title: Three-Year Follow-Up of an Alectinib Phase I/II Study in ALK-Positive Non-Small-Cell Lung Cancer: AF-001JP.
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.
authors.affiliation: Tomohide Tamura, St Luke's International Hospital; Yuichiro Ohe, National Cancer Center Hospital; Hiroshi Kuriki, Tadashi Shimada, and Tomohiro Tanaka, Chugai Pharmaceutical; Kengo Takeuchi, Japanese Foundation for Cancer Research; Makoto Nishio, The Cancer Institute Hospital of the Japanese Foundation for Cancer Research, Tokyo; Katsuyuki Kiura, Okayama University Hospital, Okayama; Takashi Seto, National Kyusyu Cancer Center, Fukuoka; Kazuhiko Nakagawa, Kindai University, Osaka-Sayama; Makoto Maemondo, Miyagi Cancer Center, Natori; Akira Inoue, Tohoku University, Sendai; Toyoaki Hida, Aichi Cancer Center, Nagoya; Hiroshige Yoshioka, Kurashiki Central Hospital, Kurashiki; Masao Harada, Hokkaido Cancer Center, Sapporo; Naoyuki Nogami, National Hospital Organization Shikoku Cancer Center, Matsuyama; and Haruyasu Murakami, Shizuoka Cancer Center, Shizuoka, Japan.
authors.forename: Tomohide
authors.initials: T
authors.lastname: Tamura
authors.affiliation: Tomohide Tamura, St Luke's International Hospital; Yuichiro Ohe, National Cancer Center Hospital; Hiroshi Kuriki, Tadashi Shimada, and Tomohiro Tanaka, Chugai Pharmaceutical; Kengo Takeuchi, Japanese Foundation for Cancer Research; Makoto Nishio, The Cancer Institute Hospital of the Japanese Foundation for Cancer Research, Tokyo; Katsuyuki Kiura, Okayama University Hospital, Okayama; Takashi Seto, National Kyusyu Cancer Center, Fukuoka; Kazuhiko Nakagawa, Kindai University, Osaka-Sayama; Makoto Maemondo, Miyagi Cancer Center, Natori; Akira Inoue, Tohoku University, Sendai; Toyoaki Hida, Aichi Cancer Center, Nagoya; Hiroshige Yoshioka, Kurashiki Central Hospital, Kurashiki; Masao Harada, Hokkaido Cancer Center, Sapporo; Naoyuki Nogami, National Hospital Organization Shikoku Cancer Center, Matsuyama; and Haruyasu Murakami, Shizuoka Cancer Center, Shizuoka, Japan.
authors.forename: Katsuyuki
authors.initials: K
authors.lastname: Kiura
authors.affiliation: Tomohide Tamura, St Luke's International Hospital; Yuichiro Ohe, National Cancer Center Hospital; Hiroshi Kuriki, Tadashi Shimada, and Tomohiro Tanaka, Chugai Pharmaceutical; Kengo Takeuchi, Japanese Foundation for Cancer Research; Makoto Nishio, The Cancer Institute Hospital of the Japanese Foundation for Cancer Research, Tokyo; Katsuyuki Kiura, Okayama University Hospital, Okayama; Takashi Seto, National Kyusyu Cancer Center, Fukuoka; Kazuhiko Nakagawa, Kindai University, Osaka-Sayama; Makoto Maemondo, Miyagi Cancer Center, Natori; Akira Inoue, Tohoku University, Sendai; Toyoaki Hida, Aichi Cancer Center, Nagoya; Hiroshige Yoshioka, Kurashiki Central Hospital, Kurashiki; Masao Harada, Hokkaido Cancer Center, Sapporo; Naoyuki Nogami, National Hospital Organization Shikoku Cancer Center, Matsuyama; and Haruyasu Murakami, Shizuoka Cancer Center, Shizuoka, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Seto
authors.affiliation: Tomohide Tamura, St Luke's International Hospital; Yuichiro Ohe, National Cancer Center Hospital; Hiroshi Kuriki, Tadashi Shimada, and Tomohiro Tanaka, Chugai Pharmaceutical; Kengo Takeuchi, Japanese Foundation for Cancer Research; Makoto Nishio, The Cancer Institute Hospital of the Japanese Foundation for Cancer Research, Tokyo; Katsuyuki Kiura, Okayama University Hospital, Okayama; Takashi Seto, National Kyusyu Cancer Center, Fukuoka; Kazuhiko Nakagawa, Kindai University, Osaka-Sayama; Makoto Maemondo, Miyagi Cancer Center, Natori; Akira Inoue, Tohoku University, Sendai; Toyoaki Hida, Aichi Cancer Center, Nagoya; Hiroshige Yoshioka, Kurashiki Central Hospital, Kurashiki; Masao Harada, Hokkaido Cancer Center, Sapporo; Naoyuki Nogami, National Hospital Organization Shikoku Cancer Center, Matsuyama; and Haruyasu Murakami, Shizuoka Cancer Center, Shizuoka, Japan.
