CH5424802 (RO5424802) for patients with ALK-rearranged advanced non-small-cell lung cancer (AF-001JP study): a single-arm, open-label, phase 1–2 study

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

doi:10.1016/s1470-2045(13)70142-6

Cited by 531 publications

(430 citation statements)

References 21 publications

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“…The incidence of BM in patients with ALK + NSCLC ranges from 20% to 30%, which could be compared with those observed in EGFR‐mutated NSCLC patients 69, 70. Furthermore, ALK‐rearranged NSCLC patients who have not treated with ALK therapy, exhibited a high incidence of CNS metastasis from approximately 45%‐70%, implying that BM is the most common pattern in ALK + NSCLC with therapy failure 71, 72. The production of anaplastic lymphoma kinase with the echinoderm microtubule‐associated protein‐like 4 (EML4‐ALK) fusion tyrosine kinase is the most common changes 73.…”

Section: The Mechanism Of Brain Metastasismentioning

confidence: 96%

Emerging findings into molecular mechanism of brain metastasis

Chen

2018

Cancer Medicine

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Brain metastasis is an important cause of morbidity and mortality in cancer patients. Hence, the need to develop improved therapies to prevent and treat metastasis to the brain is becoming urgent. Recent studies in this area are bringing about some advanced progress on brain metastasis. It was concluded that the occurrence and poor prognosis of brain metastasis have been mostly attributed to the exclusion of anticancer drugs from the brain by the blood‐brain barrier. And several highly potent new generation targeted drugs with enhanced CNS distribution have been developed constantly. However, the noted “seed and soil” hypothesis also suggests that the outcome of metastasis depends on the relationship between unique tumor cells and the specific organ microenvironment. Moreover, increasing studies in multiple tumor types demonstrated that brain metastasis has great molecular differences between primary tumors and extracranial metastasis to a large extent. Here, the authors summarized the most common malignancies that could lead to brain metastasis—lung cancer, breast cancer and melanoma and their related mutated factors. Only by comprehending a deeper understanding of the molecular mechanisms, more effective brain‐specific therapies will be developed for brain metastasis.

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Section: The Mechanism Of Brain Metastasismentioning

confidence: 96%

Emerging findings into molecular mechanism of brain metastasis

Chen

2018

Cancer Medicine

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“…Recent improvements in pathogenic oncogenes for tumor progression have become a novel therapeutic target for the treatment of NSCLC. Many kinase inhibitors such as EGFR kinase inhibitors and anaplastic lymphoma kinase inhibitors have presented a possibility of individualized treatment [4][5][6]19,20] . Our patient gained a considerable survival benefit through the administration of afatinib of waterdispersion type via nasogastric tube in the ICU.…”

Section: Resultsmentioning

confidence: 99%

Successful afatinib treatment through nasogastric tube in a ventilated patient with non-small cell lung cancer

Karasuno¹,

Nishiura²,

Takamori³

et al. 2017

Adv Mod Oncol Res

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The majority of lung cancer patients are discovered at advanced stages and some of them may often have complex medical problems in addition to the diagnosis of cancer, such as oncologic emergency requiring assistance in an intensive care unit (ICU). In the last decade, epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors have been recognized as key drugs for non-small cell lung cancer (NSCLC) harboring sensitive EGFR mutation. We report a case of stage IV NSCLC with EGFR mutation (exon 19 deletion). He was in a life-threatening stage due to a massive intrathoracic hemorrhage. After chest tube drainage and mechanical ventilation, afatinib was administered through nasogastric tube. Consequently, a dramatic response was obtained and he was able to be discharged from our hospital 11 weeks after the initiation of afatinib. This approach may be of benefit to rescue from life-threatening condition for selected patients.Keywords: afatinib; non-small cell lung cancer; EGFR mutation; intensive care unit; mechanical ventilation; waterdispersion type

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“…In the phase II portion of the trial, 46 ALK inhibitor-naïve patients were treated with 300 mg twice daily of alectinib. This drug displayed an excellent RR in both moments of the study (93.5% in the phase II cohort), with long response durations and an acceptable toxicity profile (73). Two complete responses and 41 partial responses were achieved among the 46 evaluable patients, and the two-year PFS rate was 76%.…”

Section: Alectinibmentioning

confidence: 94%

Tackling ALK in non-small cell lung cancer: the role of novel inhibitors

Facchinetti¹,

Tiseo²,

Maïo³

et al. 2016

Transl. Lung Cancer Res.

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Abstract:Crizotinib is an oral inhibitor of anaplastic lymphoma kinase (ALK) with remarkable clinical activity in patients suffering from ALK-rearranged non-small cell lung cancer (NSCLC), accounting to its superiority compared to chemotherapy. Unfortunately, virtually all ALK-rearranged tumors acquire resistance to crizotinib, frequently within one year since the treatment initiation. To date, therapeutic strategies to overcome crizotinib resistance have focused on the use of more potent and structurally different compounds. Second-generation ALK inhibitors such as ceritinib (LDK378), alectinib (CH5424802/ RO5424802) and brigatinib (AP26113) have shown relevant clinical activity, consequently fostering their rapid clinical development and their approval by health agencies. The third-generation inhibitor lorlatinib (PF-06463922), selectively active against ALK and ROS1, harbors impressive biological potency; its efficacy in reversing resistance to crizotinib and to other ALK inhibitors is being proven by early clinical trials. The NTRK1-3 and ROS1 inhibitor entrectinib (RXDX-101) has been reported to act against NSCLC harboring ALK fusion proteins too. Despite the quick development of these novel agents, several issues remain to be discussed in the treatment of patients suffering from ALK-rearranged NSCLC. This position paper will discuss the development, the current evidence and approvals, as long as the future perspectives of new ALK inhibitors beyond crizotinib. Clinical behaviors of ALK-rearranged NSCLC vary significantly among patients and differential molecular events responsible of crizotinib resistance account for the most important quote of this heterogeneity. The precious availability of a wide range of active anti-ALK compounds should be approached in a critical and careful perspective, in order to develop treatment strategies tailored on the disease evolution of every single patient.

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CH5424802 (RO5424802) for patients with ALK-rearranged advanced non-small-cell lung cancer (AF-001JP study): a single-arm, open-label, phase 1–2 study

Cited by 531 publications

References 21 publications

Emerging findings into molecular mechanism of brain metastasis

Emerging findings into molecular mechanism of brain metastasis

Successful afatinib treatment through nasogastric tube in a ventilated patient with non-small cell lung cancer

Tackling ALK in non-small cell lung cancer: the role of novel inhibitors

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