Pooled Analysis of CNS Response to Alectinib in Two Studies of Pretreated Patients With ALK-Positive Non-Small-Cell Lung Cancer

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.

Conflict of interest statement

Pooled Analysis of CNS Response to Alectinib in Two Studies of Pretreated Patients With

The following represents disclosure information provided by authors of this manuscript. All relationships are considered compensated. Relationships are self-held unless noted. I = Immediate Family Member, Inst = My Institution. Relationships may not relate to the subject matter of this manuscript. For more information about ASCO's conflict of interest policy, please refer to www.asco.org/rwc or jco.ascopubs.org/site/ifc.

Shirish M. Gadgeel

Consulting or Advisory Role: Pfizer, Novartis, Boehringer Ingelheim, Genentech, ARIAD, AstraZeneca, Bristol-Myers Squibb

Speakers' Bureau: Genentech, AstraZeneca

Research Funding: Pfizer (Inst), Clovis Oncology (Inst), Merck (Inst), Genentech (Inst), Incyte (Inst), Millennium (Inst), AstraZeneca/MedImmune (Inst), Bristol-Myers Squibb (Inst), Halozyme Therapeutics (Inst), Acerta Pharma (Inst), ACEA Biosciences (Inst), Janssen Oncology (Inst), Novartis (Inst), Five Prime Therapeutics (Inst), OncoMed (Inst)

Alice T. Shaw

Honoraria: Pfizer, Roche, Novartis

Consulting or Advisory Role: Pfizer, Novartis, Genentech, ARIAD, Roche, Daiichi Sankyo, EMD Serono, Taiho Pharmaceutical, Ignyta

Research Funding: Pfizer, Novartis, Genentech, ARIAD

Ramaswamy Govindan

Honoraria: Boehringer Ingelheim

Consulting or Advisory Role: GlaxoSmithKline, Boehringer Ingelheim, Clovis Oncology, Helsinn Therapeutics, Genentech, Abbvie, Celgene, Bayer, Novartis

Research Funding: Bayer (Inst), GlaxoSmithKline (Inst), MethylGene (Inst), Abbvie (Inst)

Travel, Accommodations, Expenses: Boehringer Ingelheim, Celgene, Merck, Amgen, Genentech, GlaxoSmithKline

Leena Gandhi

Honoraria: Merck

Consulting or Advisory Role: Genentech, Merck, Abbvie, AstraZeneca, Pfizer

Research Funding: Bristol-Myers Squibb

Mark A. Socinski

Honoraria: Genentech

Consulting or Advisory Role: Genentech

Speakers' Bureau: Genentech

Research Funding: Genentech (Inst)

D. Ross Camidge

Honoraria: Genentech

Consulting or Advisory Role: Genentech

Luigi De Petris

Honoraria: F. Hoffman-La Roche, AstraZeneca, Novartis, Quiagen

Consulting or Advisory Role: F. Hoffman-La Roche (Inst), Bristol Meyer-Squibb (Inst), Boehringer Ingelheim (Inst)

Dong-Wan Kim

No relationship to disclose

Alberto Chiappori

Consulting or Advisory Role: Clovis Oncology, Novartis, Genentech, ARIAD

Speakers' Bureau: Pfizer, Novartis, Genentech, Celgene, Boehringer Ingelheim, Merck

Research Funding: Novartis, Pfizer

Denis L. Moro-Sibilot

Honoraria: Roche, Novartis, Pfizer, ARIAD

Consulting or Advisory Role: Roche, Novartis, Pfizer

Travel, Accommodations, Expenses: Roche, Novartis, Pfizer

Michael Duruisseaux

Honoraria: Novartis

Travel, Accommodations, Expenses: Novartis, Roche, Boehringer Ingelheim, Pfizer

Lucio Crino

Honoraria: Pfizer, Boehringer Ingelheim, Bristol-Myers Squibb

Consulting or Advisory Role: Pfizer, Bristol-Myers Squibb

Travel, Accommodations, Expenses: Pfizer, Bristol-Myers Squibb

Tommaso De Pas

No relationship to disclose

Eric Dansin

Honoraria: Roche

Consulting or Advisory Role: AstraZeneca, Eli Lilly, Boehringer Ingelheim, Novartis

Research Funding: Roche (Inst)

Travel, Accommodations, Expenses: Eli Lilly, Novartis, Ipsen

Antje Tessmer

Honoraria: Novartis/Pfizer, Bristol-Myers Squibb

Consulting or Advisory Role: Chugai Pharma

Research Funding: PPD Germany (Inst)

Travel, Accommodations, Expenses: Boehringer Ingelheim

James Chih-Hsin Yang

Honoraria: Boehringer Ingelheim, Roche, Chugai Pharma, MSD, AstraZeneca

Consulting or Advisory Role: Boehringer Ingelheim, Novartis, AstraZeneca, Genentech, Clovis Oncology, Eli Lilly, MSD Oncology, Merck Serono, Celgene, Astellas Pharma, Bayer, Pfizer, Ono Pharmaceutical, Bristol-Myers Squibb, Boehringer Ingelheim (Inst), AstraZeneca (Inst)

Ji-Youn Han

Honoraria: Roche, Pfizer, AstraZeneca

Consulting or Advisory Role: MSO, Bristol-Myers Squibb, Novartis

Research Funding: Roche, Boehringer Ingelheim

Walter Bordogna

Employment: F. Hoffmann-La Roche

Stock or Other Ownership: F. Hoffmann-La Roche

Sophie Golding

Employment: F. Hoffmann-La Roche, F. Hoffmann-La Roche (I)

Stock or Other Ownership: F. Hoffman-La Roche

Ali Zeaiter

Employment: F. Hoffman-La Roche

Stock or other Ownership: F. Hoffman-La Roche

Sai-Hong Ignatius Ou

Honoraria: Genentech, Pfizer, AstraZeneca, Novartis, Boehringer Ingelheim

Consulting or Advisory Role: Genentech, Pfizer, ARIAD, Novartis

Speakers' Bureau: Genentech, AstraZeneca, Boehringer Ingelheim, Novartis

Research Funding: Pfizer (Inst), Genentech (Inst), ARIAD (Inst), AstraZeneca/MedImmune (Inst), Clovis Oncology (Inst), Daiichi Sankyo (Inst), Boehringer Ingelheim (Inst), Ignyta (Inst)

Figures

Fig 1.

Waterfall plot of best CNS response in patients with baseline measurable CNS disease by prior CNS radiation.