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Nakagawa
authors.affiliation: Tomohide Tamura, St Luke's International Hospital; Yuichiro Ohe, National Cancer Center Hospital; Hiroshi Kuriki, Tadashi Shimada, and Tomohiro Tanaka, Chugai Pharmaceutical; Kengo Takeuchi, Japanese Foundation for Cancer Research; Makoto Nishio, The Cancer Institute Hospital of the Japanese Foundation for Cancer Research, Tokyo; Katsuyuki Kiura, Okayama University Hospital, Okayama; Takashi Seto, National Kyusyu Cancer Center, Fukuoka; Kazuhiko Nakagawa, Kindai University, Osaka-Sayama; Makoto Maemondo, Miyagi Cancer Center, Natori; Akira Inoue, Tohoku University, Sendai; Toyoaki Hida, Aichi Cancer Center, Nagoya; Hiroshige Yoshioka, Kurashiki Central Hospital, Kurashiki; Masao Harada, Hokkaido Cancer Center, Sapporo; Naoyuki Nogami, National Hospital Organization Shikoku Cancer Center, Matsuyama; and Haruyasu Murakami, Shizuoka Cancer Center, Shizuoka, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Maemondo
authors.affiliation: Tomohide Tamura, St Luke's International Hospital; Yuichiro Ohe, National Cancer Center Hospital; Hiroshi Kuriki, Tadashi Shimada, and Tomohiro Tanaka, Chugai Pharmaceutical; Kengo Takeuchi, Japanese Foundation for Cancer Research; Makoto Nishio, The Cancer Institute Hospital of the Japanese Foundation for Cancer Research, Tokyo; Katsuyuki Kiura, Okayama University Hospital, Okayama; Takashi Seto, National Kyusyu Cancer Center, Fukuoka; Kazuhiko Nakagawa, Kindai University, Osaka-Sayama; Makoto Maemondo, Miyagi Cancer Center, Natori; Akira Inoue, Tohoku University, Sendai; Toyoaki Hida, Aichi Cancer Center, Nagoya; Hiroshige Yoshioka, Kurashiki Central Hospital, Kurashiki; Masao Harada, Hokkaido Cancer Center, Sapporo; Naoyuki Nogami, National Hospital Organization Shikoku Cancer Center, Matsuyama; and Haruyasu Murakami, Shizuoka Cancer Center, Shizuoka, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Inoue
authors.affiliation: Tomohide Tamura, St Luke's International Hospital; Yuichiro Ohe, National Cancer Center Hospital; Hiroshi Kuriki, Tadashi Shimada, and Tomohiro Tanaka, Chugai Pharmaceutical; Kengo Takeuchi, Japanese Foundation for Cancer Research; Makoto Nishio, The Cancer Institute Hospital of the Japanese Foundation for Cancer Research, Tokyo; Katsuyuki Kiura, Okayama University Hospital, Okayama; Takashi Seto, National Kyusyu Cancer Center, Fukuoka; Kazuhiko Nakagawa, Kindai University, Osaka-Sayama; Makoto Maemondo, Miyagi Cancer Center, Natori; Akira Inoue, Tohoku University, Sendai; Toyoaki Hida, Aichi Cancer Center, Nagoya; Hiroshige Yoshioka, Kurashiki Central Hospital, Kurashiki; Masao Harada, Hokkaido Cancer Center, Sapporo; Naoyuki Nogami, National Hospital Organization Shikoku Cancer Center, Matsuyama; and Haruyasu Murakami, Shizuoka Cancer Center, Shizuoka, Japan.
