Browsing Over 3689 Presentations
The medical oncologist perspective (ID 297)
- Andrea Necchi (Milan, Italy)
380P - Clinico-pathological features and prognosis of patients with pregnancy associated breast cancer: A matched case control study (ID 3705)
- Ruyan Zhang (Beijing, China)
Abstract
Background
The impact of pregnancy on clinico-pathological features and prognosis of breast cancer remains controversial.We aimed to evaluate the impact of the association of pregnancy with breast cancer on tumor feature and prognosis- overall survival (OS) and disease free survival (DFS).
Methods
We defined Pregnancy Associated Breast Cancer (PABC) as breast cancer diagnosed during pregnancy or within a year following delivery. We enrolled PABC patients(pts) treated at our institution between December 2012 and December 2017 , and for each case, one non-PABC control was matched for stage, age, and year of diagnosis. Chis-quare and Fisher’s exact test, the Kaplan-Meier method, and Cox’s regression model were used. Univariate and multivariate analyses were performed to assess the parameters associated with prognosis.
Results
41 women with PABC were identified; 22 pts were diagnosed during pregnancy and 19 were diagnosed within one year of postpartum. There were more PR negative and triple negative tumors in the PABC(56.1% and 24.4%) than in the non-PABC(31.7% and 4.9%) (p = 0.045 and 0.026 respectively). The HER2 positivity was the same in the two group, both 31.7%. Median DFS in PABC pts was 29.0 months (95% CI range 6.5-51.5 months ) compared with 40.9 months (95% CI range 22.8–58.8 months) in the non-PABC pts(p = 0.167). Median OS in two groups were similar and even longer in PABC group, 82.8 months in PABC pts range(95% CI 39.3-126.5months) compared with 80.1 months (95% CI range 56.7-103.6months) in the non-PABC pts( p = 0.131).
Conclusions
The results show histological features were similar in both groups, except that triple-negative tumors were more common in the PABC group. The survival analyses show similar OS for patients diagnosed with PABC compared with non-PABC patients, and DFS tends to be shorter for PABC but no significant difference was observed.
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.
Tumour biology and pathology (ID 6603)
- Thomas Helleday (Stockholm, Sweden)
- Therese Sorlie (Oslo, Norway)
Q&A led by Discussant (ID 6885)
LBA18 - Clinical outcomes by chemotherapy regimen in patients with RS 26-100 in TAILORx (ID 6136)
- Joseph Sparano (Bronx, NY, United States of America)
Abstract
Background
The recurrence score (RS) based on the 21-gene breast cancer assay predicts chemotherapy benefit if it is high and a low risk of recurrence in the absence of chemotherapy if it is low. There is little information from prospective clinical trials, however, regarding outcomes for patients with a high RS treated with chemotherapy regimens including taxanes and/or anthracyclines.
Methods
Women with hormone-receptor-positive, HER2-negative, axillary-node-negative breast cancer and a high RS of 26-100 were assigned to receive endocrine therapy plus a chemotherapy regimen selected by the treating physician.
Results
Among the 9719 eligible women, 1389 (14%) had a RS of 26-100.The most common chemotherapy regimens included docetaxel/cyclophosphamide in 589 (42%), an anthracycline without a taxane in 334 (24%), an anthracycline and taxane in 244 (18%), cyclophosphamide/methotrexate/5-FU in 52 (4%), other regimens in 81 (6%), and no chemotherapy in 89 (6%). The estimated rates of freedom from recurrence of breast cancer at a distant site were 93.0% (standard error [SE]+0.8%) at 5 years and 86.8% (SE + 1.7%) at 9 years. In contrast, the projected rates of freedom from distant recurrence in this population if treated with endocrine therapy alone was estimated to be 78.8% (SE ± 14.0%) at 5 years and 65.4% (SE ± 10.4%) at 9 years when estimating outcomes based on the treatment effect of chemotherapy noted in the HER2-negative cohort of the B20 trial. Five-year rates of freedom from distant recurrence ranged from 92.3% to 95.5% for all chemotherapy regimens with the exception of CMF (88.5%).
Conclusions
The estimated rate of freedom from distant recurrence in women with a RS of 26-100 treated with a variety of adjuvant taxane and/or anthracycline-containing chemotherapy regimens plus endocrine therapy in the prospective TAILORx trial was 93% at 5 years, an outcome better than expected with endocrine therapy alone in this population.
Clinical trial identification
NCT00310180.
Legal entity responsible for the study
ECOG-ACRIN Cancer Research Group.
Funding
USA National Cancer Institute, Genomic Health.
Disclosure
All authors have declared no conflicts of interest.
