- Email: [email protected]
paclitaxel: Phase 2 results
Abstracts
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Table (abstract 3089). Wk
6 12 18 24 30
Mean change (standard deviation), n LCSS ASBI All pts PRa
SDa
0.6 (14.2), 557 −1.8 (14.9), 375 −2.5 (13.3), 205 −3.9 (13.7), 95 −2.8 (14.4), 46
−0.7 −2.0 −3.8 −2.8 −3.0
−2.3 −2.4 −1.3 −9.4 −4.2
(12.0), (13.7), (13.8), (12.2), (13.5),
52 53 40 22 12
(13.6), (14.5), (13.4), (14.2), (15.2),
207 183 125 64 28
PDa
EQ-5D VAS All pts
PRa
SDa
2.5 (15.0), 148 −1.0 (16.2), 45 −0.9 (10.3), 18 5.0 (12.4), 4 7.2 (12.0), 4
1.0 5.8 8.2 8.2 8.4
7.3 (22.4), 52 6.6 (24.7), 52 8.1 (27.6), 39 18.1 (31.0), 20 13.7 (38.2), 10
3.8 6.4 8.2 5.2 7.2
(21.7), (21.3), (22.3), (23.9), (29.2),
544 368 201 91 41
(19.8), (21.9), (20.9), (21.9), (28.5),
PDa 197 178 122 62 25
−5.8 (21.1), 147 −3.0 (19.8), 46 3.9 (24.3), 18 6.8 (12.2), 4 5.5 (15.7), 4
a
N for PR, SD, and PD =/ All pts as radiographic response is only available for a subset of pts at wk 9; after wk 9 many PD pts discontinue per protocol. MID: LCSS ASBI = 10, EQ-5D VAS = 7.
Myers Squibb, Novartis, Pfizer, and ISIS. J. McDonald owns stock in Arena Pharma and Elan Pharma. C. Reynolds owns stock in Gilead. Advisory Board: J. Chandler (Bristol-Myers Squibb, ONYX, and Alexion). C. Reynolds (Eli Lilly, Bristol-Myers Squibb, Boehringer-Ingelheim, and Genentech). E. Stepanski (Bristol-Myers Squibb). G. Keogh (Dendrion). E. Stepanski has participated in advisory boards/been a consultant for Bristol-Myers Squibb. G. Keogh has participated in advisory boards for Dendrion. Board of Directors: N/A. Corporate-sponsored Research: E. Garon’s institution (Bristol-Myers Squibb, Merck, Pfizer, AstraZeneca, Eli Lilly, Novartis, and Genentech). G. Keogh (Pfizer, Medivation, BristolMyers Squibb, Dendrion, Merck, and Gilead). J. Schneider’s institution (Bristol-Myers Squibb and AstraZeneca). Other Substantive Relationships: J. Chandler has received compensation for travel, accommodations, and expenses from Caris. C. Reynolds has received honoraria from Eli Lilly, Bristol-Myers Squibb, Boehringer-Ingelheim, and Genentech. has participated in speakers’ bureaus on behalf of Eli Lilly, BoehringerIngelheim, and Genentech, and has received compensation for travel, accommodations, and expenses from Eli Lilly, Bristol-Myers Squibb, Boehringer-Ingelheim, and Genentech. E. Stepanski is an employee and stockholder at Vector Oncology. he has received compensation for travel, accommodations, and expenses from Bristol-Myers Squibb. B. Korytowski and X. Li are Bristol-Myers Squibb employees and stockholders. R. Sen, C. Coon, and J. McDonald are employees of Adelphi Values, which was paid by Bristol-Myers Squibb in connection with this study.
3090 POSTER Avelumab (MSB0010718C), an anti-PD-L1 antibody, in patients with metastatic or recurrent non-small-cell lung cancer progressing after platinum-based chemotherapy: A phase Ib trial J.L. Gulley1 , A. Rajan2 , D.R. Spigel3 , N. Iannotti4 , J. Chandler5 , D.J.L. Wong6 , J.L. Leach7 , W.J. Edenfield8 , D. Wang9 , M. Bajars10 , A. Von Heydebreck11 , K. Kelly12 . 1 Genitourinary Malignancy Branch, National Cancer Institute, National Institutes of Health, Laboratory of Tumor Immunology and Biology, Center for Cancer Research, Bethesda, MD, USA; 2 Center for Cancer Research, National Cancer Institute, Thoracic and Gastrointestinal Oncology Branch, Bethesda, MD, USA; 3 Sarah Cannon Research Institute, Tennessee Oncology, LLC, North Nashville, TN, USA; 4 Hematology Oncology Associates of The Treasure Coast, Hematology/Oncology, Port St. Lucie, FL, USA; 5 West Clinic, PC, Hematology/Oncology, Memphis, TN, USA; 6 UCLA Medical Center, Division of Hematology-Oncology, Los Angeles, CA, USA; 7 Virginia Piper Cancer Institute, Department of Hematology/Oncology, Minneapolis; 8 Institute for Translational Oncology Research, Hematology/Oncology, Greenville, SC, USA; 9 Henry Ford Hospital, Hematology/Oncology, Detroit, MI, USA; 10 EMD Serono, ImmunoOncology, Billerica, MA, USA; 11 Merck Serono, R&D Global Biostatistics, Darmstadt, Germany; 12 UC Davis Comprehensive Cancer Center, Hematology/Oncology, Sacramento, CA, USA; 13 Virginia Piper CancerInstitute, department of Hematology/OncologyMinneapolis, USA Background: The programmed death-1 receptor (PD-1) and its ligand (PD-L1) are key therapeutic targets in the reactivation of the immune response against cancer. Avelumab* (MSB0010718C) is a fully human anti-PD-L1 IgG1 antibody being investigated in clinical trials. We report clinical activity associated with tumour histology and PD-L1 expression in patients (pts) with advanced NSCLC progressing after platinum-based chemotherapy (NCT01772004). Materials and Methods: Pts were treated with avelumab at 10 mg/kg Q2W until confirmed progression, unacceptable toxicity, or any criterion for withdrawal occurred. Tumours were assessed every 6 wks (RECIST 1.1). Unconfirmed best overall response (BOR), progression-free survival (PFS), and overall survival (OS) were evaluated. Subgroup analyses based on histology and tumour PD-L1 expression at baseline as assessed by immunohistochemistry were performed.