authors.forename: Toyoaki
authors.initials: T
authors.lastname: Hida
authors.affiliation: Tomohide Tamura, St Luke's International Hospital; Yuichiro Ohe, National Cancer Center Hospital; Hiroshi Kuriki, Tadashi Shimada, and Tomohiro Tanaka, Chugai Pharmaceutical; Kengo Takeuchi, Japanese Foundation for Cancer Research; Makoto Nishio, The Cancer Institute Hospital of the Japanese Foundation for Cancer Research, Tokyo; Katsuyuki Kiura, Okayama University Hospital, Okayama; Takashi Seto, National Kyusyu Cancer Center, Fukuoka; Kazuhiko Nakagawa, Kindai University, Osaka-Sayama; Makoto Maemondo, Miyagi Cancer Center, Natori; Akira Inoue, Tohoku University, Sendai; Toyoaki Hida, Aichi Cancer Center, Nagoya; Hiroshige Yoshioka, Kurashiki Central Hospital, Kurashiki; Masao Harada, Hokkaido Cancer Center, Sapporo; Naoyuki Nogami, National Hospital Organization Shikoku Cancer Center, Matsuyama; and Haruyasu Murakami, Shizuoka Cancer Center, Shizuoka, Japan.
authors.forename: Hiroshige
authors.initials: H
authors.lastname: Yoshioka
authors.affiliation: Tomohide Tamura, St Luke's International Hospital; Yuichiro Ohe, National Cancer Center Hospital; Hiroshi Kuriki, Tadashi Shimada, and Tomohiro Tanaka, Chugai Pharmaceutical; Kengo Takeuchi, Japanese Foundation for Cancer Research; Makoto Nishio, The Cancer Institute Hospital of the Japanese Foundation for Cancer Research, Tokyo; Katsuyuki Kiura, Okayama University Hospital, Okayama; Takashi Seto, National Kyusyu Cancer Center, Fukuoka; Kazuhiko Nakagawa, Kindai University, Osaka-Sayama; Makoto Maemondo, Miyagi Cancer Center, Natori; Akira Inoue, Tohoku University, Sendai; Toyoaki Hida, Aichi Cancer Center, Nagoya; Hiroshige Yoshioka, Kurashiki Central Hospital, Kurashiki; Masao Harada, Hokkaido Cancer Center, Sapporo; Naoyuki Nogami, National Hospital Organization Shikoku Cancer Center, Matsuyama; and Haruyasu Murakami, Shizuoka Cancer Center, Shizuoka, Japan.
authors.forename: Masao
authors.initials: M
authors.lastname: Harada
authors.affiliation: Tomohide Tamura, St Luke's International Hospital; Yuichiro Ohe, National Cancer Center Hospital; Hiroshi Kuriki, Tadashi Shimada, and Tomohiro Tanaka, Chugai Pharmaceutical; Kengo Takeuchi, Japanese Foundation for Cancer Research; Makoto Nishio, The Cancer Institute Hospital of the Japanese Foundation for Cancer Research, Tokyo; Katsuyuki Kiura, Okayama University Hospital, Okayama; Takashi Seto, National Kyusyu Cancer Center, Fukuoka; Kazuhiko Nakagawa, Kindai University, Osaka-Sayama; Makoto Maemondo, Miyagi Cancer Center, Natori; Akira Inoue, Tohoku University, Sendai; Toyoaki Hida, Aichi Cancer Center, Nagoya; Hiroshige Yoshioka, Kurashiki Central Hospital, Kurashiki; Masao Harada, Hokkaido Cancer Center, Sapporo; Naoyuki Nogami, National Hospital Organization Shikoku Cancer Center, Matsuyama; and Haruyasu Murakami, Shizuoka Cancer Center, Shizuoka, Japan.
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Ohe
authors.affiliation: Tomohide Tamura, St Luke's International Hospital; Yuichiro Ohe, National Cancer Center Hospital; Hiroshi Kuriki, Tadashi Shimada, and Tomohiro Tanaka, Chugai Pharmaceutical; Kengo Takeuchi, Japanese Foundation for Cancer Research; Makoto Nishio, The Cancer Institute Hospital of the Japanese Foundation for Cancer Research, Tokyo; Katsuyuki Kiura, Okayama University Hospital, Okayama; Takashi Seto, National Kyusyu Cancer Center, Fukuoka; Kazuhiko Nakagawa, Kindai University, Osaka-Sayama; Makoto Maemondo, Miyagi Cancer Center, Natori; Akira Inoue, Tohoku University, Sendai; Toyoaki Hida, Aichi Cancer Center, Nagoya; Hiroshige Yoshioka, Kurashiki Central Hospital, Kurashiki; Masao Harada, Hokkaido Cancer Center, Sapporo; Naoyuki Nogami, National Hospital Organization Shikoku Cancer Center, Matsuyama; and Haruyasu Murakami, Shizuoka Cancer Center, Shizuoka, Japan.