LBA58 - BAROCCO: A randomized phase II study of weekly paclitaxel vs cediranib-olaparib combination given with continuous or intermittent schedule in patients with recurrent platinum resistant ovarian cancer (PROC) (ID 2560)
- Nicoletta Colombo (Milan, Italy)
Abstract
Background
Hypoxia induced by antiangiogenic agents could cause a functional impairment of homologous recombination, thus sensitizing wild-type (wt) BRCA tumor cells to PARP inhibition. In a phase II study the combination of cediranib-olaparib increased progression free survival (PFS) in women with recurrent platinum sensitive OC with respect to olaparib.
Methods
123 patients were allocated in a 1:1:1 ratio to receive: 80 mg/m2 weekly paclitaxel up to 24 weeks (control), olaparib 600 mg tablet (300 mg twice daily) together with 20 mg cediranib daily (continuous schedule) or 20 mg cediranib given 5 days/week (intermittent schedule) until progression. PFS comparison between experimental schedules and the control arm (alpha one-sided 5%; power 80% to detect a HR of 0.5) was the primary objective.
Results
Median platinum-free interval was 1.8 mos, 59% of patients were pretreated with >3 chemotherapy lines. Median PFS for paclitaxel, the continuous, and the intermittent schedules were 3.1, 5.7, and 3.8 mos. Estimated HR for PFS in continuous arm vs control was 0.76 (90% CI: 0.49-1.17), p = 0.28 by log-rank test. HR for PFS in intermittent arm vs. control was 1.08 (90% CI: 0.71-1.64), p = 0.76 by log-rank test. In the subgroup gBRCA wt (n = 109) the median PFS for paclitaxel, the continuous, and the intermittent schedules were 2.1, 5.8 and 3.8 mos and HR for PFS in continuous arm vs control was 0.63 (95% CI: 0.36 to 1.10; p = 0.10). The toxicity profile of the study arms was as expected and similar between experimental arms. 11%, 18%, and 7% in control, continuous and intermittent arm discontinued treatment for adverse events. Five serious adverse drug reactions occurred and two of these were fatal: one in the control and one in the continuous arm.
Conclusions
The combination of cediranib and olaparib is effective in heavily pretreated PROC patients with the advantage of an oral administration and good tolerability. The continuous schedule of cediranib-olaparib showed a promising trend towards improved PFS in comparison with weekly paclitaxel particularly in the BRCA wt population.
Clinical trial identification
IRFMN-OVA-7289, EudraCT: 2016-003964-38, NCT03314740.
Legal entity responsible for the study
Istituto di Ricerche Farmacologiche Mario Negri IRCCS.
Funding
AstraZeneca.
Disclosure
N. Colombo: Honoraria (self), Advisory / Consultancy: Roche/Genentech; Honoraria (self), Advisory / Consultancy: PharmaMar; Honoraria (self), Advisory / Consultancy: AstraZeneca; Honoraria (self), Advisory / Consultancy: Tesaro; Advisory / Consultancy: Clovis Oncology; Advisory / Consultancy: Pfizer; Advisory / Consultancy: MSD Oncology; Advisory / Consultancy: BioCad; Advisory / Consultancy: Takeda. G. Tognon: Advisory / Consultancy: Amgen; Speaker Bureau / Expert testimony, Research grant / Funding (institution): Roche; Speaker Bureau / Expert testimony, Research grant / Funding (institution): AstraZeneca; Speaker Bureau / Expert testimony: Tesaro. M. Ratti: Travel / Accommodation / Expenses: Tesaro Bio. All other authors have declared no conflicts of interest.
Closing remarks, overview, summary and interactive Q&A (ID 531)
- Rosa Giuliani (Manchester, United Kingdom)
1726P - A peptidase-potentiated alkylating agent melflufen is effective anti-neoplastic agent in osteosarcoma (ID 4214)
- Konstantin Byrgazov (Vienna, Austria)
Abstract
Background
High-grade osteosarcoma (HGOS) is the most common primary malignant bone tumor. In metastatic patients, survival rates are poor and remained virtually unchanged over the past 30 years. Furthermore, recent randomized trials failed to improve the efficacy of current chemotherapy. Here we tested the anti-neoplastic activity of a novel peptide-conjugated alkylator melflufen in preclinical osteosarcoma setting. Due to its high lipophilicity melflufen rapidly enters tumor cells where it is immediately cleaved by peptidases leading to entrapment and enrichment of alkylating payload. Overexpression of peptidases is often seen in tumor cells and can thus lead to increased melfufen sensitivity. In osteosarcoma, over-expression of aminopeptidase N (ANPEP/CD13) has been associated with poor survival and metastasis suggesting that melflufen may represent a valid new therapeutic option.
