Real-World Clinical Outcomes of Crizotinib Treatment in ALK-Positive Non–Small Cell Lung Cancer Patients with Brain Metastases

Volume 98  Number 1  2017

Posters

Abstract 135; Table 1 All Patients (nZ303)

First-Line (nZ104)

Second-/ Later-Line (nZ199)

Complete response (CR) 3.6% 2.9% 4.0% Partial response (PR) 62.1% 68.3% 58.8% ORR (CR + PR) 65.7% 71.2% 62.8% Median PFS (95% CI), 7.1 (6.7, 7.8) 7.3 (6.6, 8.5) 7.0 (6.6, 8.0) months Median OS (95% CI), 20.4 (18.6, 22.6) 20.6 (17.0, 25.2) 20.4 (18.2, 22.9) months

136 Real-World Clinical Outcomes of Crizotinib Treatment in ALK-Positive NoneSmall Cell Lung Cancer Patients with Brain Metastases K.L. Davis,1 C. Lenz,2 K. Houghton,1 and J.A. Kaye3; 1RTI Health Solutions, Research Triangle Park, NC, 2Pfizer Deutschland GmbH, Berlin, Germany, 3RTI Health Solutions, Waltham, MA Purpose/Objective(s): Brain metastases are reported in 15%-35% of patients with anaplastic lymphoma kinase-positive (ALK+) nonesmall cell lung cancer (NSCLC). Crizotinib has proven efficacy against ALK+ tumors, but its outcomes in recipients with co-occurring brain metastases have not been widely assessed in real-world settings, particularly in Europe (EU). The objective of this analysis was to therefore assess clinical outcomes in an EU population of ALK+ NSCLC patients with brain metastases treated with crizotinib in routine practice. Materials/Methods: A retrospective medical record review was conducted in selected EU countries for adults (18 years) with ALK+ NSCLC treated with crizotinib as first- or later-line therapy for metastatic disease between October 1, 2012 and July 1, 2015. Patients with brain metastases prior crizotinib initiation were selected for sub-analysis. Patients receiving crizotinib in an interventional trial were excluded. Applicable IRB approvals were obtained. Physicians and research staff at participating sites abstracted the study data. Patient data were de-identified, anonymized, and pooled across countries. Descriptive analyses were conducted to assess clinician-documented systemic overall response rate (ORR) and intracranial response (ICR), as well as 1-year overall survival (estimated via Kaplan-Meier). Results: Data were extracted from 303 patients in 5 EU countries, which included a pooled total of 23 patients with brain metastases. Mean (SD) age at diagnosis for these 23 patients was 59.6 (12.6) years and most were male (74%) and had ECOG 0 or 1 (87%). Adenocarcinoma was the most common histology (87%). Approximately half (52%) received whole brain radiation therapy (nZ9) or stereotactic radiosurgery (nZ3) prior to crizotinib initiation. Of the 23 patients studied, 7 received crizotinib as firstline therapy for metastatic disease and 16 received it in second/later line. Sixteen patients were deceased at record abstraction. In first-line crizotinib users, systemic ORR was 57.1% and 1-year survival was 71.4%. Additional results are presented in the table. Conclusion: Systemic ORR in ALK+ NSCLC patients with brain metastases may be more favorable in first-line crizotinib users. ORR (43.8%) and ICR (31.2%) for later-line crizotinib users were consistent with a recent study of later-line crizotinib users with brain metastases pooled from the PROFILE 1005 and 1007 trials reporting a 46%-53% ORR and 18%-33% ICR. Although the ICR observed here cannot be attributed to crizotinib due to possible confounding from pre-crizotinib cranial radiation therapy, our findings indicate that outcomes in crizotinib-treated ALK+ NSCLC patients with brain metastases in clinical studies may translate to regular practice. Abstract 136; Table 1

ORR ICR 1-year survival

All Patients (nZ23)

First-ine (nZ7)

Second-/Later-Line (nZ16)

47.8% 43.5% 52.2%

57.1% 71.4% 71.4%

43.8% 31.2% 43.8%

239

Author Disclosure: K.L. Davis: Research Grant; Pfizer Deutschland GmbH. C. Lenz: Stock; Pfizer Deutschland GmbH. K. Houghton: Research Grant; Pfizer Deutschland GmbH. J.A. Kaye: Research Grant; Pfizer Deutschland GmbH.