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Nogami
authors.affiliation: Tomohide Tamura, St Luke's International Hospital; Yuichiro Ohe, National Cancer Center Hospital; Hiroshi Kuriki, Tadashi Shimada, and Tomohiro Tanaka, Chugai Pharmaceutical; Kengo Takeuchi, Japanese Foundation for Cancer Research; Makoto Nishio, The Cancer Institute Hospital of the Japanese Foundation for Cancer Research, Tokyo; Katsuyuki Kiura, Okayama University Hospital, Okayama; Takashi Seto, National Kyusyu Cancer Center, Fukuoka; Kazuhiko Nakagawa, Kindai University, Osaka-Sayama; Makoto Maemondo, Miyagi Cancer Center, Natori; Akira Inoue, Tohoku University, Sendai; Toyoaki Hida, Aichi Cancer Center, Nagoya; Hiroshige Yoshioka, Kurashiki Central Hospital, Kurashiki; Masao Harada, Hokkaido Cancer Center, Sapporo; Naoyuki Nogami, National Hospital Organization Shikoku Cancer Center, Matsuyama; and Haruyasu Murakami, Shizuoka Cancer Center, Shizuoka, Japan.
authors.forename: Haruyasu
authors.initials: H
authors.lastname: Murakami
authors.affiliation: Tomohide Tamura, St Luke's International Hospital; Yuichiro Ohe, National Cancer Center Hospital; Hiroshi Kuriki, Tadashi Shimada, and Tomohiro Tanaka, Chugai Pharmaceutical; Kengo Takeuchi, Japanese Foundation for Cancer Research; Makoto Nishio, The Cancer Institute Hospital of the Japanese Foundation for Cancer Research, Tokyo; Katsuyuki Kiura, Okayama University Hospital, Okayama; Takashi Seto, National Kyusyu Cancer Center, Fukuoka; Kazuhiko Nakagawa, Kindai University, Osaka-Sayama; Makoto Maemondo, Miyagi Cancer Center, Natori; Akira Inoue, Tohoku University, Sendai; Toyoaki Hida, Aichi Cancer Center, Nagoya; Hiroshige Yoshioka, Kurashiki Central Hospital, Kurashiki; Masao Harada, Hokkaido Cancer Center, Sapporo; Naoyuki Nogami, National Hospital Organization Shikoku Cancer Center, Matsuyama; and Haruyasu Murakami, Shizuoka Cancer Center, Shizuoka, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kuriki
authors.affiliation: Tomohide Tamura, St Luke's International Hospital; Yuichiro Ohe, National Cancer Center Hospital; Hiroshi Kuriki, Tadashi Shimada, and Tomohiro Tanaka, Chugai Pharmaceutical; Kengo Takeuchi, Japanese Foundation for Cancer Research; Makoto Nishio, The Cancer Institute Hospital of the Japanese Foundation for Cancer Research, Tokyo; Katsuyuki Kiura, Okayama University Hospital, Okayama; Takashi Seto, National Kyusyu Cancer Center, Fukuoka; Kazuhiko Nakagawa, Kindai University, Osaka-Sayama; Makoto Maemondo, Miyagi Cancer Center, Natori; Akira Inoue, Tohoku University, Sendai; Toyoaki Hida, Aichi Cancer Center, Nagoya; Hiroshige Yoshioka, Kurashiki Central Hospital, Kurashiki; Masao Harada, Hokkaido Cancer Center, Sapporo; Naoyuki Nogami, National Hospital Organization Shikoku Cancer Center, Matsuyama; and Haruyasu Murakami, Shizuoka Cancer Center, Shizuoka, Japan.