Results: 184 pts with metastatic or recurrent NSCLC progressing after platinum-based doublet chemotherapy were treated with avelumab at 10 mg/kg as a 1-h infusion Q2W and had 6 mo follow-up. Median treatment duration was 12.2 wks (range 2−64). Median age was 65 y (range 31−83) and ECOG performance status was 0 [29.9%], 1 [69.6%], or >1 [0.5%]. Histology was adenocarcinoma (62%), squamous cell carcinoma (29%), or other (9%). Tumours were PD-L1+ in 86% of evaluable pts (n = 142; 1% tumour expression cutoff). Treatment-related treatmentemergent AEs (TEAEs; all grades) occurring >10% were fatigue (25.0%), infusion-related reaction (IRR; 20.7%), and nausea (13.0%). Treatmentrelated grade 3 TEAEs occurred in 23 pts (12.5%), including 4 grade 3/4 IRRs and 2 grade 5 events (radiation pneumonitis, acute respiratory failure). Objective responses were observed in 25 (13.6%) pts (95% CI: 9.0, 19.4), with 1 CR and 24 PRs; 19 responses were ongoing at data cutoff. Responses were reported in all histologies: adenocarcinoma (13 pts; ORR, 11.4% [95% CI: 6.2, 18.7]), squamous cell (7 pts; 13.2% [5.5, 25.3]), and other (5 pts; 29.4% [10.3, 56.0]). Stable disease was observed in 68 pts (37.0%). Median PFS was 11.6 wks (95% CI: 8.4, 13.7) and the PFS rate at 48 wks was 18.1% (95% CI: 12.0, 25.2). Median OS was 8.4 mo. The ORR in PD-L1+ pts (n = 122) was 15.6% (95% CI: 9.6, 23.2) and 10.0% (95% CI: 1.2, 31.7) in PD-L1− pts (n = 20). Median PFS in PD-L1+ pts was 12.0 wks vs 5.9 wks in PD-L1− pts. Median OS for the PD-L1+ population was 8.9 mo (95% CI: 8.0, ne) and 4.6 mo (95% CI: 2.76, ne) for PD-L1− pts. Conclusions: Avelumab showed a manageable safety profile and preliminary clinical activity in pts with advanced NSCLC independent of tumour histology. Tumour expression of PD-L1 was associated with a higher ORR and longer median PFS compared with PD-L1− tumours (using the 1% tumour expression cutoff). Randomized phase III trials of avelumab in 1L and 2L NSCLC are planned. *Proposed INN. Conflict of interest: Other Substantive Relationships: Honoraria: TRM Oncology.
3091 POSTER Characterization of advanced NSCLC patients with prolonged benefit after veliparib plus carboplatin/paclitaxel: Phase 2 results E. Juhasz1 , S. Ramalingam2 , N. Blais3 , J. Mazieres4 , M. Reck5 , M. Jones6 , L. Urban7 , S. Orlov8 , F. Barlesi9 , E. Kio10 , U. Keilholz11 , J. Qian12 , Q. Qin12 , P. Ansell12 , J. Dziubinski12 , C. Nickner12 , M. McKee12 , V. Giranda12 , ´ ´ ´ Pulmonologiai Intezet, ´ V. Gorbunova13 . 1 Orszagos Koranvi Intezet, TBC es Budapest, Hungary; 2 Winship Cancer Institute, Emory University Hospital, 4 3 ˆ Atlanta, USA; CHUM, Hopital Notre-Dame, Montreal, Canada; Larrey Hospital, CHU, Toulouse, France; 5 LungenClinic Grosshansdorf, Airway Research Center North, Grosshansdorf, Germany; 6 The Jones Clinic, ´ ´ ´ ´ ´ Oncology, New Albany, USA; 7 Matra Gyogyint ezet, Oncology, Matrah aza, Hungary; 8 Pavlov Medical University, Oncology, St. Petersburg, Russian ˆ Federation; 9 Aix Marseille University, Assistance Publique Hopitaux de Marseille, Marseille, France; 10 Indiana University Health, Goshen 11 Center for Cancer Care, Goshen, USA; Charite´ Comprehensive ´ Berlin, Germany; 12 AbbVie, Inc., North Chicago, Cancer Center, Charite, USA; 13 Institution of Russian Academy of Medical Science, Russian Oncological Research Center, St Petersburg, Russian Federation Background: Platinum-based regimens are the current standard of care for patients (pts) with metastatic non-small cell lung cancer (NSCLC). Veliparib (V) is a PARP inhibitor that augments platinum-induced DNA damage in preclinical studies. A recent Ph 2 trial of advanced NSCLC (M10–898) showed a trend to improved survival (HR 0.80; CI 0.54–1.18) when V was added to carboplatin (C) and paclitaxel (P). Here we examine characteristics of the group with the longest progression-free interval after VCP treatment. Methods: Patients with previously untreated advanced/metastatic NSCLC were randomized 2:1 to CP with either V at 120 mg BID or placebo (prespecified stratification by histology and smoking history) for up to 18 weeks.
