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Background:We aimed to determine the role of palliative resection in metastatic colorectal cancer (mCRC) and ascertain which patient populations would benefit most from this treatment.Methods:A total of 1015 patients diagnosed with mCRC at Seoul National University Hospital between 2000 and 2009 were retrospectively studied.Results:Of the 1015 patients, 168 patients with only liver and/or lung metastasis received curative resection. The remaining 847 patients were treated with palliative chemotherapy and/or palliative resection combined with best supportive care. Palliative resection was performed in 527 (62.2%) cases (complete resection with negative margin (R0) in 93, R1/2 in 434). Resected patients had a more prolonged median overall survival (OS) than unresected patients (21.3 vs 14.1 months; P<0.001). In multivariate analysis, R0 resection was found to be associated with a superior OS compared with R1/2 resection (51.3 vs 19.1 months; P<0.001) and no resection (51.3 vs 14.1 months; P<0.001). When we performed propensity score matching, palliative resection was found to be related to prolonged OS (hazard ratio=0.72, 95% confidence interval=0.59-0.89; P=0.003).Conclusion:Palliative resection without residual disease and chemotherapy confers a longer-term survival outcome than palliative chemotherapy alone in mCRC patient subset. [ABSTRACT FROM AUTHOR]

This prospective study was conducted with the Korean Cancer Study Group to evaluate the efficacy and safety of cetuximab combined with modified FOLFOX6 (mFOLFOX6) as first-line treatment in recurrent or metastatic gastric cancer and to identify potential predictive biomarkers. Patients received cetuximab 400 mg m(-2) at week 1 and 250 mg m(-2) weekly thereafter until disease progression. Oxaliplatin (100 mg m(-2)) and leucovorin (100 mg m(-2)) were administered as a 2-h infusion followed by a 46-h continuous infusion of 5-fluorouracil (2400 mg m(-2)) every 2 weeks for a maximum of 12 cycles. Biomarkers potentially associated with efficacy were analysed. Among 38 evaluable patients, confirmed response rate (RR) was 50.0% (95% CI 34.1-65.9). Median time-to-progression (TTP) was 5.5 months (95% CI 4.5-6.5) and overall survival (OS) 9.9 months. Eleven patients having tumour EGFR expression by immunohistochemistry with low serum EGF and TGF-alpha levels showed a 100% RR compared to 37.0% in the remaining 27 patients (P<0.001). Moreover, ligand level increased when disease progressed in seven out of eight patients with EGFR expression and low baseline ligand level. No patient exhibited EGFR amplification or K-ras mutations. Gastric cancer patients with EGFR expression and low ligand levels had better outcomes with cetuximab/mFOLFOX6 treatment. [ABSTRACT FROM AUTHOR]

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]

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]