Journal Thoracic Oncology

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Abstracts Journal of Thoracic Oncology • Volume 12 Issue S1 January 2017 five (31.3%) an ECOG performance status of 0, and all had stage IV disease. Median time from primary site diagnosis to ceritinib initiation (range) was 1.8 months (1.0–35.9). At data cut-off, median duration of exposure (range) was 18.5 months (0.9–35.7) and median duration of follow-up (range) was 29.6 months (4.7–39.1). In these 16 treatment-naïve patients, per investigator assessment, the overall response rate was 68.8% (95% confidence interval [CI]: 41.3, 89.0) and the disease control rate was 87.5% (95% CI: 61.7, 98.4). Median duration of response was 21.1 months (95% CI: 5.5, 31.1). Median investigator-assessed PFS was 19.3 months (95% CI: 4.2, 26.3), and median overall survival was 39.1 months (95% CI: 19.1, 39.1). Among three patients with baseline brain metastases, one had brain metastases selected as target lesion and achieved a partial intracranial response. The most frequently reported any-grade adverse events (AEs), regardless of study drug relationship, were diarrhea (93.8%), nausea (81.3%), ALT or AST increase (each 81.3%), and vomiting (62.5%). AEs requiring intervention were predominantly managed with dose reduction/interruption. Overall, 13 patients (81.3%) discontinued treatment, due to disease progression (n=6), consent withdrawal (n=3), AEs (n=2), administrative problems or death (each n=1). Conclusion: Ceritinib demonstrated durable efficacy in treatment-naïve patients with ALK+ NSCLC. Safety was consistent with the overall ASCEND-1 study population. An ongoing, prospective, phase 3 study (ASCEND-4) in which patients are randomized to receive either ceritinib or chemotherapy will provide further evidence for the clinical benefit of ceritinib in previously untreated patients with ALK+ NSCLC. Keywords: Ceritinib, treatment naïve, ALK+ NSCLC POSTER SESSION 3 – P3.02A: ADVANCED NSCLC & CHEMOTHERAPY/TARGETED THERAPY/ IMMUNOTHERAPY ALK CLINICAL – WEDNESDAY, DECEMBER 7, 2016 P3.02A-016 POOLED EFFICACY AND SAFETY DATA FROM TWO PHASE II STUDIES (NP28673 AND NP28761) OF ALECTINIB IN ALK+ NON-SMALL-CELL LUNG CANCER (NSCLC) James Chih-Hsin Yang 1 , Sai-Hong Ou 2 , Luigi De Petris 3 , Shirish Gadgeel 4 , Leena Gandhi 5 , Dong-Wan Kim 6 , Fabrice Barlesi 7 , Ramaswamy Govindan 8 , Anne-Marie Dingemans 9 , Lucio Crinò 10 , Hervé Léna 11 , Sanjay Popat 12 , Jin Seok Ahn 13 , Eric Dansin 14 , Sophie Golding 15 , Walter Bordogna 15 , Bogdana Balas 15 , Peter N. Morcos 16 , Ali Zeaiter 15 , Alice Shaw 17 1 Graduate Institute of Oncology, National Taiwan University, Taipei/Taiwan, 2 Chao Family Comprehensive Cancer Centre, University of California Irvine School of Medicine, Orange/CA/United States of America, 3 Oncology, Karolinska University Hospital, Stockholm/Sweden, 4 Karmanos Cancer Institute; Wayne State University, Detroit/MI/United States of America, 5 Dana-Farber Cancer Institute, Boston/ MA/United States of America, 6 Seoul National University Hospital, Seoul/Korea, Republic of, 7 Aix-Marseille University; Assistance Publique Hôpitaux de Marseille, Marseille/France, 8 Department of Internal Medicine, Washington University School of Medicine, St. Louis/MO/United States of America, 9 Pulmonary Diseases, Maastricht University Medical Centre, Maastricht/Netherlands, 10 Perugia University Hospital, Perugia/Italy, 11 Centre Hospitalier Universitaire de Rennes, Rennes/France, 12 Royal Marsden Hospital; Imperial College, London/United Kingdom, 13 Samsung Medical Center, Seoul/Korea, Republic of, 14 Clcc Oscar- Lambret, Lille/France, 15 F. Hoffmann-La Roche Ltd, Basel/Switzerland, 16 Roche, New York/NY/United States of America, 