Background

Entrectinib is a systemic and central nervous system (CNS)-active potent inhibitor of ROS1 and TRKA/B/C. Primary data showed that entrectinib was tolerable and achieved high objective response rates (ORR) in patients (pts) with ROS1-positive (ROS1+), ROS1 inhibitor-naive NSCLC, and in pts with NTRK fusion-positive (NTRK+) NSCLC, including pts with baseline CNS disease. We present data from an additional 5 months of follow-up.

Methods

Pts with locally advanced/metastatic ROS1+ or NTRK+ tumors (with or without baseline CNS disease) confirmed by nucleic acid-based methods, enrolled in global phase 1/2 entrectinib trials (ALKA-372-001 [EudraCT 2012-000148-88], STARTRK-1 [NCT02097810], STARTRK-2 [NCT02568267]) were included. Disease burden was assessed per blinded independent central review (BICR) using RECIST v1.1, after cycle 1 (4 wks) then every 8 wks. Primary endpoints were ORR and duration of response (DOR) by BICR. Secondary endpoints included ORR and DOR in pts with or without baseline CNS disease, and safety. Intracranial (IC) ORR and DOR were evaluated in pts with baseline CNS disease.

Results

There were 53 efficacy-evaluable pts with treatment-naïve, ROS1+ NSCLC and 10 pts with NTRK+ NSCLC. As of 30 Oct 2018 (additional 5 months’ follow-up), BICR ORR: ROS1+ 79.2% (95% CI 65.9–89.2) and NTRK+ 70.0% (95% CI 34.75–93.33) with complete responses in 5 (9.4%) pts and 1 (10.0%) pt, respectively. In ROS1+ NSCLC, median DOR: 24.6 mo (95% CI 12.6–34.8); in pts with and without baseline CNS disease, ORR was 73.9% (95% CI 51.6–89.8) and 83.3% (95% CI 65.3–94.4); IC ORR was 55.0% (95% CI 31.5–76.9); and median IC DOR was 12.9 mo (95% CI 5.6–not estimable). Additional efficacy for NTRK+ NSCLC pts will be presented. Entrectinib was well tolerated with a safety profile consistent with that previously reported; there were no new or unexpected safety findings.

Conclusions

In line with the primary data, in pts with ROS1+ and NTRK+ NSCLC after an additional 5 months of follow-up, entrectinib was well tolerated and showed clinically meaningful, durable systemic and intracranial responses.

Clinical trial identification

ALKA-372-001 [EudraCT 2012-000148-88] STARTRK-1 [NCT02097810] STARTRK-2 [NCT02568267].

Editorial acknowledgement

Medical Writing support was provided by Laura Vergoz and Charlotte Kennerley, PhD of Gardiner-Caldwell Communications and was funded by F. Hoffmann-La Roche.