authors.forename: Tadashi
authors.initials: T
authors.lastname: Shimada
authors.affiliation: Tomohide Tamura, St Luke's International Hospital; Yuichiro Ohe, National Cancer Center Hospital; Hiroshi Kuriki, Tadashi Shimada, and Tomohiro Tanaka, Chugai Pharmaceutical; Kengo Takeuchi, Japanese Foundation for Cancer Research; Makoto Nishio, The Cancer Institute Hospital of the Japanese Foundation for Cancer Research, Tokyo; Katsuyuki Kiura, Okayama University Hospital, Okayama; Takashi Seto, National Kyusyu Cancer Center, Fukuoka; Kazuhiko Nakagawa, Kindai University, Osaka-Sayama; Makoto Maemondo, Miyagi Cancer Center, Natori; Akira Inoue, Tohoku University, Sendai; Toyoaki Hida, Aichi Cancer Center, Nagoya; Hiroshige Yoshioka, Kurashiki Central Hospital, Kurashiki; Masao Harada, Hokkaido Cancer Center, Sapporo; Naoyuki Nogami, National Hospital Organization Shikoku Cancer Center, Matsuyama; and Haruyasu Murakami, Shizuoka Cancer Center, Shizuoka, Japan.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Tanaka
authors.affiliation: Tomohide Tamura, St Luke's International Hospital; Yuichiro Ohe, National Cancer Center Hospital; Hiroshi Kuriki, Tadashi Shimada, and Tomohiro Tanaka, Chugai Pharmaceutical; Kengo Takeuchi, Japanese Foundation for Cancer Research; Makoto Nishio, The Cancer Institute Hospital of the Japanese Foundation for Cancer Research, Tokyo; Katsuyuki Kiura, Okayama University Hospital, Okayama; Takashi Seto, National Kyusyu Cancer Center, Fukuoka; Kazuhiko Nakagawa, Kindai University, Osaka-Sayama; Makoto Maemondo, Miyagi Cancer Center, Natori; Akira Inoue, Tohoku University, Sendai; Toyoaki Hida, Aichi Cancer Center, Nagoya; Hiroshige Yoshioka, Kurashiki Central Hospital, Kurashiki; Masao Harada, Hokkaido Cancer Center, Sapporo; Naoyuki Nogami, National Hospital Organization Shikoku Cancer Center, Matsuyama; and Haruyasu Murakami, Shizuoka Cancer Center, Shizuoka, Japan.
authors.forename: Kengo
authors.initials: K
authors.lastname: Takeuchi
authors.affiliation: Tomohide Tamura, St Luke's International Hospital; Yuichiro Ohe, National Cancer Center Hospital; Hiroshi Kuriki, Tadashi Shimada, and Tomohiro Tanaka, Chugai Pharmaceutical; Kengo Takeuchi, Japanese Foundation for Cancer Research; Makoto Nishio, The Cancer Institute Hospital of the Japanese Foundation for Cancer Research, Tokyo; Katsuyuki Kiura, Okayama University Hospital, Okayama; Takashi Seto, National Kyusyu Cancer Center, Fukuoka; Kazuhiko Nakagawa, Kindai University, Osaka-Sayama; Makoto Maemondo, Miyagi Cancer Center, Natori; Akira Inoue, Tohoku University, Sendai; Toyoaki Hida, Aichi Cancer Center, Nagoya; Hiroshige Yoshioka, Kurashiki Central Hospital, Kurashiki; Masao Harada, Hokkaido Cancer Center, Sapporo; Naoyuki Nogami, National Hospital Organization Shikoku Cancer Center, Matsuyama; and Haruyasu Murakami, Shizuoka Cancer Center, Shizuoka, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Nishio
mesh_terms: D000328:Adult; D000368:Aged; D000077548:Anaplastic Lymphoma Kinase; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D002227:Carbazoles / Q000009:adverse effects / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000737:chemistry / Q000188:drug therapy* / Q000556:secondary; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D006932:Hyperbilirubinemia / Q000139:chemically induced; D008175:Lung Neoplasms / Q000737:chemistry / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D010880:Piperidines / Q000009:adverse effects / Q000627:therapeutic use*; D020794:Receptor Protein-Tyrosine Kinases / Q000032:analysis / Q000037:antagonists & inhibitors*; D019233:Retreatment; D015996:Survival Rate; D063189:Symptom Assessment; D013997:Time Factors
chemical_list: D000970:Antineoplastic Agents; D002227:Carbazoles; D010880:Piperidines; C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; D020794:Receptor Protein-Tyrosine Kinases; C582670:alectinib