17 Massachusetts General Hospital Cancer Center; Harvard Medical School, Boston/MA/United States of America (95% CI 7.0–11.3) after 69% of events and median OS was 26.0 months (95% CI 21.4–NE) after 43% of events. Grade ≥3 adverse events (AEs) occurred in 40% of patients and the most common were dyspnoea (4%), elevated levels of blood creatine phosphokinase (4%) and alanine aminotransferase (3%). The mean dose intensity was 94.6%. Fourteen patients withdrew due to AEs; 20.9% had AEs leading to dose interruptions/modification. Conclusion: This pooled analysis confirmed alectinib has robust systemic efficacy with a durable response in this population and in patients with or without prior chemotherapy. Alectinib had an acceptable safety profile. Keywords: NSCLC, ALK-inhibitor, Alectinib, phase II pooled analysis POSTER SESSION 3 – P3.02A: ADVANCED NSCLC & CHEMOTHERAPY/TARGETED THERAPY/ IMMUNOTHERAPY ALK CLINICAL – WEDNESDAY, DECEMBER 7, 2016 P3.02A-017 INDIRECT NAIVE COMPARISON OF POST-CRIZOTINIB TREATMENTS FOR ALK+ NON–SMALL-CELL LUNG CANCER (NSCLC) Karen Reckamp 1 , Joice Huang 2 , Hui Huang 2 1 City of Hope Comprehensive Cancer Center, Duarte/CA/United States of America, 2 Ariad Pharmaceuticals, Inc., Cambridge/MA/United States of America Background: Comparing the efficacy of ALK inhibitors in post-crizotinib therapy of ALK+ NSCLC is hampered by the lack of comparator ALK inhibitor treatment arms in pivotal studies. An indirect naive comparison was undertaken to explore study results for the investigational ALK inhibitor brigatinib and the currently available agents alectinib and ceritinib following progression on crizotinib. Baseline characteristics were examined to determine if the distribution of prognostic factors differed across studies, and outcomes were compared. Methods: Patient characteristics and study outcomes (objective response rate [ORR], progression-free survival [PFS], duration of response [DOR], and adverse events [AEs]) for alectinib, brigatinib, and ceritinib were extracted from pivotal study publications identified in a systematic literature review, alectinib prescribing information, and brigatinib data in post-crizotinib settings. Outcomes were compared over the longest follow-ups reported. Results: All pivotal studies were multicenter and open label; populations were similar in median age, sex ratio, and baseline disease stage. Slight imbalances among studies exist in Eastern Cooperative Oncology Group/World Health Organization performance status and central nervous system metastases at baseline. ORR was numerically higher in the brigatinib phase 1/2 study for subjects receiving 180 mg once daily with 7-day lead-in at 90 mg versus other studies (Table). Median PFS and DOR were also higher in brigatinib studies versus alectinib and ceritinib studies; PFS 95% confidence intervals did not overlap between brigatinib and ceritinib studies. Rates of discontinuation due to AEs were similar across studies, but AErelated dose reductions were most frequent in ceritinib studies. (See Table next page) Background: Alectinib is an FDA-approved ALK TKI, for treatment of patients with ALK+ metastatic NSCLC who have progressed on, or are intolerant to, crizotinib. Systemic and CNS efficacy was demonstrated in two single-arm, phase II studies (NP28673 [NCT01801111] and NP28761 [NCT01871805]). We report the pooled systemic efficacy and safety analysis of alectinib from 2016 cut-offs 22 January, NP28761 and 1 February, NP28673. Methods: Patients were ≥18 years, had locally advanced or metastatic ALK+ NSCLC [FDA-approved FISH test] and had progressed on, or were intolerant to, crizotinib. Patients received oral alectinib 600mg twice daily until disease progression, death or