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Background Patients with metastatic pancreatic cancer often have a detriment in health-related quality of life (HRQoL). In the randomized, double-blind, phase III POLO trial progression-free survival was significantly longer with maintenance olaparib, a poly(ADP-ribose) polymerase inhibitor, than placebo in patients with a germline BRCA1 and/or BRCA2 mutation (gBRCAm) and metastatic pancreatic cancer whose disease had not progressed during first-line platinum-based chemotherapy. The prespecified HRQoL evaluation is reported here. Patients and methods Patients were randomized to receive maintenance olaparib (300 mg b.i.d.; tablets) or placebo. HRQoL was assessed using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30-item module at baseline, every 4 weeks until disease progression, at discontinuation, and 30 days after last dose. Scores ranged from 0 to 100; a ≥10-point change or difference between arms was considered clinically meaningful. Adjusted mean change from baseline was analysed using a mixed model for repeated measures. Time to sustained clinically meaningful deterioration (TSCMD) was analysed using a log-rank test. Results Of 154 randomized patients, 89 of 92 olaparib-arm and 58 of 62 placebo-arm patients were included in HRQoL analyses. The adjusted mean change in Global Health Status (GHS) score from baseline was <10 points in both arms and there was no significant between-group difference [−2.47; 95% confidence interval (CI) −7.27, 2.33; P  =   0.31]. Analysis of physical functioning scores showed a significant between-group difference (−4.45 points; 95% CI −8.75, −0.16; P  =   0.04). There was no difference in TSCMD for olaparib versus placebo for GHS [ P  =   0.25; hazard ratio (HR) 0.72; 95% CI 0.41, 1.27] or physical functioning (P  =   0.32; HR 1.38; 95% CI 0.73, 2.63). Conclusions HRQoL was preserved with maintenance olaparib treatment with no clinically meaningful difference compared with placebo. These results support the observed efficacy benefit of maintenance olaparib in patients with a gBRCAm and metastatic pancreatic cancer. ClincalTrials.gov number NCT02184195. [ABSTRACT FROM AUTHOR]

Background: This study evaluated tumor response to olaratumab (an anti-PDGFRa monoclonal antibody) in previously treated patients with metastatic gastrointestinal stromal tumor (GIST) with or without PDGFRa mutations (cohorts 1 and 2, respectively). Patients and methods: Patients received olaratumab 20 mg/kg intravenously every 14 days until disease progression, death, or intolerable toxicity occurred. Outcome measures were 12-week tumor response, progression-free survival (PFS), overall survival (OS), and safety. Results: Of 30 patients enrolled, 21 patients received≤1 dose of olaratumab. In the evaluable population (cohort 1, n=6; cohort 2, n=14), no complete response (CR) or partial response (PR) was observed. Stable disease (SD) was observed in 3 patients (50.0%) in cohort 1 and 2 patients (14.3%) in cohort 2. Progressive disease (PD) was observed in 3 patients (50.0%) in cohort 1 and 12 patients (85.7%) in cohort 2. The 12-week clinical benefit rate (CR+PR+SD) (90% CI) was 50.0% (15.3-84.7%) in cohort 1 and 14.3% (2.6-38.5%) in cohort 2. SD lasted beyond 12 weeks in 5 patients (cohort 1, n=3; cohort 2, n=2). Median PFS (90% CI) was 32.1 (5.0-35.9) weeks in cohort 1 and 6.1 (5.7-6.3) weeks in cohort 2. Median OS was not reached in cohort 1 and was 24.9 (14.4-49.1) weeks in cohort 2. All patients in cohort 1 and 9 (64.3%) in cohort 2 experienced an olaratumab-related adverse event (AE), most commonly fatigue (38.1%), nausea (19.0%), and peripheral edema (14.3%). Two grade≤3 olaratumab-related events were reported (cohort 1, syncope; cohort 2, hypertension). Conclusions: Olaratumab had an acceptable AE profile in patients with GIST. While there was no apparent effect on PFS in patients without PDGFRa mutations, patients with PDGFRα-mutant GIST (all with D842V mutations) treated with olaratumab had longer disease control compared with historical data for this genotype. [ABSTRACT FROM AUTHOR]

