Pooled analysis of CNS response to alectinib in two studies of pretreated patients with ALK-positive non-small-cell lung cancer

Shirish M. Gadgeel, Alice T. Shaw, Ramaswamy Govindan, Leena Gandhi, Mark A. Socinski, D. Ross Camidge, Luigi De Petris, Dong Wan Kim, Alberto Chiappori, Denis L. Moro-Sibilot, Michael Duruisseaux, Lucio Crino, Tommaso De Pas, Eric Dansin, Antje Tessmer, James Chih Hsin Yang, Ji Youn Han, Walter Bordogna, Sophie Golding, Ali ZeaiterSai Hong Ignatius Ou

Research output: Contribution to journalArticle

Abstract

Purpose: Alectinib has shown activity in the CNS in phase I and II studies. To further evaluate this activity, we pooled efficacy and safety data from two single-arm phase II studies (NP28761 and NP28673; ClinicalTrials.gov identifiers: NCT01871805 and NCT01801111, respectively) in patients with ALK-positive non-small-cell lung cancer (NSCLC). Patients and Methods: Both studies included patients with ALK-positive NSCLC who had previously received crizotinib; all patients received alectinib 600 mg twice per day. The primary end point in both studies was independent review committee (IRC)-assessed objective response rate (ORR; by Response Evaluation Criteria in Solid Tumors [RECIST] version 1.1). Additional end points (all by IRC) included CNS ORR (CORR), CNS disease control rate (CDCR), and CNS duration of response (CDOR). Results: One hundred thirty-six patients had baseline CNS metastases (60% of the overall study populations); 50 patients (37%) had measurable CNS disease at baseline. Ninety-five patients (70%) had prior CNS radiotherapy; 55 patients completed the CNS radiotherapy more than 6 months before starting alectinib. Median follow-up time was 12.4 months (range, 0.9 to 19.7 months). For patients with baseline measurable CNS disease, IRC CORR was 64.0% (95% CI, 49.2% to 77.1%), CDCR was 90.0% (95% CI, 78.2% to 96.7%), and median CDOR was 10.8 months (95% CI, 7.6 to 14.1 months). For patients with measurable and/or nonmeasurable baseline CNS disease, IRC CORR was 42.6% (95% CI, 34.2% to 51.4%), CDCR was 85.3% (95% CI, 78.2% to 90.8%), and median CDOR was 11.1 months (95% CI, 10.3 months to not evaluable). CORR was 35.8% (95% CI, 26.2% to 46.3%) for patients with prior radiotherapy (n = 95) and 58.5% (95% CI, 42.1% to 73.7%) for patients without prior radiotherapy (n = 41). As previously reported, alectinib was well tolerated, regardless of baseline CNS disease. Conclusion: Alectinib showed good efficacy against CNS metastases, in addition to systemic activity, in crizotinib-refractory ALK-positive NSCLC.

Original languageEnglish
Pages (from-to)4079-4085
Number of pages7
JournalJournal of Clinical Oncology
Volume34
Issue number34
DOIs
Publication statusPublished - Dec 1 2016

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Non-Small Cell Lung Carcinoma
Central Nervous System Diseases
Advisory Committees
Radiotherapy
CH5424802
Neoplasm Metastasis
Safety

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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Gadgeel, S. M., Shaw, A. T., Govindan, R., Gandhi, L., Socinski, M. A., Camidge, D. R., ... Ou, S. H. I. (2016). Pooled analysis of CNS response to alectinib in two studies of pretreated patients with ALK-positive non-small-cell lung cancer. Journal of Clinical Oncology, 34(34), 4079-4085. https://doi.org/10.1200/JCO.2016.68.4639

Pooled analysis of CNS response to alectinib in two studies of pretreated patients with ALK-positive non-small-cell lung cancer. / Gadgeel, Shirish M.; Shaw, Alice T.; Govindan, Ramaswamy; Gandhi, Leena; Socinski, Mark A.; Camidge, D. Ross; De Petris, Luigi; Kim, Dong Wan; Chiappori, Alberto; Moro-Sibilot, Denis L.; Duruisseaux, Michael; Crino, Lucio; De Pas, Tommaso; Dansin, Eric; Tessmer, Antje; Yang, James Chih Hsin; Han, Ji Youn; Bordogna, Walter; Golding, Sophie; Zeaiter, Ali; Ou, Sai Hong Ignatius.

In: Journal of Clinical Oncology, Vol. 34, No. 34, 01.12.2016, p. 4079-4085.