withdrawal. The pooled analysis assessed objective response rate (ORR) by an independent review committee (IRC) using RECIST v1.1 (primary endpoint in both studies); disease control rate (DCR); duration of response (DOR); progression-free survival (PFS); overall survival (OS); and safety. Results: The pooled dataset included 225 patients, (n=138 NP28673; n=87 NP28761). Median age was 53 years, 60% of patients had baseline CNS metastases and 77% had received prior chemotherapy. The responseevaluable (RE) population by IRC included 189 patients (84%). Median follow-up was 18.8 months (0.6–29.7). In the RE population (n=189) ORR by IRC was 51.3% (95% CI 44.0–58.6; all partial responses), a DCR of 78.8% (95% CI 72.3–84.4), with a median DOR of 14.9 months (95% CI 11.1–20.4) after 58% of events. In patients with prior chemotherapy (n=148), IRC ORR was 49.3% (95% CI 41.0–57.7); DCR: 79.1% (95% CI 71.6–85.3); median DOR: 14.9 months (95% CI 11.0–21.9) after 59% of events. In patients who were chemotherapynaïve (n=41), IRC ORR was 58.5% (95% CI 42.1–73.7); DCR: 78.0% (95% CI 62.4–89.4); median DOR: 11.2 months (95% CI 8.0–NE) after 54% of events. In the total pooled population (n=225) median PFS by IRC was 8.3 months S614 Journal of Thoracic Oncology • Volume 12 Issue S1 January 2017
Abstracts Journal of Thoracic Oncology • Volume 12 Issue S1 January 2017 Conclusion: Pivotal trials for ALK inhibitors share many similarities, making an indirect comparison possible. Naive comparison suggests brigatinib may have a favorable efficacy profile compared with currently available therapies, while ceritinib may require dose reduction more frequently to manage AEs. Further analyses are needed to determine the magnitude and direction of potential bias. Keywords: brigatinib, Ceritinib, non–Small-Cell Lung Cancer, Alectinib POSTER SESSION 3 – P3.02A: ADVANCED NSCLC & CHEMOTHERAPY/TARGETED THERAPY/ IMMUNOTHERAPY ALK CLINICAL – WEDNESDAY, DECEMBER 7, 2016 P3.02A-018 EFFICACY OF PEMETREXED BASED CHEMOTHERAPY COMPARED WITH NON-PEMETREXED BASED CHEMOTHERAPY IN ADVANCED, ALK-POSITIVE NSCLC Jaemin Jo 1 , Se Hyun Kim 1 , Yu Jung Kim 1 , Miso Kim 2 , Bhumsuk Keam 2 , Tae Min Kim 2 , Dong-Wan Kim 2 , Dae Seog Heo 2 , Jong Seok Lee 1 1 Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam-Si/Korea, Republic of, 2 Seoul National University Hospital, Seoul/Korea, Republic of Background: Previous retrospective studies suggested that lung cancer patients with anaplastic lymphoma kinase (ALK) gene rearrangements are associated with sensitivity to pemetrexed chemotherapy. To determine the efficacy of pemetrexed based chemotherapy compared with non-pemetrexed based chemotherapy, we retrospectively evaluated clinical outcome in ALK positive non-small cell lung cancer (NSCLC) patients. Methods: We identified 126 patients with advanced, ALK-positive NSCLC who received 1st line cytotoxic chemotherapy from Seoul National University Hospital and Seoul National University Bundang Hospital. We compared response rate, progression-free survival, and overall survival according to chemotherapy regimens. We also analyzed the intra-cranial time to progression and proportion of ALK-positive cells as a predictive factor of pemetrexed efficacy. Results: Forty eight patients received pemetrexed based chemotherapy and Seventy eight patients received non-pemetrexed based chemotherapy as first line systemic treatment. One hundred eighteen patients received platinum double combination chemotherapy. The pemetrexed based chemotherapy group shows superior overall response rate (44.7% versus 14.3%, p
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LILLY ONCOLOGY IS DEDICATED TO ADVA
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