Purpose/Objective(s): • Platinum-based chemotherapy with pemetrexed is an appropriate first line treatment option for unresectable malignant pleural mesothelioma (MPM) • The DREAM¹ and PrE0505² Phase II trials combined durvalumab (PD-L1 inhibitor) with a platinum and pemetrexed both exceeding pre-specified response with acceptable toxicity • CheckMate 7433 recently reported an overall survival benefit with ipilimumab plus nivolumab vs. chemotherapy (HR 0.74, 95% CI 0.50 to 0.91). However, this benefit was less apparent in the 75% of patients with epithelioid histology (HR 0.86, 95% CI 0.69 to 1.08) • Clinical trials to further explore optimal first line treatment for MPM with immunotherapy are needed International, open label, randomised (2:1), multi-centre, phase 3 trial • 480 patients (320 durvalumab and chemotherapy, 160 chemotherapy) to be recruited over 27 months and followed for another 24 months • This provides over 85% power if the true hazard ratio for overall survival is 0.70 with 2-sided alpha of 0.05, assuming a median survival of 15 months in the chemotherapy group, 21.4 months in the durvalumab and chemotherapy group, with an allowance for crossover TBD TBD [ABSTRACT FROM AUTHOR]

Background We evaluated the efficacy and safety of ganitumab (a mAb antagonist of insulin-like growth factor 1 receptor) or conatumumab (a mAb agonist of human death receptor 5) combined with gemcitabine in a randomized phase 2 trial in patients with metastatic pancreatic cancer. Patients and methods Patients with a previously untreated metastatic pancreatic adenocarcinoma and an Eastern Cooperative Oncology Group (ECOG) performance status ≤1 were randomized 1 : 1 : 1 to i.v. gemcitabine 1000 mg/m2 (days 1, 8, and 15 of each 28-day cycle) combined with open-label ganitumab (12 mg/kg every 2 weeks [Q2W]), double-blind conatumumab (10 mg/kg Q2W), or double-blind placebo Q2W. The primary end point was 6-month survival rate. Results In total, 125 patients were randomized. The 6-month survival rates were 57% (95% CI 41–70) in the ganitumab arm, 59% (42–73) in the conatumumab arm, and 50% (33–64) in the placebo arm. The grade ≥3 adverse events in the ganitumab, conatumumab, and placebo arms, respectively, included neutropenia (18/22/13%), thrombocytopenia (15/17/8%), fatigue (13/12/5%), alanine aminotransferase increase (15/5/8%), and hyperglycemia (18/2/3%). Conclusions Ganitumab combined with gemcitabine had tolerable toxicity and showed trends toward an improved 6-month survival rate and overall survival. Additional investigation into this combination is warranted. Conatumumab combined with gemcitabine showed some evidence of activity as assessed by the 6-month survival rate. [ABSTRACT FROM AUTHOR]

Objectives: This study's aim was to examine whether treatment with pioglitazone, added to conventional lipid-lowering therapy, would improve myocardial glucose utilization (MGU) and blood flow (MBF) in nondiabetic patients with familial combined hyperlipidemia (FCHL).Background: Thiazolidinediones were found to improve insulin sensitivity and MGU in type 2 diabetes and MBF in Mexican Americans with insulin resistance. Familial combined hyperlipidemia is a complex genetic disorder conferring a high risk of premature coronary artery disease, characterized by high serum cholesterol and/or triglyceride, low high-density lipoprotein (HDL) cholesterol, and insulin resistance.Methods: We undertook a randomized, double-blind, placebo-controlled study in 26 patients with FCHL, treated with pioglitazone or matching