S630
Abstracts
VCP-treated patients without evidence of progression after 36 weeks were considered to have prolonged benefit. Results: 158 patients were randomized. Of 105 VCP-treated patients, 14 had prolonged benefit (VPB) and 91 did not (VnPB). Eastern region was more common for VPB vs. VnPB (86%/57%). Other patient characteristics (age, gender, histology, smoking status, locally advanced, ECOG PS, subsequent therapy) were similar between groups. Serious adverse events (AE; 0%/31%), AE leading to V discontinuation (0%/23%), or to C discontinuation (0%/23%), or to P discontinuation (0%/26%) were more common in VnPB. AE and Grade 3/4 AE were similar between groups. Efficacy outcomes are summarized in the table. Table: Efficacy by response subgroup Response subgroup Progression-free survival months: median (95% CI) events: n (%) Overall survival months: median (95% CI) events: n (%) Overall response rate: % (95% CI) Duration of response, months: median (95% CI) ongoing responses: n (%) Best change in tumor size: median (range)
VPB (n = 14)
VnPB (n = 91)
NR* 2 (14%)
4.4 (3.2−5.8) 44 (48%)
NR* 4 (29%) 79 (49−95) NR* 9/11 (82%) −49.6 (−80.6 to −11.3)
9.9 (8.0–12.5) 70 (77%) 25 (17−36) 5.0 (4.4−7.0) 14/23 (61%) −16.1 (−94.3 to 14.8)
*NR, Not reached at median follow up (20 months).
Conclusions: Prolonged progression-free interval after VCP was associated with increased survival, reduction in tumor size, high response rate, and lasting response. Pts with prolonged benefit had fewer SAE and AEs requiring cessation of therapy. Tumor gene sequences are under analysis for genomic differences between groups. The clinical benefit of veliparib in NSCLC will be further assessed in ongoing Phase 3 trials (M11–089 and M14–359). Conflict of interest: Ownership: Qin Q, Qian J, Dziubinski J, Nickner C, Ansell P, McKee M, Giranda V are AbbVie stock owners. Other Substantive Relationships: Qin Q, Qian J, Dziubinski J, Nickner C, Ansell P, McKee M, Giranda V are AbbVie employees. Ramalingam S has served as a consultant on scientific advisory board meetings for AbbVie and has received honoraria. Reck M has served as a consultant and has received honoraria from Hoffmann-La Roche, Lilly, Boehringer-Ingelheim, Pfizer, AstraZeneca, BMS, MSD, and Novartis. 3092 POSTER Systemic immune-inflammation index (SII) in patients with advanced non-small cell lung cancer (nsclc) B. Rossana1 , S. Rinaldi1 , M. Santoni1 , T. Newsom-Davis2 , M. Tiberi3 , F. Morgese1 , M. Caramanti1 , A. Savini1 , M. Torniai1 , I. Fiordoliva1 , V. Paolucci1 , M. Bower2 , S. Cascinu1 . 1 Universita` Politecnica delle Marche, Dipartimento di Scienze Cliniche Molecolari Via Tronto 60126 Ancona, Ancona, Italy; 2 Chelsea & Westminster Hospital, ONCOLOGY − 369 Fulham Road, London SW10 9NH, United Kingdom; 3 Universita` Politecnica delle Marche, Chirurgia Toracica, Ancona, Italy Background: We aimed to assess the prognostic role of Systemic ImmuneInflammation Index (SII), obtained by analyzing the neutrophil, lymphocyte, and platelet counts, and to design prognostic models for patients receiving first-line chemo- or targeted therapy for advanced non-small cell lung cancer (NSCLC). Materials and Methods: Patients with advanced NSCLC were treated with first line chemo- or targeted therapy till March 2015 at our Institution. Patients were stratified in two groups with SII 1270 (Group A) vs <1270 (Group B). Progression free survival (PFS) and overall survival (OS) were estimated using Kaplan–Meier method. The best SII cutoff was identified by X-tiles program. A Cox regression model was carried out for univariate and multivariate analyses. Results: 311 patients were included in this analysis. At baseline, 179 patients had SII1270 (Group A), whilst 132 had lower SII (Group B). The median OS was 12.4 months in Group A and 21.7 months in Group B (p < 0.001), whilst the median PFS was 3.3 months and 5.2 months, respectively (p = 0.029). At multivariate analysis, ECOG-PS2, IV tumor stage and SII >1270 were predictors of worst OS. On the other hand, only wild-type EGFR status and SII1270 were independent prognostic factors for worst PFS. For OS, patients were stratified according to the absence of the 3 significant prognostic factors (13%), presence of 1 (44%), 2 (40%) and 3 factors (4%). In the 4 groups, the median OS was 47.0, 19.4, 10.2 and 4.0 months, respectively (p < 0.001). Similarly, patients were stratified for PFS based on the presence of 0, 1 or 2 factors. The median PFS was 8.7 months, 5.8 months and 3.3 months, respectively (p < 0.001). Conclusions: Pre-treatment SII is an independent prognostic factor for patients with advanced NSCLC treated with first-line therapies. These