Legal entity responsible for the study

F. Hoffman-La Roche.

Funding

F. Hoffman-La Roche.

Disclosure

F. de Braud: Advisory / Consultancy, Officer / Board of Directors: TizianaLife Sciences, BMS, Celgene, Novartis, Servier, Pharm Research Associated, Daiichi Sankyo, Ignyta, Amgen, Pfizer, Octimet Oncology, Incyte, Teofarma, Pierre Fabre, Roche, EMD Serono ; Honoraria (self): BMS, Eli Lilly, Roche, Amgen, AstraZeneca, Gentili, Fondazione Menarini, Novartis, MSD, Ignyta, Bayer, Noema S.r.l., ACCMED, Dephaforum S.r.l., Nadirex, Roche, Biotechspert Ltd, PriME Oncology, Pfizer . S. Siena: Advisory / Consultancy: Amgen, Bayer, BMS, CheckmAb, Celgene, Daiichi-Sankyo, Incyte, Merck, Novartis, Roche-Genentech, and Seattle Genetics. F. Barlesi: Research grant / Funding (self), Travel / Accommodation / Expenses: Astra-Zeneca, Bayer, Bristol-Myers Squibb, Boehringer Ingelheim, Eli Lilly Oncology, F. Hoffmann–La Roche Ltd, Novartis, Merck, MSD, Pierre Fabre, Pfizer and Takeda; Research grant / Funding (institution): AbbVie, ACEA, Amgen, Astra-Zeneca, Bayer, Bristol-Myers Squibb, Boehringer Ingelheim, Eisai, Eli Lilly Oncology, F. Hoffmann–La Roche Ltd, Genentech, Ipsen, Ignyta, Innate Pharma, Loxo, Novartis, Medimmune, Merck, MSD, Pierre Fabre, Pfizer, Sanofi-Aventis; Non-remunerated activity/ies: Principal Investigator for Astra-Zeneca, BMS, Merck, Pierre Fabre and Roche sponsored trials (or ISR). A. Drilon: Honoraria (self), Advisory / Consultancy: Ignyta/Genentech/Roche Loxo/Bayer/Lilly Takeda/Ariad/Millenium TP Therapeutics AstraZeneca Pfizer Blueprint Medicines Helsinn Beigene BergenBio Hengrui Therapeutics Exelixis Tyra Biosciences Verastem MORE Health; Research grant / Funding (institution): Pfizer Exelixis GlaxoSmithKlein Teva Taiho PharmaMar; Research grant / Funding (self): Foundation Medicine; Licensing / Royalties: Wolters Kluwer; Travel / Accommodation / Expenses: Merck - Food/Beverage Puma - Food/Beverage; Honoraria (self): Medscape, OncLive, PeerVoice, Physicians Education Resources, Targeted Oncology, Research to Practice. B. Simmons: Full / Part-time employment: Roche (Genentech). X. Huang: Shareholder / Stockholder / Stock options, Full / Part-time employment: Genentech. S. Osborne: Full / Part-time employment: Roche. R.C. Doebele: Shareholder / Stockholder / Stock options: Rain Therapeutics; Advisory / Consultancy: Chair of Scientific Advisory Board for Rain Therapeutics; Honoraria (self): Guardant; Advisory / Consultancy: Pfizer, Trovagene, Ariad, Takeda, AstraZeneca, Genentech/Roche, Ignyta, Loxo, Rain.; Research grant / Funding (self): Ignyta, Loxo, Mirati; Licensing / Royalties: Abbott Molecular, Rain Therapeutics, GVKbio, Chugai, Loxo, Ignyta, Genentech, Ariad, Foundation Medicine, Black Diamond.

Background

In the phase 3 PACIFIC study of patients with unresectable, Stage III NSCLC without progression after chemoradiotherapy (CRT), durvalumab demonstrated significant improvements versus placebo in the primary endpoints of progression-free survival (HR, 0.52; 95% CI, 0.42–0.65; P < 0.0001) and overall survival (OS; HR, 0.68; 95% CI, 0.53–0.87; P = 0.00251). Safety was similar and durvalumab had no detrimental effect on patient-reported outcomes. Here, we report 3-year OS rates for all patients randomized in the PACIFIC study.

Methods

Patients with WHO PS 0/1 (any tumor PD-L1 status) who received ≥2 cycles of platinum-based CRT were randomized (2:1), 1–42 days following CRT, to receive durvalumab 10 mg/kg intravenously every 2 weeks or placebo, up to 12 months, and stratified by age, sex, and smoking history. OS was analyzed using a stratified log-rank test in the ITT population. Medians and OS rates at 12, 24 and 36 months were estimated by Kaplan-Meier method.

Results

In total, 713 patients were randomized of whom 709 received treatment (durvalumab, n = 473; placebo, n = 236). The last patient had completed the protocol-defined 12 months of study treatment in May 2017. As of January 31, 2019 (data cutoff), 48.2% of patients had died (44.1% and 56.5% in the durvalumab and placebo groups, respectively). The median duration of follow-up was 33.3 months (range, 0.2–51.3). Updated OS remained consistent with that previously reported (stratified HR 0.69, 95% CI, 0.55–0.86), with the median not reached (NR; 95% CI, 38.4 months–NR) with durvalumab versus 29.1 months (95% CI, 22.1–35.1) with placebo. The 12-, 24- and 36-month OS rates with durvalumab and placebo were 83.1% versus 74.6%, 66.3% versus 55.3%, and 57.0% versus 43.5%, respectively. After discontinuation, 43.3% and 57.8% in the durvalumab and placebo groups, respectively, received subsequent anticancer therapy (9.7% and 26.6% subsequently received immunotherapy). OS subgroup results will be presented.

