Phase 3 study of ceritinib vs chemotherapy in ALK-rearranged NSCLC patients previously treated with chemotherapy and crizotinib (ASCEND-5): Japanese subset

Kiura, Katsuyuki; Imamura, Fumio; Kagamu, Hiroshi; Matsumoto, Shingo; Hida, Toyoaki; Nakagawa, Kazuhiko; Satouchi, Miyako; Okamoto, Isamu; Takenoyama, Mitsuhiro; Fujisaka, Yasuhito; Kurata, Takeshi; Itô, Masayuki; Tokushige, Kota; Hudson, Ben; Nishio, Makoto

doi:10.1093/jjco/hyy016

Cited by 24 publications

(22 citation statements)

References 18 publications

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“…The tissue EGFR positivity rate among our patients was 25.3%, which is similar to that reported in Indian studies but higher than most Western reports. [ 44 45 46 47 48 49 50 51 52 53 ] However, the ALK positivity rate of 11.5% observed in our study is higher than most previous reports (5% in Western and 1.45%–7.6% in Indian individuals). [ 53 54 55 ] Whether this observation represents a true high prevalence of ALK rearrangements in this geographical region remains unknown yet, and more population-based data is required before we can draw definite conclusions.…”

Section: Discussioncontrasting

confidence: 83%

Clinical profile of lung cancer in North India: A 10-year analysis of 1862 patients from a tertiary care center

et al. 2020

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Introduction: Over the past few years, the demographic profile of lung cancer has changed. However, most reports are limited by small numbers, short follow-up period, and show an inconsistent pattern. A comprehensive evaluation of changing trends over a long period has not been done. Materials and Methods: Consecutive lung cancer patients were studied over a 10-year period from January 2008 to March 2018 at the All India Institute of Medical Sciences, New Delhi, and relevant clinical information, and survival outcomes were analyzed. Results: A total of 1862 patients were evaluated, with mean (SD) age of 59 (11.1) years, and comprising 82.9% males. Majority were smokers (76.2%) with median smoking index of 500 (interquartile range [IQR]: 300–800). Adenocarcinoma (ADC) was the most common type (34%), followed by squamous cell carcinoma (SCC – 28.6%) and small cell lung cancer (SCLC) (16.1%). Over the 10-year period, ADC increased from 9.5% to 35.9%, SCC from 25.4% to 30.6%, and non-small cell lung cancer -not otherwise specified (NSCLC-NOS) decreased from 49.2% to 21.4%. The proportion of females with lung cancer increased although smoking rates remained similar. Majority of NSCLC (95%) continued to be diagnosed at an advanced stage (3 or 4). Epidermal growth factor receptor (EGFR) mutations and anaplastic lymphoma kinase (ALK) rearrangements were present in 25.3% and 11.5% ADC patients, respectively. The median overall survival was 8.8 months (IQR 3.7–19) for all patients and 12.57 (IQR 6.2–28.7) months among the 1013 patients who were initiated on specific treatment (chemotherapy, targeted therapy, radiotherapy, or surgery). Never-smokers were younger, more likely to be female and educated, had a higher prevalence of ADC and EGFR/ALK mutations, and had better survival. Conclusion: Among this large cohort, our center seems to follow the global trend with increasing incidence of ADC. EGFR mutation positivity was similar to existing reports, while higher ALK positivity was detected. A characteristic phenotype of never-smokers with lung cancer was elucidated which demonstrated better survival.

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Section: Discussioncontrasting

confidence: 83%

Clinical profile of lung cancer in North India: A 10-year analysis of 1862 patients from a tertiary care center

et al. 2020

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“…All 20 patients required at least 1 dose adjustment or interruption. Median relative dose intensity in our study with ceritinib 750 mg fasted was 68.6% (range: 30.3-100) which was consistent with that reported in the Japanese population in ASCEND-2 (65.0% [range: 38.5-100.0])26 and ASCEND-5 (71.9% [range: 35.4%-100.0%]) 27. The safety profile of ceritinib was consistent with that previously reported,14,15 with no new or unexpected AE identified.…”