prognostic models should be investigated and validated in prospective studies. No conflict of interest. 3093 POSTER Veliparib with carboplatin and paclitaxel: factors predictive of favorable outcomes in NSCLC M. Reck1 , S. Ramalingam2 , N. Blais3 , J. Mazieres4 , M. Jones5 , E. Juhasz6 , L. Urban7 , S. Orlov8 , F. Barlesi9 , E. Kio10 , U. Keilholz11 , J. Qian12 , Q. Qin12 , J. Dziubinski12 , C. Nickner12 , P. Ansell12 , M. McKee12 , V. Giranda12 , V. Gorbunova13 . 1 LungenClinic Grosshansdorf, Airway Research Center North, Grosshansdorf, Germany; 2 Winship Cancer ˆ Institute, Emory University Hospital, Atlanta, USA; 3 CHUM, Hopital Notre-Dame, Montreal, Canada; 4 Larrey Hospital, CHU, Toulouse, France; 5 6 ´ The Jones Clinic, Oncology, New Albany, USA; Orszagos Koranyi, ´ Pulmonologiai Intezet, ´ ´ ´ ´ TBC es Budapest, Hungary; 7 Matra Gyogyint ezet, 8 ´ ´ Oncology, Matrah aza, Hungary; Pavlov Medical University, Oncology, 9 St. Petersburg, Russian Federation; Aix Marseille University, Assistance ˆ Publique Hopitaux de Marseille, Marseille, France; 10 Indiana University Health, Goshen Center for Cancer Care, Goshen, USA; 11 Charite´ ´ Berlin, Germany; 12 AbbVie, Inc., Comprehensive Cancer Center, Charite, North Chicago, USA; 13 Institution of Russian Academy of Medical Science, Russian Oncological Research Center, St Petersburg, Russian Federation Background: Platinum-based regimens are standard of care for metastatic non-small cell lung cancer (NSCLC). Veliparib (V) is a PARP inhibitor that augments platinum-induced DNA damage in preclinical studies. A Ph 2 trial of advanced NSCLC showed a trend toward improved survival (HR 0.80; CI 0.54–1.18) when V was added to carboplatin (C) and paclitaxel (P). The objective of this analysis is to identify factors predictive of favorable outcomes with VCP in the trial. Methods: Patients (pts) with previously untreated advanced/metastatic NSCLC were randomized 2:1 to CP with either V at 120 mg BID or placebo (randomization stratified by histology and smoking history). The association of treatment and baseline characteristics with outcomes was assessed using univariate and multivariate proportional hazard models. Covariates included smoking status (current, former, never), histology (squamous, nonsquamous), age (<65, 65), ECOG (0, 1), gender (female, male), and geographic region (West Europe/Americas, East Europe/Russia). Test for interaction was performed within the multivariate model. Results: Univariate factors associated with improved PFS or OS (p < 0.10) with VCP were current smoking, male gender, age <65, ECOG grade 1, eastern region, and squamous histology (Table). A multivariate analysis including all factors identified smoking status as the single most predictive factor for improved PFS (VCP/CP HR 0.409, p = 0.040) and OS (VCP/CP HR 0.454, p = 0.038). Table: Efficacy (univariate model) Subgroup (N for VCP, CP)
Current smoker (64, 31) Male gender (75, 32) Age <65 years (62, 30) ECOG = 1 (70, 36) Eastern region (64, 31) Squamous histology (51, 25)
PFS VCP/CP HR (95% CI) 0.39 (0. 22−0. 68) 0. 48 (0. 28−0. 83) 0. 51 (0. 29−0. 90) 0. 61 (0. 36−1. 03) 0. 58 (0. 32–1.07) 0. 52 (0. 25–1.10)
p-value 0.0009 0.0082 0.0203 0.064 0.0794 0.0862
OS VCP/CP HR (95% CI) 0. 44 (0. 27−0. 72) 0. 67 (0. 42−1. 07) 0. 71 (0.43– 1.16) 0.69 (0.44– 1.07) 0.75 (0.46– 1.24) 0.73 (0.43– 1.25)
p-value 0. 001 0. 0912 0. 2492 0.0994 0.2696 0.2492
Conclusions: Multivariate modeling suggests that current smoking is strongly associated with improved outcome with veliparib, and other univariate associations may be due to smoking in pts with those characteristics. Smoking status should be a stratification or selection factor in future studies of veliparib for NSCLC. Analysis of current smokers is planned for the Ph 3 veliparib studies of non-squamous (M14–359) and squamous (M11–089) NSCLC. Conflict of interest: Ownership: Qin Q, Qian J, Dziubinsk J, Nickner C, Ansell P, McKee M, Giranda V are AbbVie stock owners. Other Substantive Relationships: Qin Q, Qian J, Dziubinsk J, Nickner C, Ansell P, McKee M, Giranda V are AbbVie employees. Ramalingam S has served as a consultant on scientific advisory board meetings for AbbVie and has received honoraria. Reck M has served as a consultant and has received honoraria from Hoffmann-La Roche, Lilly, Boehringer-Ingelheim, Pfizer, AstraZeneca, BMS, MSD, and Novartis.