Conclusions

Updated OS data from PACIFIC, including 3-year survival rates, underscore the long-term clinical benefit with durvalumab following CRT and further establish the PACIFIC regimen as the standard of care in this population.

Clinical trial identification

NCT02125461.

Editorial acknowledgement

Medical writing support during the preparation of this abstract, which was in accordance with Good Publication Practice (GPP3) guidelines, was provided by Hashem Dbouk, of Cirrus Communications (Macclesfield, UK), an Ashfield company, and was funded by AstraZeneca.

Legal entity responsible for the study

AstraZeneca.

Funding

AstraZeneca.

Disclosure

Y-L. Wu: Honoraria (self), Advisory / Consultancy: AstraZeneca; Honoraria (self): Eli Lilly; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Roche; Honoraria (self): Pierre Fabre; Honoraria (self): Pfizer; Honoraria (self): Sanofi; Advisory / Consultancy: Merck; Advisory / Consultancy, Research grant / Funding (institution): Boehringer Ingelheim. J.E. Gray: Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): AstraZeneca; Honoraria (self), Advisory / Consultancy: Janssen; Honoraria (self), Advisory / Consultancy: Celgene; Honoraria (self), Advisory / Consultancy: Takeda; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Genentech; Honoraria (self), Advisory / Consultancy: Eli Lilly; Honoraria (self), Advisory / Consultancy: Triptych Health Partners; Research grant / Funding (institution): Array; Research grant / Funding (institution): Merck; Research grant / Funding (institution): Epic Sciences; Research grant / Funding (institution): BMS; Research grant / Funding (institution): Boehringer Ingelheim; Research grant / Funding (institution): Trovagene; Research grant / Funding (institution): Loxo; Research grant / Funding (institution): Blueprint; Research grant / Funding (institution): Novartis. A. Villegas: Honoraria (self): AstraZeneca; Honoraria (self): Seattle Genetics. D.B. Daniel: Research grant / Funding (institution): AstraZeneca; Research grant / Funding (institution): E R Squibb & Sons; Research grant / Funding (institution): Boehringer Ingelheim; Research grant / Funding (institution): Genentech; Research grant / Funding (institution): Eli Lilly; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): Pfizer; Research grant / Funding (institution): Celgene; Research grant / Funding (institution): Roche; Research grant / Funding (institution): E1 Therapeutics. D. Vicente: Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: BMS; Advisory / Consultancy: Merck; Advisory / Consultancy: Boehringer Ingelheim; Advisory / Consultancy: Roche. S. Murakami: Research grant / Funding (institution): Takeda; Honoraria (self): AstraZeneca; Honoraria (self): Chugai; Honoraria (self): Ono; Honoraria (self): Merck Sharp and Dohme. R. Hui: Honoraria (self), Advisory / Consultancy: AstraZeneca; Honoraria (self), Advisory / Consultancy: Merck Sharp and Dohme; Honoraria (self), Advisory / Consultancy: Novartis; Advisory / Consultancy: Roche; Honoraria (self), Advisory / Consultancy: Bristol-Myers Squibb. T. Kurata: Honoraria (self), Research grant / Funding (institution): AstraZeneca; Honoraria (self): Ono; Honoraria (self), Research grant / Funding (institution): Bristol Myers Squibb; Honoraria (self), Research grant / Funding (institution): Chugai; Honoraria (self): Lilly; Honoraria (self): Boehringer Ingelheim; Honoraria (self), Research grant / Funding (institution): MSD. A. Chiappori: Speaker Bureau / Expert testimony: Genentech; Speaker Bureau / Expert testimony: Merck; Speaker Bureau / Expert testimony: Takeda; Speaker Bureau / Expert