placebo 30 mg daily for 4 weeks, followed by 45 mg daily for 12 weeks. Positron emission tomography was used to measure MBF at rest and during adenosine-induced hyperemia and MGU during euglycemic hyperinsulinemic clamp at baseline and after treatment.Results: Whereas no change was observed in the placebo group after treatment, patients receiving pioglitazone showed a significant increase in whole body glucose disposal (3.93 +/- 1.59 mg/kg/min to 5.24 +/- 1.65 mg/kg/min; p = 0.004) and MGU (0.62 +/- 0.26 micromol/g/min to 0.81 +/- 0.14 micromol/g/min; p = 0.0007), accompanied by a significant improvement in resting MBF (1.11 +/- 0.20 ml/min/g to 1.25 +/- 0.21 ml/min/g; p = 0.008). Furthermore, in the pioglitazone group HDL cholesterol (+28%; p = 0.003) and adiponectin (+156.2%; p = 0.0001) were increased and plasma insulin (-35%; p = 0.017) was reduced.Conclusions: In patients with FCHL treated with conventional lipid-lowering therapy, the addition of pioglitazone led to significant improvements in MGU and MBF, with a favorable effect on blood lipid and metabolic parameters. (A study to investigate the effect of pioglitazone on whole body and myocardial glucose uptake and myocardial blood flow/coronary vasodilator reserve in patients with familial combined hyperlipidaemia; http://www.controlled-trials.com/mrct/trial/230761/ISRCTN78563659; ISRCTN78563659). [ABSTRACT FROM AUTHOR]

Background CBP501, a synthetic duodecapeptide, increases cisplatin influx into tumor cells through an interaction with calmodulin enhancing cisplatin cytotoxicity, and effects cell cycle progression by abrogating DNA repair at the G2 checkpoint. In phase I clinical trials of CBP501 alone or in combination with cisplatin, the most common toxicity was infusion-related urticaria. Activity of CBP501 plus cisplatin was observed in patients with ovarian cancer and mesothelioma, including some patients previously treated with cisplatin. Methods Chemotherapy naïve patients with unresectable MPM were stratified by histology and performance status, and randomized 2:1 to pemetrexed/cisplatin plus CBP501 25 mg/m² IV (Arm A) or pemetrexed/cisplatin alone (Arm B). The primary endpoint was progression free survival (PFS) at 4 months. Results 65 patients were randomized, and 63 were treated. Patient characteristics in the two arms were balanced. Based on independent radiology review of the treated population, 25/40 patients (63%) in Arm A and 9/23 (39%) in Arm B had PFS ≥ 4 mo; the median PFS was 5.1 mo (95% CI, 3.9, 6.5) vs 3.4 mo (2.5, 6.7). Median OS was 13.3 mo (9.2, 16.3) in Arm A and 12.8 (6.5, 16.1) in Arm B. Adverse events were not different than expected from standard chemotherapy, and comparable in the two arms, aside from infusion reactions which occurred in 70% of patients treated with CBP501. Conclusions While this randomized phase II trial met its primary endpoint of PFS at 4 months, other parameters such as response rate and overall survival suggest that the addition of CBP501 does not improve the efficacy of standard chemotherapy for MPM. [ABSTRACT FROM AUTHOR]

Background: Observational studies suggest that higher levels of 25-hydroxyvitamin D3 (25(OH)D) are associated with a reduced risk of colorectal cancer and improved survival of colorectal cancer patients. However, the influence of vitamin D status on cancer recurrence and survival of patients with stage III colon cancer is unknown. Patients and methods: We prospectively examined the influence of post-diagnosis predicted plasma 25(OH)D on outcome among 1016 patients with stage III colon cancer who were enrolled in a National Cancer Institute-sponsored adjuvant therapy trial (CALGB 89803). Predicted 25(OH)D scores were computed using validated regression models. We examined the influence of predicted 25(OH)D scores on cancer recurrence and