S629
Table (abstract 3089). Wk
6 12 18 24 30
Mean change (standard deviation), n LCSS ASBI All pts PRa
SDa
0.6 (14.2), 557 −1.8 (14.9), 375 −2.5 (13.3), 205 −3.9 (13.7), 95 −2.8 (14.4), 46
−0.7 −2.0 −3.8 −2.8 −3.0
−2.3 −2.4 −1.3 −9.4 −4.2
(12.0), (13.7), (13.8), (12.2), (13.5),
52 53 40 22 12
(13.6), (14.5), (13.4), (14.2), (15.2),
207 183 125 64 28
PDa
EQ-5D VAS All pts
PRa
SDa
2.5 (15.0), 148 −1.0 (16.2), 45 −0.9 (10.3), 18 5.0 (12.4), 4 7.2 (12.0), 4
1.0 5.8 8.2 8.2 8.4
7.3 (22.4), 52 6.6 (24.7), 52 8.1 (27.6), 39 18.1 (31.0), 20 13.7 (38.2), 10
3.8 6.4 8.2 5.2 7.2
(21.7), (21.3), (22.3), (23.9), (29.2),
544 368 201 91 41
(19.8), (21.9), (20.9), (21.9), (28.5),
PDa 197 178 122 62 25
−5.8 (21.1), 147 −3.0 (19.8), 46 3.9 (24.3), 18 6.8 (12.2), 4 5.5 (15.7), 4
a
N for PR, SD, and PD =/ All pts as radiographic response is only available for a subset of pts at wk 9; after wk 9 many PD pts discontinue per protocol. MID: LCSS ASBI = 10, EQ-5D VAS = 7.
Myers Squibb, Novartis, Pfizer, and ISIS. J. McDonald owns stock in Arena Pharma and Elan Pharma. C. Reynolds owns stock in Gilead. Advisory Board: J. Chandler (Bristol-Myers Squibb, ONYX, and Alexion). C. Reynolds (Eli Lilly, Bristol-Myers Squibb, Boehringer-Ingelheim, and Genentech). E. Stepanski (Bristol-Myers Squibb). G. Keogh (Dendrion). E. Stepanski has participated in advisory boards/been a consultant for Bristol-Myers Squibb. G. Keogh has participated in advisory boards for Dendrion. Board of Directors: N/A. Corporate-sponsored Research: E. Garon’s institution (Bristol-Myers Squibb, Merck, Pfizer, AstraZeneca, Eli Lilly, Novartis, and Genentech). G. Keogh (Pfizer, Medivation, BristolMyers Squibb, Dendrion, Merck, and Gilead). J. Schneider’s institution (Bristol-Myers Squibb and AstraZeneca). Other Substantive Relationships: J. Chandler has received compensation for travel, accommodations, and expenses from Caris. C. Reynolds has received honoraria from Eli Lilly, Bristol-Myers Squibb, Boehringer-Ingelheim, and Genentech. has participated in speakers’ bureaus on behalf of Eli Lilly, BoehringerIngelheim, and Genentech, and has received compensation for travel, accommodations, and expenses from Eli Lilly, Bristol-Myers Squibb, Boehringer-Ingelheim, and Genentech. E. Stepanski is an employee and stockholder at Vector Oncology. he has received compensation for travel, accommodations, and expenses from Bristol-Myers Squibb. B. Korytowski and X. Li are Bristol-Myers Squibb employees and stockholders. R. Sen, C. Coon, and J. McDonald are employees of Adelphi Values, which was paid by Bristol-Myers Squibb in connection with this study.
3090 POSTER Avelumab (MSB0010718C), an anti-PD-L1 antibody, in patients with metastatic or recurrent non-small-cell lung cancer progressing after platinum-based chemotherapy: A phase Ib trial J.L. Gulley1 , A. Rajan2 , D.R. Spigel3 , N. Iannotti4 , J. Chandler5 , D.J.L. Wong6 , J.L. Leach7 , W.J. Edenfield8 , D. Wang9 , M. Bajars10 , A. Von Heydebreck11 , K. Kelly12 . 1 Genitourinary Malignancy Branch, National Cancer Institute, National Institutes of Health, Laboratory of Tumor Immunology and Biology, Center for Cancer Research, Bethesda, MD, USA; 2 Center for Cancer Research, National Cancer Institute, Thoracic and Gastrointestinal Oncology Branch, Bethesda, MD, USA; 3 Sarah Cannon Research Institute, Tennessee Oncology, LLC, North Nashville, TN, USA; 4 Hematology Oncology Associates of The Treasure Coast, Hematology/Oncology, Port St. Lucie, FL, USA; 5 West Clinic, PC, Hematology/Oncology, Memphis, TN, USA; 6 UCLA Medical Center, Division of Hematology-Oncology, Los Angeles, CA, USA; 7 Virginia Piper Cancer Institute, Department of Hematology/Oncology, Minneapolis; 8 Institute for Translational Oncology Research, Hematology/Oncology, Greenville, SC, USA; 9 Henry Ford Hospital, Hematology/Oncology, Detroit, MI, USA; 10 EMD Serono, ImmunoOncology, Billerica, MA, USA; 11 Merck Serono, R&D Global Biostatistics, Darmstadt, Germany; 12 UC Davis Comprehensive Cancer Center, Hematology/Oncology, Sacramento, CA, USA; 13 Virginia Piper CancerInstitute, department of Hematology/OncologyMinneapolis, USA Background: The programmed death-1 receptor (PD-1) and its ligand (PD-L1) are key therapeutic targets in the reactivation of the immune response against cancer. Avelumab* (MSB0010718C) is a fully human anti-PD-L1 IgG1 antibody being investigated in clinical trials. We report clinical activity associated with tumour histology and PD-L1 expression in patients (pts) with advanced NSCLC progressing after platinum-based chemotherapy (NCT01772004). Materials and Methods: Pts were treated with avelumab at 10 mg/kg Q2W until confirmed progression, unacceptable toxicity, or any criterion for withdrawal occurred. Tumours were assessed every 6 wks (RECIST 1.1). Unconfirmed best overall response (BOR), progression-free survival (PFS), and overall survival (OS) were evaluated. Subgroup analyses based on histology and tumour PD-L1 expression at baseline as assessed by immunohistochemistry were performed.