testimony, Research grant / Funding (institution): Novartis; Speaker Bureau / Expert testimony: Boehringer Ingelheim; Speaker Bureau / Expert testimony: Celgene; Research grant / Funding (institution): Bristol Myers Squibb. B.C. Cho: Advisory / Consultancy, Research grant / Funding (institution): AstraZeneca; Advisory / Consultancy, Research grant / Funding (institution): Novartis; Research grant / Funding (institution): Bayer; Research grant / Funding (institution): MOGAM Institute; Research grant / Funding (institution): Dong-A ST; Research grant / Funding (institution): Champions Oncology; Advisory / Consultancy, Research grant / Funding (institution): Janssen; Advisory / Consultancy, Research grant / Funding (institution): Yuhan; Advisory / Consultancy, Research grant / Funding (institution): Ono; Research grant / Funding (institution): Dizal Pharma; Advisory / Consultancy, Research grant / Funding (institution): MSD; Advisory / Consultancy: Boehringer Ingelheim; Advisory / Consultancy: Roche; Advisory / Consultancy: BMS; Advisory / Consultancy: Pfizer; Advisory / Consultancy: Eli Lilly; Advisory / Consultancy: Takeda; Shareholder / Stockholder / Stock options: TheraCanVac Inc. D. Planchard: Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Boehringer Ingelheim; Advisory / Consultancy: BMS; Advisory / Consultancy: Celgene; Advisory / Consultancy: Novartis; Advisory / Consultancy: Pfizer; Advisory / Consultancy: MSD; Advisory / Consultancy: Roche; Advisory / Consultancy: prIME Oncology; Advisory / Consultancy: PeerCME. L. Paz-Ares: Leadership role: Genomica; Honoraria (self), Travel / Accommodation / Expenses, Spouse / Financial dependant: Roche; Honoraria (self), Travel / Accommodation / Expenses: AstraZeneca; Honoraria (self), Travel / Accommodation / Expenses: MSD; Honoraria (self), Travel / Accommodation / Expenses: BMS; Honoraria (self), Travel / Accommodation / Expenses: Lilly; Honoraria (self), Travel / Accommodation / Expenses, Spouse / Financial dependant: Pfizer; Honoraria (self): Merck Serono; Honoraria (self): Pharma Mar; Honoraria (self), Spouse / Financial dependant: Novartis; Honoraria (self): Celgene; Honoraria (self): Sysmex; Honoraria (self), Spouse / Financial dependant: Amgen; Honoraria (self): Incyte; Spouse / Financial dependant: Ipsen; Spouse / Financial dependant, Leadership Role: European Medicines Agency; Spouse / Financial dependant: SERVIER; Spouse / Financial dependant: Sanofi; Spouse / Financial dependant: Merck. C. Faivre-Finn: Advisory / Consultancy, Speaker Bureau / Expert testimony, To institution: AstraZeneca. J.F. Vansteenkiste: Honoraria (self), Research grant / Funding (institution): MSD; Honoraria (self): AstraZeneca; Honoraria (self): Boehringer Ingelheim; Honoraria (self): Eli-Lilly; Honoraria (self): Apotex; Honoraria (self): Roche. M. Taboada: Shareholder / Stockholder / Stock options, Full / Part-time employment: AstraZeneca. P.A. Dennis: Shareholder / Stockholder / Stock options, Full / Part-time employment: AstraZeneca. M. Özgüroğlu: Advisory / Consultancy: Janssen. S.J. Antonia: Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: AstraZeneca; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: BMS; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Merck; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Boehringer Ingelheim; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Novartis; Honoraria (self), Advisory / Consultancy: Memgen; Advisory / Consultancy, Travel / Accommodation / Expenses: FLX Bio; Honoraria (self), Shareholder / Stockholder / Stock options: CBMG. All other authors have declared no conflicts of interest.

