is an anaplastic lymphoma kinase (ALK) –specific kinase inhibitor that seems to be effective against non–small-cell lung cancer (NSCLC) with a variety of ALK mutations. The primary analysis of AF-001JP reported a promising overall response rate. To assess progression-free survival (PFS) and overall survival (OS), patients from the phase II part of AF-001JP were followed up for approximately 3 years. Patients and Methods Oral alectinib 300 mg was administered twice per day to patients with ALK inhibitor–naïve, ALK-positive NSCLC who had progressed after one or more regimens of previous chemotherapy. In this long-term follow-up, efficacy (PFS, OS), correlation between tumor shrinkage and PFS, safety of alectinib, and relief of cancer symptoms were evaluated. Results At the updated data cutoff (September 10, 2015; first patient in August 30, 2011, last patient in April 18, 2012), 25 of 46 phase II patients were still receiving alectinib. Disease progression was confirmed in 18 patients (39%); median PFS was not reached (3-year PFS rate, 62%; 95% CI, 45 to 75). Fourteen patients had brain metastases at baseline; of these, 6 remained in the study without CNS and systemic progression. Tumor shrinkage and PFS showed no correlation. The 3-year OS rate was 78% (13 events). The most common treatment-related adverse event (all grades) was increased blood bilirubin (36.2%). Most cancer symptoms were relieved early, and medication for symptoms was dramatically decreased during alectinib therapy. Conclusion Alectinib was effective in this 3-year follow-up with a favorable safety profile over a long administration period in ALK-positive NSCLC without previous ALK inhibitor treatment.

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