Research output: Contribution to journalArticle

Gadgeel, SM, Shaw, AT, Govindan, R, Gandhi, L, Socinski, MA, Camidge, DR, De Petris, L, Kim, DW, Chiappori, A, Moro-Sibilot, DL, Duruisseaux, M, Crino, L, De Pas, T, Dansin, E, Tessmer, A, Yang, JCH, Han, JY, Bordogna, W, Golding, S, Zeaiter, A & Ou, SHI 2016, 'Pooled analysis of CNS response to alectinib in two studies of pretreated patients with ALK-positive non-small-cell lung cancer', Journal of Clinical Oncology, vol. 34, no. 34, pp. 4079-4085. https://doi.org/10.1200/JCO.2016.68.4639
Gadgeel, Shirish M. ; Shaw, Alice T. ; Govindan, Ramaswamy ; Gandhi, Leena ; Socinski, Mark A. ; Camidge, D. Ross ; De Petris, Luigi ; Kim, Dong Wan ; Chiappori, Alberto ; Moro-Sibilot, Denis L. ; Duruisseaux, Michael ; Crino, Lucio ; De Pas, Tommaso ; Dansin, Eric ; Tessmer, Antje ; Yang, James Chih Hsin ; Han, Ji Youn ; Bordogna, Walter ; Golding, Sophie ; Zeaiter, Ali ; Ou, Sai Hong Ignatius. / Pooled analysis of CNS response to alectinib in two studies of pretreated patients with ALK-positive non-small-cell lung cancer. In: Journal of Clinical Oncology. 2016 ; Vol. 34, No. 34. pp. 4079-4085.
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abstract = "Purpose: Alectinib has shown activity in the CNS in phase I and II studies. To further evaluate this activity, we pooled efficacy and safety data from two single-arm phase II studies (NP28761 and NP28673; ClinicalTrials.gov identifiers: NCT01871805 and NCT01801111, respectively) in patients with ALK-positive non-small-cell lung cancer (NSCLC). Patients and Methods: Both studies included patients with ALK-positive NSCLC who had previously received crizotinib; all patients received alectinib 600 mg twice per day. The primary end point in both studies was independent review committee (IRC)-assessed objective response rate (ORR; by Response Evaluation Criteria in Solid Tumors [RECIST] version 1.1). Additional end points (all by IRC) included CNS ORR (CORR), CNS disease control rate (CDCR), and CNS duration of response (CDOR). Results: One hundred thirty-six patients had baseline CNS metastases (60{\%} of the overall study populations); 50 patients (37{\%}) had measurable CNS disease at baseline. Ninety-five patients (70{\%}) had prior CNS radiotherapy; 55 patients completed the CNS radiotherapy more than 6 months before starting alectinib. Median follow-up time was 12.4 months (range, 0.9 to 19.7 months). For patients with baseline measurable CNS disease, IRC CORR was 64.0{\%} (95{\%} CI, 49.2{\%} to 77.1{\%}), CDCR was 90.0{\%} (95{\%} CI, 78.2{\%} to 96.7{\%}), and median CDOR was 10.8 months (95{\%} CI, 7.6 to 14.1 months). For patients with measurable and/or nonmeasurable baseline CNS disease, IRC CORR was 42.6{\%} (95{\%} CI, 34.2{\%} to 51.4{\%}), CDCR was 85.3{\%} (95{\%} CI, 78.2{\%} to 90.8{\%}), and median CDOR was 11.1 months (95{\%} CI, 10.3 months to not evaluable). CORR was 35.8{\%} (95{\%} CI, 26.2{\%} to 46.3{\%}) for patients with prior radiotherapy (n = 95) and 58.5{\%} (95{\%} CI, 42.1{\%} to 73.7{\%}) for patients without prior radiotherapy (n = 41). As previously reported, alectinib was well tolerated, regardless of baseline CNS disease. Conclusion: Alectinib showed good efficacy against CNS metastases, in addition to systemic activity, in crizotinib-refractory ALK-positive NSCLC.",
author = "Gadgeel, {Shirish M.} and Shaw, {Alice T.} and Ramaswamy Govindan and Leena Gandhi and Socinski, {Mark A.} and Camidge, {D. Ross} and {De Petris}, Luigi and Kim, {Dong Wan} and Alberto Chiappori and Moro-Sibilot, {Denis L.} and Michael Duruisseaux and Lucio Crino and {De Pas}, Tommaso and Eric Dansin and Antje Tessmer and Yang, {James Chih Hsin} and Han, {Ji Youn} and Walter Bordogna and Sophie Golding and Ali Zeaiter and Ou, {Sai Hong Ignatius}",
year = "2016",
month = "12",
day = "1",
doi = "10.1200/JCO.2016.68.4639",
language = "English",
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TY - JOUR

T1 - Pooled analysis of CNS response to alectinib in two studies of pretreated patients with ALK-positive non-small-cell lung cancer

AU - Gadgeel, Shirish M.

AU - Shaw, Alice T.

AU - Govindan, Ramaswamy

AU - Gandhi, Leena

AU - Socinski, Mark A.

AU - Camidge, D. Ross

AU - De Petris, Luigi

AU - Kim, Dong Wan

AU - Chiappori, Alberto

AU - Moro-Sibilot, Denis L.