Background

Adjuvant chemotherapy has been recommended for patients who have locally advanced rectal cancer. However, the role of adjuvant chemotherapy in patients with positive surgical margin has not been clarified. We investigated the benefit of adjuvant chemotherapy according to the surgical margin in locally advanced rectal cancer.

Methods

A total of 1801 rectal cancer patients staging cT3-4N0-2M0 were included. The patients were eligible when tumors were pathologically confirmed adenocarcinoma, located within 10cm from anal verge, and staged cT3-4N0-2M0. Before surgery, all patients received radiation therapy at a dose of 50.4 Gy in 28 fractions with concurrent 5-fluorouracil or capecitabine. Curative surgery including TME was performed 4 to 8 weeks after radiotherapy. Adjuvant chemotherapy was performed after 4-6 weeks after surgery.

Results

Adjuvant chemotherapy was given to 1531 patients (85.0%). Patients with positive circumferential resection margin or distal resection margin were 205 (11.4%). With patients with positive surgical margin (n = 205), the 5-year recurrence-free survival (RFS) showed a significant difference between adjuvant chemotherapy group and no adjuvant chemotherapy group (50.3% vs. 30.9%, p = 0.01). The 5-year overall survival rate was 72.6% in adjuvant chemotherapy group and 57.2% in no adjuvant chemotherapy group (p = 0.09). With patients with the negative margin (n = 1596), the 5-year RFS rate did not show any difference between two groups (75.6% vs. 76.8%, p = 0.94). On multivariate analysis, adjuvant chemotherapy was significantly associated with RFS in patients who had the positive surgical margin (Hazard ratio (HR): 0.48, 95% confidence interval (CI): 0.25-0.94, p = 0.032). In contrast, there was no significant association between adjuvant chemotherapy and RFS in those with negative surgical margin (HR: 0.99, 95% CI: 0.72-1.35, p = 0.94).

Conclusions

Patients who received adjuvant chemotherapy showed a significantly improved 5-year RFS rate compared with those who did not receive adjuvant chemotherapy if the patients had positive surgical margin. The benefit of adjuvant chemotherapy was more remarkable in patients with positive surgical margin compared to those with negative surgical margin.

Legal entity responsible for the study

The author.

Funding

Has not received any funding.

Disclosure

The author has declared no conflicts of interest.

Background

Three-dimensional (3D) vision technology has recently been validated for the improvement of surgical skills in a simulated setting. This study to assess the current evidence regarding the efficiency and potential advantages of 3D compared with two-dimensional (2D) laparoscopic rectal surgery for rectal cancer.

Methods

We comprehensively searched PubMed, Embase, Cochrane Library, and performed a systematic review and cumulative meta-analysis of all randomized controlled trials (RCTs) and no randomized controlled trials assessing the two approaches.

Results

Four trials including a total of 331 cases were identified. The positive circumferential resection margins (CRM) is significantly lower for 3D (P = 0.02). The operative time was significantly shorter in the 3D group than in the 2D group (P < 0.00001). There were less estimated blood loss (EBL) in the 3D group than in the 2D group (P = 0.02). Perioperative complication rates, conversion rate, harvested lymph nodes, first flatus, and length of stay did not differ significantly between two approaches (P > 0.05).

Conclusions

3D laparoscopic rectal surgery appear to have advantages over the 2D laparoscopic rectal surgery in terms of operation time and positive CRM, however, it is not better than 2D laparoscopic rectal surgery in terms of EBL and postoperative complications.

Legal entity responsible for the study

Laiyuan Li.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

Background

Searching for specific targets in cancer diagnosis and treatment is one of the most important problems in clinical oncology. We put forward a new concept of the emergence of tumor-specific epitopes of integral membrane proteins by changing their topology under mutations, glycosylation and tumor conditions including low pH and hypoxia on the model of Na-dependent phosphate-cotransporter NaPi2b. NaPi2b (SLC34A2, NaPi-IIb, NPT2b) belongs to the SLC34A2 transporters family and is involved in maintaining phosphate homeostasis in the human body. NaPi2b express in a number of normal and malignant tissues, including ovarian, breast and triple-negative breast cancer. It is an integral membrane protein with a large extramembrane domain 4 (EMD4, 234-362 aa), 8 transmembrane domains, N - and C - ends located in the cytoplasm.