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confidence: 89%

Phase II study of ceritinib in alectinib‐pretreated patients with anaplastic lymphoma kinase‐rearranged metastatic non‐small‐cell lung cancer in Japan: ASCEND‐9

et al. 2018

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Clinical experience of ceritinib in patients who progressed on alectinib is limited. In this prospective phase II study, we evaluated the activity of ceritinib in alectinib‐pretreated patients with anaplastic lymphoma kinase (ALK)‐rearranged metastatic (stage IIIB/IV) non‐small‐cell lung cancer (NSCLC) in Japan. All patients were required to have ≥1 measurable lesion per RECIST, 1.1, and a World Health Organization Performance Status (WHO PS) of 0‐1. Prior crizotinib and/or up to 1 chemotherapy regimen was allowed. Primary endpoint was investigator‐assessed overall response rate (ORR) per RECIST 1.1. Ceritinib was given at a dose of 750 mg/day fasted. A total of 20 patients were enrolled from August 2015 to March 2017. All patients received prior alectinib (100%), 13 (65.0%) patients received prior platinum‐based chemotherapy, and 4 (20%) patients received prior crizotinib. Median duration of exposure and the follow‐up time with ceritinib were 3.7 months (range: 0.4‐15.1) and 11.6 months (range: 4.8‐23.0), respectively. Investigator‐assessed ORR was 25% (95% CI: 8.7‐49.1). Key secondary endpoints, all investigator assessed, included disease control rate (70.0%; 95% CI: 45.7‐88.1), time to response (median, 1.8 months; range: 1.8‐2.0), and duration of response (median, 6.3 months; 95% CI: 3.5‐9.2). Median progression‐free survival was 3.7 months (95% CI: 1.9‐5.3). The most common adverse events reported were diarrhea (85.0%), nausea (80.0%), and vomiting (65.0%). Based on our findings, ceritinib could be considered as one of the treatment options for patients with ALK‐positive NSCLC who progressed on alectinib. (Trial registration no. NCT02450903)

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“…This is especially true for patients with ALKþ NSCLC, where clinical outcome is significantly improved after treatment with an ALK TKI compared to traditional chemotherapy. 4,28 Moreover, the responses of ALKþ NSCLC patients to specific ALK TKIs vary even though they share a molecular driver. 6,8,19 Thus, tracking the evolution of resistance is imperative in this patient population.…”

Section: Discussionmentioning

confidence: 99%

Monitoring Therapeutic Response and Resistance: Analysis of Circulating Tumor DNA in Patients With ALK+ Lung Cancer

Horn

Whisenant

Wakelee

et al. 2019

Journal of Thoracic Oncology

142

138

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Genentech, Tessaro, and Xcovery; and reports receiving commercial research support from Boehringer Ingelheim. Dr. Whisenant has received personal fees from Anasys Instruments. Dr. Wakelee is a consultant/advisory board member for AstraZeneca, Genentech/ Roche (uncompensated), Merck (uncompensated), Novartis (uncompensated), and Ariad (uncompensated); and has received grants to her institution for conduct of clinical trial work from

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Phase 3 study of ceritinib vs chemotherapy in ALK-rearranged NSCLC patients previously treated with chemotherapy and crizotinib (ASCEND-5): Japanese subset

Abstract: This subgroup analysis of ASCEND-5 study demonstrated better efficacy of ceritinib compared with the standard second-line chemotherapy in chemotherapy- and crizotinib-pretreated Japanese patients with ALK-rearranged NSCLC.

Cited by 24 publications

References 18 publications

Clinical profile of lung cancer in North India: A 10-year analysis of 1862 patients from a tertiary care center

Clinical profile of lung cancer in North India: A 10-year analysis of 1862 patients from a tertiary care center

Phase II study of ceritinib in alectinib‐pretreated patients with anaplastic lymphoma kinase‐rearranged metastatic non‐small‐cell lung cancer in Japan: ASCEND‐9

Monitoring Therapeutic Response and Resistance: Analysis of Circulating Tumor DNA in Patients With ALK+ Lung Cancer

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