Results: 184 pts with metastatic or recurrent NSCLC progressing after platinum-based doublet chemotherapy were treated with avelumab at 10 mg/kg as a 1-h infusion Q2W and had 6 mo follow-up. Median treatment duration was 12.2 wks (range 2−64). Median age was 65 y (range 31−83) and ECOG performance status was 0 [29.9%], 1 [69.6%], or >1 [0.5%]. Histology was adenocarcinoma (62%), squamous cell carcinoma (29%), or other (9%). Tumours were PD-L1+ in 86% of evaluable pts (n = 142; 1% tumour expression cutoff). Treatment-related treatmentemergent AEs (TEAEs; all grades) occurring >10% were fatigue (25.0%), infusion-related reaction (IRR; 20.7%), and nausea (13.0%). Treatmentrelated grade 3 TEAEs occurred in 23 pts (12.5%), including 4 grade 3/4 IRRs and 2 grade 5 events (radiation pneumonitis, acute respiratory failure). Objective responses were observed in 25 (13.6%) pts (95% CI: 9.0, 19.4), with 1 CR and 24 PRs; 19 responses were ongoing at data cutoff. Responses were reported in all histologies: adenocarcinoma (13 pts; ORR, 11.4% [95% CI: 6.2, 18.7]), squamous cell (7 pts; 13.2% [5.5, 25.3]), and other (5 pts; 29.4% [10.3, 56.0]). Stable disease was observed in 68 pts (37.0%). Median PFS was 11.6 wks (95% CI: 8.4, 13.7) and the PFS rate at 48 wks was 18.1% (95% CI: 12.0, 25.2). Median OS was 8.4 mo. The ORR in PD-L1+ pts (n = 122) was 15.6% (95% CI: 9.6, 23.2) and 10.0% (95% CI: 1.2, 31.7) in PD-L1− pts (n = 20). Median PFS in PD-L1+ pts was 12.0 wks vs 5.9 wks in PD-L1− pts. Median OS for the PD-L1+ population was 8.9 mo (95% CI: 8.0, ne) and 4.6 mo (95% CI: 2.76, ne) for PD-L1− pts. Conclusions: Avelumab showed a manageable safety profile and preliminary clinical activity in pts with advanced NSCLC independent of tumour histology. Tumour expression of PD-L1 was associated with a higher ORR and longer median PFS compared with PD-L1− tumours (using the 1% tumour expression cutoff). Randomized phase III trials of avelumab in 1L and 2L NSCLC are planned. *Proposed INN. Conflict of interest: Other Substantive Relationships: Honoraria: TRM Oncology.
3091 POSTER Characterization of advanced NSCLC patients with prolonged benefit after veliparib plus carboplatin/paclitaxel: Phase 2 results E. Juhasz1 , S. Ramalingam2 , N. Blais3 , J. Mazieres4 , M. Reck5 , M. Jones6 , L. Urban7 , S. Orlov8 , F. Barlesi9 , E. Kio10 , U. Keilholz11 , J. Qian12 , Q. Qin12 , P. Ansell12 , J. Dziubinski12 , C. Nickner12 , M. McKee12 , V. Giranda12 , ´ ´ ´ Pulmonologiai Intezet, ´ V. Gorbunova13 . 1 Orszagos Koranvi Intezet, TBC es Budapest, Hungary; 2 Winship Cancer Institute, Emory University Hospital, 4 3 ˆ Atlanta, USA; CHUM, Hopital Notre-Dame, Montreal, Canada; Larrey Hospital, CHU, Toulouse, France; 5 LungenClinic Grosshansdorf, Airway Research Center North, Grosshansdorf, Germany; 6 The Jones Clinic, ´ ´ ´ ´ ´ Oncology, New Albany, USA; 7 Matra Gyogyint ezet, Oncology, Matrah aza, Hungary; 8 Pavlov Medical University, Oncology, St. Petersburg, Russian ˆ Federation; 9 Aix Marseille University, Assistance Publique Hopitaux de Marseille, Marseille, France; 10 Indiana University Health, Goshen 11 Center for Cancer Care, Goshen, USA; Charite´ Comprehensive ´ Berlin, Germany; 12 AbbVie, Inc., North Chicago, Cancer Center, Charite, USA; 13 Institution of Russian Academy of Medical Science, Russian Oncological Research Center, St Petersburg, Russian Federation Background: Platinum-based regimens are the current standard of care for patients (pts) with metastatic non-small cell lung cancer (NSCLC). Veliparib (V) is a PARP inhibitor that augments platinum-induced DNA damage in preclinical studies. A recent Ph 2 trial of advanced NSCLC (M10–898) showed a trend to improved survival (HR 0.80; CI 0.54–1.18) when V was added to carboplatin (C) and paclitaxel (P). Here we examine characteristics of the group with the longest progression-free interval after VCP treatment. Methods: Patients with previously untreated advanced/metastatic NSCLC were randomized 2:1 to CP with either V at 120 mg BID or placebo (prespecified stratification by histology and smoking history) for up to 18 weeks.