Methods

We have cloned the epitope for antibodies MX35 and L2 (20/3) within 311-340 aa region of NaPi2b, which recognition depends on disulfide bonds, glycosylation and is canceled by the mutation at the T330V position. Topology of the protein undergoing significant changes in hypoxia and low pH conditions.

Results

N-terminal domain of NaPi2b can be localized outside the cells during hypoxia and low pH and return to its primary topology at the inner leaflet membrane in normoxia conditions. This reorientation makes it as a potential tumor-specific domain.

Conclusions

The obtained data are of both fundamental and applied importance in the development of new targeted antitumor drugs of high specificity.

Legal entity responsible for the study

Kazan Federal University.

Funding

Russian Government Program of Competitive Growth of KFU.

Disclosure

All authors have declared no conflicts of interest.

Background

KEYNOTE-062 (NCT02494583) was a randomized, active-controlled study of first-line (1L) pembrolizumab (pembro) or pembro+chemotherapy vs chemotherapy (chemo) in patients (pts) with PD-L1 combined positive score ≥1 (CPS ≥1), HER2^–, advanced GC.

Methods

Eligible pts were randomly assigned 1:1:1 to pembro 200 mg Q3W, pembro+chemo (cisplatin 80 mg/m² + 5-FU 800 mg/m²/d on d1-5 Q3W [or capecitabine 1000 mg/m² BID on d1-14 Q3W per local guidelines]) or placebo+chemo Q3W for up to 2 y. Randomization was stratified by region, disease status, and fluoropyrimidine treatment. Primary end points were OS in CPS ≥1 and CPS ≥10 for pembro+chemo vs chemo and pembro vs chemo, and PFS (RECIST v1.1; central review) in CPS ≥1 for pembro+chemo vs chemo. Secondary end point was ORR (RECIST v1.1; central review) in CPS ≥1 for pembro+chemo vs chemo. Final analysis cutoff date was March 26, 2019.

Results

763 pts (281 with CPS ≥10 tumors) were randomly assigned to pembro+chemo (n = 257), pembro (n = 256), or chemo (n = 250). Median follow-up was 11.3 mo. Pembro was noninferior to chemo for OS in CPS ≥1 per prespecified margins. Pembro prolonged OS vs chemo in CPS ≥10 (median 17.4 vs 10.8 mo; HR 0.69; 95% CI 0.49-0.97) but was not tested per analysis plan. Pembro+chemo was not superior to chemo for OS in CPS ≥1 or CPS ≥10; the trend for pembro+chemo was favorable. Pembro+chemo did not significantly prolong PFS in CPS ≥1. ORR was higher with pembro+chemo than with chemo. In pts with microsatellite instability–high tumors, median OS was not reached (pembro) vs 8.5 mo (chemo) (HR 0.29; 95% CI 0.11-0.81) and not reached (pembro+chemo) vs 8.5 mo (chemo) (HR 0.37; 95% CI 0.14-0.97). Grade 3-5 drug-related AE rates were 17% (pembro), 73% (pembro+chemo), and 69% (chemo).

Conclusions

As 1L therapy for advanced GC, pembro was noninferior to chemo for OS in CPS ≥1; improvement in OS was clinically meaningful in CPS ≥10. Pembro+chemo was not superior for OS and PFS in CPS ≥1 or OS in CPS ≥10. The safety profile was more favorable for pembro than for chemo.Table:

125O

Clinical trial identification

NCT02494583.

Editorial acknowledgement

Medical writing and/or editorial assistance was provided by Traci Stuve, MA, of the ApotheCom pembrolizumab team (Yardley, PA, USA). This assistance was funded by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.

Legal entity responsible for the study

Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.

Funding

Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.