mortality (disease-free survival; DFS) using Cox proportional hazards. Results: Patients in the highest quintile of predicted 25(OH)D score had an adjusted hazard ratio (HR) for colon cancer recurrence or mortality (DFS) of 0.62 (95% confidence interval [CI], 0.44-0.86), compared with those in the lowest quintile (Ptrend = 0.005). Higher predicted 25(OH)D score was also associated with a significant improvement in recurrence-free survival and overall survival (Ptrend = 0.01 and 0.0004, respectively). The benefit associated with higher predicted 25(OH)D score appeared consistent across predictors of cancer outcome and strata of molecular tumor characteristics, including microsatellite instability and KRAS, BRAF, PIK3CA, and TP53 mutation status. Conclusion: Higher predicted 25(OH)D levels after a diagnosis of stage III colon cancer may be associated with decreased recurrence and improved survival. Clinical trials assessing the benefit of vitamin D supplementation in the adjuvant setting are warranted. [ABSTRACT FROM AUTHOR]

Background The goal of this study was to create a comprehensive model for malignant pleural mesothelioma patient survival utilizing continuous, time-varying estimates of disease volume from computed tomography (CT) imaging in conjunction with clinical covariates. Patients and methods Serial CT scans were obtained during the course of clinically standard chemotherapy for 81 patients. The pleural disease volume was segmented for each of the 281 CT scans, and relative changes in disease volume from the baseline scan were tracked over the course of serial follow-up imaging. A prognostic model was built using time-varying disease volume measurements in conjunction with clinical covariates. Results Over the course of treatment, disease volume decreased by an average of 19%, and median patient survival was 12.6 months from baseline. In a multivariate survival model, changes in disease volume were significantly associated with patient survival along with disease histology, Eastern Cooperative Oncology Group performance status, and presence of dyspnea. Conclusions Analysis of the trajectories of disease volumes during chemotherapy for patients with mesothelioma indicates that increasing disease volume was significantly and independently associated with poor patient prognosis in both univariate and multivariate survival models. [ABSTRACT FROM PUBLISHER]

Background The unmet need for effective and tolerable mPC treatments is high. PC pts with a germline BRCA1 and/or BRCA2 mutation (gBRCAm) have shown response to the PARP inhibitor olaparib (O; Kaufman 2015). POLO (NCT02184195), the first Phase III trial to evaluate the efficacy of maintenance PARP inhibitor treatment in PC, demonstrated a statistically significant and clinically meaningful improvement in progression-free survival (PFS) from maintenance O vs placebo (P) for pts with a gBRCAm and mPC whose disease had not progressed during PBC (median 7.4 vs 3.8 months; hazard ratio [HR] 0.53; 95% CI 0.35–0.82; P = 0.004). At 2 years, 22.1% of pts on O vs 9.6% of pts on P were progression free. At an interim overall survival analysis (46% maturity), the HR was 0.91 (95% CI 0.56–1.46; P = 0.68). Safety was consistent with the known profile for O (Golan 2019). Methods POLO is a randomized, double-blind, placebo-controlled trial of pts with a gBRCAm and pancreatic adenocarcinoma who had received ≥16 weeks of first-line PBC for mPC without progression. There was no limit to duration of chemotherapy. Pts were randomized 3:2 to maintenance O tablets (300 mg bid) or P. Treatment began 4–8 weeks after the last PBC dose, continuing until investigator-assessed progression or unacceptable toxicity. The primary endpoint, PFS, and objective response were assessed by blinded independent central review (modified RECIST 1.1). Results