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Abstracts
VCP-treated patients without evidence of progression after 36 weeks were considered to have prolonged benefit. Results: 158 patients were randomized. Of 105 VCP-treated patients, 14 had prolonged benefit (VPB) and 91 did not (VnPB). Eastern region was more common for VPB vs. VnPB (86%/57%). Other patient characteristics (age, gender, histology, smoking status, locally advanced, ECOG PS, subsequent therapy) were similar between groups. Serious adverse events (AE; 0%/31%), AE leading to V discontinuation (0%/23%), or to C discontinuation (0%/23%), or to P discontinuation (0%/26%) were more common in VnPB. AE and Grade 3/4 AE were similar between groups. Efficacy outcomes are summarized in the table. Table: Efficacy by response subgroup Response subgroup Progression-free survival months: median (95% CI) events: n (%) Overall survival months: median (95% CI) events: n (%) Overall response rate: % (95% CI) Duration of response, months: median (95% CI) ongoing responses: n (%) Best change in tumor size: median (range)
VPB (n = 14)
VnPB (n = 91)
NR* 2 (14%)
4.4 (3.2−5.8) 44 (48%)
NR* 4 (29%) 79 (49−95) NR* 9/11 (82%) −49.6 (−80.6 to −11.3)
9.9 (8.0–12.5) 70 (77%) 25 (17−36) 5.0 (4.4−7.0) 14/23 (61%) −16.1 (−94.3 to 14.8)
*NR, Not reached at median follow up (20 months).
Conclusions: Prolonged progression-free interval after VCP was associated with increased survival, reduction in tumor size, high response rate, and lasting response. Pts with prolonged benefit had fewer SAE and AEs requiring cessation of therapy. Tumor gene sequences are under analysis for genomic differences between groups. The clinical benefit of veliparib in NSCLC will be further assessed in ongoing Phase 3 trials (M11–089 and M14–359). Conflict of interest: Ownership: Qin Q, Qian J, Dziubinski J, Nickner C, Ansell P, McKee M, Giranda V are AbbVie stock owners. Other Substantive Relationships: Qin Q, Qian J, Dziubinski J, Nickner C, Ansell P, McKee M, Giranda V are AbbVie employees. Ramalingam S has served as a consultant on scientific advisory board meetings for AbbVie and has received honoraria. Reck M has served as a consultant and has received honoraria from Hoffmann-La Roche, Lilly, Boehringer-Ingelheim, Pfizer, AstraZeneca, BMS, MSD, and Novartis. 3092 POSTER Systemic immune-inflammation index (SII) in patients with advanced non-small cell lung cancer (nsclc) B. Rossana1 , S. Rinaldi1 , M. Santoni1 , T. Newsom-Davis2 , M. Tiberi3 , F. Morgese1 , M. Caramanti1 , A. Savini1 , M. Torniai1 , I. Fiordoliva1 , V. Paolucci1 , M. Bower2 , S. Cascinu1 . 1 Universita` Politecnica delle Marche, Dipartimento di Scienze Cliniche Molecolari Via Tronto 60126 Ancona, Ancona, Italy; 2 Chelsea & Westminster Hospital, ONCOLOGY − 369 Fulham Road, London SW10 9NH, United Kingdom; 3 Universita` Politecnica delle Marche, Chirurgia Toracica, Ancona, Italy Background: We aimed to assess the prognostic role of Systemic ImmuneInflammation Index (SII), obtained by analyzing the neutrophil, lymphocyte, and platelet counts, and to design prognostic models for patients receiving first-line chemo- or targeted therapy for advanced non-small cell lung cancer (NSCLC). Materials and Methods: Patients with advanced NSCLC were treated with first line chemo- or targeted therapy till March 2015 at our Institution. Patients were stratified in two groups with SII 1270 (Group A) vs <1270 (Group B). Progression free survival (PFS) and overall survival (OS) were estimated using Kaplan–Meier method. The best SII cutoff was identified by X-tiles program. A Cox regression model was carried out for univariate and multivariate analyses. Results: 311 patients were included in this analysis. At baseline, 179 patients had SII1270 (Group A), whilst 132 had lower SII (Group B). The median OS was 12.4 months in Group A and 21.7 months in Group B (p < 0.001), whilst the median PFS was 3.3 months and 5.2 months, respectively (p = 0.029). At multivariate analysis, ECOG-PS2, IV tumor stage and SII >1270 were predictors of worst OS. On the other hand, only wild-type EGFR status and SII1270 were independent prognostic factors for worst PFS. For OS, patients were stratified according to the absence of the 3 significant prognostic factors (13%), presence of 1 (44%), 2 (40%) and 3 factors (4%). In the 4 groups, the median OS was 47.0, 19.4, 10.2 and 4.0 months, respectively (p < 0.001). Similarly, patients were stratified for PFS based on the presence of 0, 1 or 2 factors. The median PFS was 8.7 months, 5.8 months and 3.3 months, respectively (p < 0.001). Conclusions: Pre-treatment SII is an independent prognostic factor for patients with advanced NSCLC treated with first-line therapies. These