137 Case Series of MET Exon 14 Skipping Mutation-positive NoneSmall Cell Lung Cancers and Response to Crizotinib S.X. Wang,1 B. Zhang,1 H.A. Wakelee,2 M. Diehn,2 C. Kunder,1 and J.W. Neal2; 1Stanford Hospital & Clinics, Palo Alto, CA, 2Stanford Cancer Institute, Stanford, CA Purpose/Objective(s): The mesenchymal-to-epithelial transition (MET) gene is a potential new targetable driver mutation in nonesmall cell lung cancer (NSCLC). We describe our institutional experience treating patients with MET exon 14 skipping (METex14) mutations, including response to crizotinib, a MET inhibitor. Materials/Methods: We identified cases of NSCLC with METex14 mutations using an institutionally developed hybrid capture-based or a commercial next-generation sequencing assay. We assessed patient and disease characteristics and response to targeted therapies by retrospective chart review. Results: Fourteen patients were identified: median age was 76.5 years (range: 56-86), 28.6% were women, 35.7% were never-smokers. Stage distribution included 28.5% stage I, 7.1% stage II, 7.1% stage III, and 57.3% stage IV. Six patients were treated with crizotinib, with outcomes as follows: 1) A 67-yearold Asian woman with stage IV adenocarcinoma with three prior lines of chemotherapy had metastatic pleural and rib disease. She started crizotinib with side effects of dizziness and bradycardia. A PET/CT scan after 3 months showed near complete response with resolution of pleural disease and minimal residual FDG activity in bone metastases. 2) A 77-year-old Caucasian woman with stage IV adenocarcinoma progressed after platinum/pemetrexed with response and nivolumab without response. She started crizotinib but developed angioedema after 10 days, requiring drug cessation. She failed therapy rechallenge and her response is pending. 3) A 56-year-old female with stage IV poorly differentiated adenocarcinoma and concurrent MET amplification progressed through two lines of chemotherapies. A two-month CT scan after starting crizotinib showed stable disease. She experienced significant pain and fatigue and pursued hospice. 4) A 73-year-old male with stage IIb METex14 squamous cell lung cancer had recurrent disease and received nivolumab with development of severe immune-related encephalitis. He started crizotinib but his mental status did not recover and he pursued hospice. 5) A 78-year-old male with stage IV adenocarcinoma progressed after platinum/pemextred and nivolumab with mixed response. He started crizotinib but developed fatal pneumonitis after two weeks of therapy. 6) A 62-year-old Asian male with stage IVadenocarcinoma with four prior lines of chemotherapy had metastatic bone and brain disease. He started crizotinib and developed intolerable gastrointestinal side effects. He underwent a 1-week drug holiday and restarted at half dose with dose escalation. He now tolerates full dose therapy with response pending. Conclusion: Our findings showcase the diversity in presentation and histology of NSCLC with METex14 mutations. We report evidence of tumor response to crizotinib, supporting the prior reports that METex14 mutations in NSCLC are actionable driver events. Author Disclosure: S.X. Wang: None. B. Zhang: None. H.A. Wakelee: None. M. Diehn: None. C. Kunder: None. J.W. Neal: Research Grant; Genentech/Rouche, Merck, ArQule, Novartis, Exelixis, Boehringer Ingelheim, Nektar, ARIAD. Consultant; Clovis Oncology, CARET, Nektar, Boehringer Ingelheim, ARMO BioSciences, ARIAD.

138 Endo-Bronchial Valve Placement to Manage Bronchopleural Fistula in Patients with Primary Pulmonary Neoplasm D. Nader, and J. Kucinski; Cancer Treatment Centers of America, Tulsa, OK Purpose/Objective(s): The primary objective of this investigation is to determine efficacy of Intra-bronchial Valve (IBV) placement for the