Objective response rate among pts with measurable disease at baseline was 23.1% (18/78) in the O and 11.5% (6/52) in the P arm (odds ratio 2.30; 95% CI 0.89–6.76; P = 0.103). Table: 126O Best objective response in the full study population   Olaparib (N = 92)  Placebo (N = 62)  Pts who achieved a response, n (%)  18 (19.6)  6 (9.7)  Pts who achieved a complete response, n (%)  2* (2.2)  0  Median duration of response, months  24.9  3.7  Median time to response, months  5.4  3.6  Pts with stable disease for ≥7 weeks, n (%)  45 (48.9)  34 (54.8)  Pts with continued no evidence of disease, n (%)†  5 (5.4)  0  Disease control rate at 16 weeks, %‡  53.3  37.1    Olaparib (N = 92)  Placebo (N = 62)  Pts who achieved a response, n (%)  18 (19.6)  6 (9.7)  Pts who achieved a complete response, n (%)  2* (2.2)  0  Median duration of response, months  24.9  3.7  Median time to response, months  5.4  3.6  Pts with stable disease for ≥7 weeks, n (%)  45 (48.9)  34 (54.8)  Pts with continued no evidence of disease, n (%)†  5 (5.4)  0  Disease control rate at 16 weeks, %‡  53.3  37.1  * One pt had a partial response to first-line chemotherapy, the other had stable disease; †Applicable to pts who entered the study with no evidence of disease; ‡Proportion of pts with a response, or ≥ 15 weeks of stable disease or no evidence of disease. Table: 126O Best objective response in the full study population   Olaparib (N = 92)  Placebo (N = 62)  Pts who achieved a response, n (%)  18 (19.6)  6 (9.7)  Pts who achieved a complete response, n (%)  2* (2.2)  0  Median duration of response, months  24.9  3.7  Median time to response, months  5.4  3.6  Pts with stable disease for ≥7 weeks, n (%)  45 (48.9)  34 (54.8)  Pts with continued no evidence of disease, n (%)†  5 (5.4)  0  Disease control rate at 16 weeks, %‡  53.3  37.1    Olaparib (N = 92)  Placebo (N = 62)  Pts who achieved a response, n (%)  18 (19.6)  6 (9.7)  Pts who achieved a complete response, n (%)  2* (2.2)  0  Median duration of response, months  24.9  3.7  Median time to response, months  5.4  3.6  Pts with stable disease for ≥7 weeks, n (%)  45 (48.9)  34 (54.8)  Pts with continued no evidence of disease, n (%)†  5 (5.4)  0  Disease control rate at 16 weeks, %‡  53.3  37.1  * One pt had a partial response to first-line chemotherapy, the other had stable disease; †Applicable to pts who entered the study with no evidence of disease; ‡Proportion of pts with a response, or ≥ 15 weeks of stable disease or no evidence of disease. Conclusions Pts with a gBRCAm and mPC whose disease had not progressed on PBC derived a statistically significant and clinically meaningful PFS benefit from maintenance O. O-arm pts were more likely to maintain disease control or achieve a response than P-arm pts, and responses were durable, lasting a median of more than 2 years. Clinical trial identification NCT02184195. Editorial acknowledgement Medical writing assistance was provided by Elin Pyke, MChem, from Mudskipper Business Ltd, funded by AstraZeneca and Merck Sharp & Dohme Corp. a subsidiary of Merck & Co. Inc. Kenilworth, NJ, USA (MSD). Legal entity responsible for the study AstraZeneca and Merck Sharp & Dohme Corp. a subsidiary of Merck & Co. Inc. Kenilworth, NJ, USA (MSD). Funding AstraZeneca and Merck Sharp & Dohme Corp, a subsidiary of Merck & Co, Inc, Kenilworth, NJ, USA. Disclosure D-Y. Oh: Research grant / Funding (self): AstraZeneca; Advisory / Consultancy: Novartis; Advisory / Consultancy: Genentech/Roche; Advisory / Consultancy: Merck Serono; Advisory / Consultancy: Bayer; Advisory / Consultancy: Taiho; Advisory / Consultancy: ASLAN; Advisory / Consultancy: Halozyme. T. Golan: Honoraria (self), Research grant / Funding (self), International coordinating investigator service fee: AstraZeneca; Research grant / Funding (self): MSD