prognostic models should be investigated and validated in prospective studies. No conflict of interest. 3093 POSTER Veliparib with carboplatin and paclitaxel: factors predictive of favorable outcomes in NSCLC M. Reck1 , S. Ramalingam2 , N. Blais3 , J. Mazieres4 , M. Jones5 , E. Juhasz6 , L. Urban7 , S. Orlov8 , F. Barlesi9 , E. Kio10 , U. Keilholz11 , J. Qian12 , Q. Qin12 , J. Dziubinski12 , C. Nickner12 , P. Ansell12 , M. McKee12 , V. Giranda12 , V. Gorbunova13 . 1 LungenClinic Grosshansdorf, Airway Research Center North, Grosshansdorf, Germany; 2 Winship Cancer ˆ Institute, Emory University Hospital, Atlanta, USA; 3 CHUM, Hopital Notre-Dame, Montreal, Canada; 4 Larrey Hospital, CHU, Toulouse, France; 5 6 ´ The Jones Clinic, Oncology, New Albany, USA; Orszagos Koranyi, ´ Pulmonologiai Intezet, ´ ´ ´ ´ TBC es Budapest, Hungary; 7 Matra Gyogyint ezet, 8 ´ ´ Oncology, Matrah aza, Hungary; Pavlov Medical University, Oncology, 9 St. Petersburg, Russian Federation; Aix Marseille University, Assistance ˆ Publique Hopitaux de Marseille, Marseille, France; 10 Indiana University Health, Goshen Center for Cancer Care, Goshen, USA; 11 Charite´ ´ Berlin, Germany; 12 AbbVie, Inc., Comprehensive Cancer Center, Charite, North Chicago, USA; 13 Institution of Russian Academy of Medical Science, Russian Oncological Research Center, St Petersburg, Russian Federation Background: Platinum-based regimens are standard of care for metastatic non-small cell lung cancer (NSCLC). Veliparib (V) is a PARP inhibitor that augments platinum-induced DNA damage in preclinical studies. A Ph 2 trial of advanced NSCLC showed a trend toward improved survival (HR 0.80; CI 0.54–1.18) when V was added to carboplatin (C) and paclitaxel (P). The objective of this analysis is to identify factors predictive of favorable outcomes with VCP in the trial. Methods: Patients (pts) with previously untreated advanced/metastatic NSCLC were randomized 2:1 to CP with either V at 120 mg BID or placebo (randomization stratified by histology and smoking history). The association of treatment and baseline characteristics with outcomes was assessed using univariate and multivariate proportional hazard models. Covariates included smoking status (current, former, never), histology (squamous, nonsquamous), age (<65, 65), ECOG (0, 1), gender (female, male), and geographic region (West Europe/Americas, East Europe/Russia). Test for interaction was performed within the multivariate model. Results: Univariate factors associated with improved PFS or OS (p < 0.10) with VCP were current smoking, male gender, age <65, ECOG grade 1, eastern region, and squamous histology (Table). A multivariate analysis including all factors identified smoking status as the single most predictive factor for improved PFS (VCP/CP HR 0.409, p = 0.040) and OS (VCP/CP HR 0.454, p = 0.038). Table: Efficacy (univariate model) Subgroup (N for VCP, CP)
Current smoker (64, 31) Male gender (75, 32) Age <65 years (62, 30) ECOG = 1 (70, 36) Eastern region (64, 31) Squamous histology (51, 25)
PFS VCP/CP HR (95% CI) 0.39 (0. 22−0. 68) 0. 48 (0. 28−0. 83) 0. 51 (0. 29−0. 90) 0. 61 (0. 36−1. 03) 0. 58 (0. 32–1.07) 0. 52 (0. 25–1.10)
p-value 0.0009 0.0082 0.0203 0.064 0.0794 0.0862
OS VCP/CP HR (95% CI) 0. 44 (0. 27−0. 72) 0. 67 (0. 42−1. 07) 0. 71 (0.43– 1.16) 0.69 (0.44– 1.07) 0.75 (0.46– 1.24) 0.73 (0.43– 1.25)
p-value 0. 001 0. 0912 0. 2492 0.0994 0.2696 0.2492
Conclusions: Multivariate modeling suggests that current smoking is strongly associated with improved outcome with veliparib, and other univariate associations may be due to smoking in pts with those characteristics. Smoking status should be a stratification or selection factor in future studies of veliparib for NSCLC. Analysis of current smokers is planned for the Ph 3 veliparib studies of non-squamous (M14–359) and squamous (M11–089) NSCLC. Conflict of interest: Ownership: Qin Q, Qian J, Dziubinsk J, Nickner C, Ansell P, McKee M, Giranda V are AbbVie stock owners. Other Substantive Relationships: Qin Q, Qian J, Dziubinsk J, Nickner C, Ansell P, McKee M, Giranda V are AbbVie employees. Ramalingam S has served as a consultant on scientific advisory board meetings for AbbVie and has received honoraria. Reck M has served as a consultant and has received honoraria from Hoffmann-La Roche, Lilly, Boehringer-Ingelheim, Pfizer, AstraZeneca, BMS, MSD, and Novartis.