AU - Duruisseaux, Michael

AU - Crino, Lucio

AU - De Pas, Tommaso

AU - Dansin, Eric

AU - Tessmer, Antje

AU - Yang, James Chih Hsin

AU - Han, Ji Youn

AU - Bordogna, Walter

AU - Golding, Sophie

AU - Zeaiter, Ali

AU - Ou, Sai Hong Ignatius

PY - 2016/12/1

Y1 - 2016/12/1

N2 - Purpose: Alectinib has shown activity in the CNS in phase I and II studies. To further evaluate this activity, we pooled efficacy and safety data from two single-arm phase II studies (NP28761 and NP28673; ClinicalTrials.gov identifiers: NCT01871805 and NCT01801111, respectively) in patients with ALK-positive non-small-cell lung cancer (NSCLC). Patients and Methods: Both studies included patients with ALK-positive NSCLC who had previously received crizotinib; all patients received alectinib 600 mg twice per day. The primary end point in both studies was independent review committee (IRC)-assessed objective response rate (ORR; by Response Evaluation Criteria in Solid Tumors [RECIST] version 1.1). Additional end points (all by IRC) included CNS ORR (CORR), CNS disease control rate (CDCR), and CNS duration of response (CDOR). Results: One hundred thirty-six patients had baseline CNS metastases (60% of the overall study populations); 50 patients (37%) had measurable CNS disease at baseline. Ninety-five patients (70%) had prior CNS radiotherapy; 55 patients completed the CNS radiotherapy more than 6 months before starting alectinib. Median follow-up time was 12.4 months (range, 0.9 to 19.7 months). For patients with baseline measurable CNS disease, IRC CORR was 64.0% (95% CI, 49.2% to 77.1%), CDCR was 90.0% (95% CI, 78.2% to 96.7%), and median CDOR was 10.8 months (95% CI, 7.6 to 14.1 months). For patients with measurable and/or nonmeasurable baseline CNS disease, IRC CORR was 42.6% (95% CI, 34.2% to 51.4%), CDCR was 85.3% (95% CI, 78.2% to 90.8%), and median CDOR was 11.1 months (95% CI, 10.3 months to not evaluable). CORR was 35.8% (95% CI, 26.2% to 46.3%) for patients with prior radiotherapy (n = 95) and 58.5% (95% CI, 42.1% to 73.7%) for patients without prior radiotherapy (n = 41). As previously reported, alectinib was well tolerated, regardless of baseline CNS disease. Conclusion: Alectinib showed good efficacy against CNS metastases, in addition to systemic activity, in crizotinib-refractory ALK-positive NSCLC.

AB - Purpose: Alectinib has shown activity in the CNS in phase I and II studies. To further evaluate this activity, we pooled efficacy and safety data from two single-arm phase II studies (NP28761 and NP28673; ClinicalTrials.gov identifiers: NCT01871805 and NCT01801111, respectively) in patients with ALK-positive non-small-cell lung cancer (NSCLC). Patients and Methods: Both studies included patients with ALK-positive NSCLC who had previously received crizotinib; all patients received alectinib 600 mg twice per day. The primary end point in both studies was independent review committee (IRC)-assessed objective response rate (ORR; by Response Evaluation Criteria in Solid Tumors [RECIST] version 1.1). Additional end points (all by IRC) included CNS ORR (CORR), CNS disease control rate (CDCR), and CNS duration of response (CDOR). Results: One hundred thirty-six patients had baseline CNS metastases (60% of the overall study populations); 50 patients (37%) had measurable CNS disease at baseline. Ninety-five patients (70%) had prior CNS radiotherapy; 55 patients completed the CNS radiotherapy more than 6 months before starting alectinib. Median follow-up time was 12.4 months (range, 0.9 to 19.7 months). For patients with baseline measurable CNS disease, IRC CORR was 64.0% (95% CI, 49.2% to 77.1%), CDCR was 90.0% (95% CI, 78.2% to 96.7%), and median CDOR was 10.8 months (95% CI, 7.6 to 14.1 months). For patients with measurable and/or nonmeasurable baseline CNS disease, IRC CORR was 42.6% (95% CI, 34.2% to 51.4%), CDCR was 85.3% (95% CI, 78.2% to 90.8%), and median CDOR was 11.1 months (95% CI, 10.3 months to not evaluable). CORR was 35.8% (95% CI, 26.2% to 46.3%) for patients with prior radiotherapy (n = 95) and 58.5% (95% CI, 42.1% to 73.7%) for patients without prior radiotherapy (n = 41). As previously reported, alectinib was well tolerated, regardless of baseline CNS disease. Conclusion: Alectinib showed good efficacy against CNS metastases, in addition to systemic activity, in crizotinib-refractory ALK-positive NSCLC.

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