Disclosure

H.C. Chung: Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Merck-Serono; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Lilly; Honoraria (self): Foundation Medicine; Advisory / Consultancy, Research grant / Funding (institution): Taiho; Advisory / Consultancy: Celltrion; Advisory / Consultancy: Quintiles; Advisory / Consultancy: BMS; Research grant / Funding (institution): GSK; Research grant / Funding (institution): MSD; Research grant / Funding (institution): BMS-ONO. Y-J. Bang: Advisory / Consultancy, Research grant / Funding (institution): AstraZeneca; Advisory / Consultancy, Research grant / Funding (institution): Novartis; Advisory / Consultancy, Research grant / Funding (institution): Genentech/Roche; Advisory / Consultancy, Research grant / Funding (institution): MSD; Advisory / Consultancy, Research grant / Funding (institution): Merck Serono; Advisory / Consultancy, Research grant / Funding (institution): Bayer; Advisory / Consultancy, Research grant / Funding (institution): BMS; Advisory / Consultancy, Research grant / Funding (institution): Eli Lilly; Advisory / Consultancy, Research grant / Funding (institution): Taiho; Advisory / Consultancy, Research grant / Funding (institution): Daiichi-Sankyo; Advisory / Consultancy, Research grant / Funding (institution): Astellas; Advisory / Consultancy, Research grant / Funding (institution): BeiGene; Advisory / Consultancy, Research grant / Funding (institution): GreenCross; Advisory / Consultancy: Samyang Biopharm; Advisory / Consultancy: Hanmi; Advisory / Consultancy: Genexine; Research grant / Funding (institution): GSK; Research grant / Funding (institution): Pfizer; Research grant / Funding (institution): Boehringer Ingelheim; Research grant / Funding (institution): MacroGenics, Boston Biomedical, FivePrime, Curis, Taiho, Takeda, Ono, CKD Pharma. J. Tabernero: Advisory / Consultancy, Scientific consultancy role: Array Biopharma, AstraZeneca, Bayer, BeiGene, Boehringer Ingelheim, Chugai, Genentech, Inc., Genmab A/S, Halozyme, Imugene Limited, Inflection Biosciences Limited, Ipsen, Kura Oncology, Lilly, MSD, Menarini, Merck Serono, Merrimack, Merus, Molecular Partn. E. Van Cutsem: Advisory / Consultancy: Astellas; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy, Research grant / Funding (institution): Bayer; Advisory / Consultancy, Research grant / Funding (institution): Bristol-Myers Squibb; Advisory / Consultancy, Research grant / Funding (institution): Celgene; Advisory / Consultancy: Incyte; Advisory / Consultancy, Research grant / Funding (institution): Lilly; Advisory / Consultancy, Research grant / Funding (institution): Merck Sharp & Dohme; Advisory / Consultancy, Research grant / Funding (institution): Merck KGaA; Advisory / Consultancy, Research grant / Funding (institution): Novartis; Advisory / Consultancy, Research grant / Funding (institution): Roche; Advisory / Consultancy, Research grant / Funding (institution): Servier; Research grant / Funding (institution): Amgen; Research grant / Funding (institution): Boehringer Ingelheim. C.S. Fuchs: Advisory / Consultancy: Agios; Advisory / Consultancy: Bain Capital; Advisory / Consultancy: Bayer; Advisory / Consultancy: Celgene; Advisory / Consultancy, Shareholder / Stockholder / Stock options, Officer / Board of Directors, unexercised stock options: CytomX; Advisory / Consultancy: Dicerna; Advisory / Consultancy: Eli Lilly; Advisory / Consultancy, Shareholder / Stockholder / Stock options, unexercised stock options: Entrinsic Health; Advisory / Consultancy: Five Prime Therapeutics; Advisory / Consultancy: Genentech; Advisory / Consultancy: Gilead Sciences; Advisory / Consultancy: KEW; Advisory / Consultancy: Merck; Advisory / Consultancy: Merrimack; Advisory / Consultancy: Pfizer; Advisory / Consultancy: Roche; Advisory / Consultancy: Sanofi; Advisory / Consultancy: Taiho; Advisory / Consultancy: Unum. L. Wyrwicz: Research grant / Funding (institution): MSD; Research grant / Funding (institution): Eisai; Research grant / Funding (institution): BMS; Non-remunerated activity/ies, Patent, royalties, other intellectual property: Cervico; Honoraria (self), Travel / Accommodation / Expenses: Amgen; Honoraria (self), Travel / Accommodation / Expenses: Roche; Advisory / Consultancy: Halozyme; Travel / Accommodation / Expenses: Sanofi; Travel / Accommodation / Expenses: Servier. K-W. Lee: Research grant / Funding (institution): Macrogenics; Research grant / Funding (institution): MSD; Research grant / Funding (institution): Ono Pharmaceutical; Research grant / Funding (institution): Green Cross Corp.; Research grant / Funding (institution): ASLAN Pharmaceuticals; Research grant / Funding (institution): AstraZeneca/MedImmune; Research grant / Funding (institution): Five Prime Therapeutics; Research grant / Funding (institution): LSK BioPharma; Research grant / Funding (institution): Merck KGaA; Research grant / Funding (institution): Array BioPharma; Research grant / Funding (institution): Pharmacyclics; Research grant / Funding (institution): Pfizer. M. Garrido: Research grant / Funding (institution): Novartis. W. Mansoor: Honoraria (self), Speaker Bureau / Expert testimony, Speaker\'s Bureau - ESMO 2018: Lilly. M.I. Braghiroli: Honoraria (self), Research grant / Funding (institution): Roche; Honoraria (self), Research grant / Funding (institution): MSD; Research grant / Funding (institution): AstraZeneca; Advisory / Consultancy: Merck. E. Goekkurt: Advisory / Consultancy: MSD; Advisory / Consultancy: BMS; Advisory / Consultancy: Roche; Advisory / Consultancy: Sanofi; Advisory / Consultancy: Merck; Travel / Accommodation / Expenses: Servier. J. Chao: Advisory / Consultancy, Research grant / Funding (institution): Merck; Research grant / Funding (institution): Novonco Therapeutics; Advisory / Consultancy: Lilly; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Boston Biomedical; Advisory / Consultancy: FivePrime Therapeutics. Z.A. Wainberg: Advisory / Consultancy: Sirtex Medical; Advisory / Consultancy: Array BioPharma; Advisory / Consultancy, Research grant / Funding (institution): Five Prime Therapeutics; Advisory / Consultancy: Novartis; Advisory / Consultancy: Lilly; Advisory / Consultancy, Research grant / Funding (institution): Merck; Advisory / Consultancy: Merck KGaA; Advisory / Consultancy: Bristol-Myers Squibb; Advisory / Consultancy: Aduro Biotech; Advisory / Consultancy, Travel / Accommodation / Expenses: Genentech; Research grant / Funding (institution): Plexxikon; Research grant / Funding (institution): Pfizer. U. Kher: Shareholder / Stockholder / Stock options, Full / Part-time employment: Merck & Co., Inc. . S. Shah: Shareholder / Stockholder / Stock options, Full / Part-time employment: Merck & Co., Inc. K. Shitara: Honoraria (self): Novartis; Honoraria (self): AbbVie; Honoraria (self): Yakult; Advisory / Consultancy, Research grant / Funding (institution): Astellas Pharma; Advisory / Consultancy, Research grant / Funding (institution): Lilly; Advisory / Consultancy: Bristol-Myers Squibb; Advisory / Consultancy: Takeda; Advisory / Consultancy: Pfizer; Advisory / Consultancy, Research grant / Funding (institution): Ono Pharmaceutical; Advisory / Consultancy: MSD; Research grant / Funding (institution): Dainippon Sumitomo Pharma; Research grant / Funding (institution): Daiichi Sankyo; Research grant / Funding (institution): Taiho Pharmaceutical; Research grant / Funding (institution): Chugai Pharma; Research grant / Funding (institution): MSD; Research grant / Funding (institution): MediScience. All other authors have declared no conflicts of interest.