Merck; Advisory / Consultancy, Speaker Bureau / Expert testimony: AbbVie. P. Hammel: Research grant / Funding (self): Celgene; Research grant / Funding (self): AstraZeneca; Research grant / Funding (self), Non-remunerated activity/ies: Erythec; Research grant / Funding (self): Halozyme. M. Reni: Honoraria (self), Advisory / Consultancy, Research grant / Funding (self), Non-remunerated activity/ies, Steering committee member: Celgene; Advisory / Consultancy: Baxalta; Advisory / Consultancy: Shire; Advisory / Consultancy: Eli-Lilly; Advisory / Consultancy: Pfizer; Advisory / Consultancy: Novocure; Advisory / Consultancy: Novartis; Advisory / Consultancy, Steering Committee member: AstraZeneca; Advisory / Consultancy, Steering Committee member: Boston Pharma. E. Van Cutsem: Advisory / Consultancy: AstraZeneca; Advisory / Consultancy, Research grant / Funding (self): Bayer; Advisory / Consultancy: Bristol-Myers Squibb; Advisory / Consultancy, Research grant / Funding (self): Celgene; Advisory / Consultancy, Research grant / Funding (self): Lilly; Advisory / Consultancy, Research grant / Funding (self): Merck Sharp & Dohme; Advisory / Consultancy, Research grant / Funding (self): Merck KGaA; Advisory / Consultancy, Research grant / Funding (self): Novartis; Advisory / Consultancy, Research grant / Funding (self): Roche; Advisory / Consultancy, Research grant / Funding (self): Servier; Research grant / Funding (self): Amgen; Research grant / Funding (self): Boehringer Ingelheim; Research grant / Funding (self): Ipsen. T. Macarulla: Honoraria (self): Genzyme; Honoraria (self), Research grant / Funding (institution): Roche; Honoraria (self), Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Sanofi/Aventis; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Shire; Honoraria (self): Tesaro; Advisory / Consultancy: Baxalta; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): Celgene; Advisory / Consultancy, Travel / Accommodation / Expenses: H3B; Advisory / Consultancy: QED; Research grant / Funding (institution): Agios; Research grant / Funding (institution): Aslan; Research grant / Funding (institution): AstraZeneca; Travel / Accommodation / Expenses: Bayer, Merck; Research grant / Funding (institution): Genentech; Research grant / Funding (institution): Hallozyme; Research grant / Funding (institution): Immunomedics; Research grant / Funding (institution): Lilly; Research grant / Funding (institution): Merimarack; Research grant / Funding (institution): Millennium; Research grant / Funding (institution): Novartis, Novocure, Pfizer, Pharmaclynics. M.J. Hall: Research grant / Funding (institution), Travel / Accommodation / Expenses, Non-remunerated activity/ies: AstraZeneca; Research grant / Funding (institution): Merck; Travel / Accommodation / Expenses: Caris Lifesciences; Non-remunerated activity/ies: Myriad; Non-remunerated activity/ies: Ambry; Non-remunerated activity/ies: Invitae; Non-remunerated activity/ies: Foundation Medicine; Non-remunerated activity/ies: Caris; Non-remunerated activity/ies: Merck. J. Oh Park: Honoraria (self), Advisory / Consultancy, Research grant / Funding (self): Celgene; Honoraria (self), Advisory / Consultancy: Sanofi; Honoraria (self), Advisory / Consultancy: Shire; Advisory / Consultancy: Merck; Advisory / Consultancy: Sereno. D. Arnold: Honoraria (self): AstraZeneca; Honoraria (self), Non-remunerated activity/ies: Bayer; Honoraria (self), Non-remunerated activity/ies: BMS; Honoraria (self): Biocompatibles; Honoraria (self): Eli Lilly; Honoraria (self), Non-remunerated activity/ies: MSD; Honoraria (self), Non-remunerated activity/ies: Servier; Honoraria (self), Non-remunerated activity/ies: Sanofi; Honoraria (self), Non-remunerated activity/ies: Roche; Honoraria (self): Terumo; Honoraria (self), Non-remunerated activity/ies: Sirtex. A. Reinacher-Schick: Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Amgen; Honoraria (self), Advisory / Consultancy: Baxalta; Honoraria (self), Advisory / Consultancy: BMS; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Celgene; Honoraria (self), Research grant / Funding (institution): Ipsen; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Lilly; Honoraria (self), Advisory / Consultancy: Merck-Serono; Honoraria (self), Advisory / Consultancy: MSD; Honoraria (self), Advisory / Consultancy: Pfizer; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Roche; Honoraria (self), Advisory / Consultancy: Sanofi-Aventis; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Servier; Honoraria (self): Shire; Research grant / Funding (institution): Astra. G. Tortora: Honoraria (self), Advisory / Consultancy: Celgene; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Merck; Honoraria (self), Advisory / Consultancy: Incyte; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Novartis. H. Algül: Honoraria (self): Celgene; Honoraria (self), Travel / Accommodation / Expenses: Servier; Research grant / Funding (institution): Chugai. E.M. O'Reilly: Advisory / Consultancy: 3DMedcare, Agios, Alignmed, Amgen, Antengene, Aptus, Aslan, Astellas, AstraZeneca; Advisory / Consultancy: Bayer, Beigene, Bioline, BMS, Boston Scientific, Bridgebio, ; Advisory / Consultancy: Carsgen, Celgene, Casi, Cipla, CytomX; Advisory / Consultancy: Daiichi, Debio, Delcath; Advisory / Consultancy: Eisai, Exelixis, Genoscience; Advisory / Consultancy: Halozyme, Hengrui; Advisory / Consultancy: Incyte, Inovio, Ipsen; Advisory / Consultancy: Jazz, Janssen; Advisory / Consultancy: Kyowa Kirin; Advisory / Consultancy: LAM, Lilly, Loxo; Advisory / Consultancy: Merck, Mina; Advisory / Consultancy: Novella; Advisory / Consultancy: Onxeo; Advisory / Consultancy: PCI Biotech, Pfizer, Pieris; Advisory / Consultancy: QED, Redhill; Advisory / Consultancy: Sanofi, Servier, Silenseed, Sillajen, Sobi; Advisory / Consultancy: Targovax, Tekmira, Twoxar; Advisory / Consultancy: Vicus, Yakult, Yiviva; Research grant / Funding (institution): ActaBiologica, Agios, Array, AstraZeneca, Bayer, Beigene, BMS, Casai, Celgene, Exelisis, Genentech, Halozyme, Incyte, Lilly, Mabvax, Novartis, OncoQuest, Polaris Puma, QED, Roche. D. McGuinness: Full / Part-time employment: AstraZeneca. K.Y. Cui: Shareholder / Stockholder / Stock options, Full / Part-time employment: AstraZeneca; Research grant / Funding (institution): Merck and Co. Inc. K. Schlienger: Travel / Accommodation / Expenses, Shareholder / Stockholder / Stock options, Full / Part-time employment: Merck & Co. Inc. G.Y. Locker: Shareholder / Stockholder / Stock options, Full / Part-time employment: AstraZeneca. H.L. Kindler: Advisory / Consultancy, Research grant / Funding (institution): AstraZeneca; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Merck; Advisory / Consultancy: Aldeyra Therapeutics; Advisory / Consultancy: Astellas; Advisory / Consultancy, Travel / Accommodation / Expenses: Boehringer Ingelheim; Advisory / Consultancy, Research grant / Funding (institution): BMS; Advisory / Consultancy: Erytech; Advisory / Consultancy: Five Prime Therapeutics; Advisory / Consultancy: Ipsen Pharmaceuticals; Advisory / Consultancy: Kyowa; Advisory / Consultancy, Travel / Accommodation / Expenses: Paredox Therapeutics; Research grant / Funding (institution): Aduro; Research grant / Funding (institution): Bayer; Research grant / Funding (institution): Deciphera; Research grant / Funding (institution): Glaxo Smith Kline; Research grant / Funding (institution): MedImmune; Research grant / Funding (institution): Lilly; Research grant / Funding (institution): Polaris; Research grant / Funding (institution): Verastem. All other authors have declared no conflicts of interest. [ABSTRACT FROM AUTHOR]