Methods
Gene expression of ANPEP/CD13 in patient samples from GEO datasets was analyzed using standard tools. Anti-neoplastic activity of melflufen and was evaluated in a panel of 11 osteosarcoma cell lines including early passage patient-derived primary lines. In vitro anti-neoplastic activity was examined using survival and apoptosis assays. In vivo activity of melflufen was tested in a chicken embryo xenograft model.
Results
Melflufen has demonstrated superior anti-neoplastic activity in comparison to other alkylating agents including melphalan, cyclophosphamide, ifosfamide, busulfan, and bendamustine. Melflufen was active in all osteosarcoma cell lines including the cells resistant to methotrexate, etoposide, and talazoparib. Anti-neoplastic activity of melflufen could be hindered by ANPEP inhibitor bestatin. Furthermore, in vivo administration of melflufen reduced tumor growth and metastasis of highly aggressive 143B osteosarcoma cells in a xenograft model.
Conclusions
Melflufen has demonstrated promising results in preclinical osteosarcoma model showing anti-neoplastic activity superior to other alkylating agents and PARP inhibitor talazoparib. Melflufen’s favorable toxicity profile suggests that it might represent a novel valid therapeutic approach for osteosarcoma patients with poor response to chemotherapy and metastasis.
Legal entity responsible for the study
The authors.
Funding
Oncopeptides AB.
Disclosure
A. Slipicevic: Full / Part-time employment: Oncopeptides AB. K. Byrgazov: Research grant / Funding (self): Oncopeptides AB. F. Lehmann: Full / Part-time employment: Oncopeptides AB; Leadership role: EpiEndo Pharmaceuticals. T. Lion: Honoraria (self), Advisory / Consultancy, Research grant / Funding (self): Incyte. All other authors have declared no conflicts of interest.
1458PD - Phase III study comparing second- and third-generation regimens with concurrent thoracic radiotherapy in patients with unresectable stage III non-small cell lung cancer: 10-year follow-up of West Japan thoracic oncology group WJTOG0105 (ID 1634)
- Yoshitaka Zenke (Kashiwa, Chiba, Japan)
Abstract
Background
Third-generation regimens with chemoradiotherapy (CRT) has been established as one of a standard treatment for patients with unresectable stage III non-small cell lung cancer (NSCLC) after first results of the phase III WJTOG0105 trial. However, the long-term survival and cumulative incidences of toxicity associated with CRT remains unclear. We report survival and late toxicities with a follow-up period of 10 years.
Methods
Eligible patients were randomly assigned to A (control), four cycles of mitomycin (8 mg/m2 on day 1)/vindesine (3 mg/m2 on days 1, 8)/cisplatin (80 mg/m2 on day 1) plus thoracic radiotherapy (TRT) 60 Gy; B, weekly irinotecan (20 mg/m2)/carboplatin (area under the plasma concentration-time curve [AUC] 2) for 6 weeks plus TRT 60 Gy, followed by two courses of irinotecan (50 mg/m2 on days1, 8)/carboplatin (AUC 5 on day1); C, weekly paclitaxel (40mg/m2)/carboplatin (AUC 2) for 6 weeks plus TRT 60 Gy, followed by two courses of paclitaxel (200mg/m2 on day1)/carboplatin (AUC 5 on day 1). Kaplan-Meier survival curves and 5- and 10-year survival probabilities were calculated. Late toxicities were defined as occurring later than 90 days after CRT initiation.
Results
From September 2001 to September 2005, 440 patients (arm A, n = 146; arm B arm, n = 147; arm C, n = 147) were enrolled. In the arm A, B and arm C, median overall survival (OS) time was 20.5, 19.8 and 22.0 months, 5-year survival probability was 20.9%, 16.0% and 18.2%, and 10-year survival probability was 13.6%, 7.5% and 15.2%, respectively. There were no significant differences in OS among the treatment arms. The 10-year progression-free survival (PFS) probability was 8.5%, 6.5%, and 11.1% in arm A, B and C. %Grade 3/4 late toxicities were 3.4% (heart 0.7%, lung 2.7%) in arm A and only lung 3.4% in arm B and lung 4.1% in arm C. No additional cases of late toxicity (Grade 3/4) were seen since the initial report.
Conclusions
Arm C shows similar efficacy and toxicity profiles compared with arm A, even 10 years after starting treatment. However, 10-year PFS probability was only 11%, and thus new treatment strategies incorporating immunotherapy are required.
Clinical trial identification
UMIN000030811.
Legal entity responsible for the study
West Japan Oncology Group.
Funding
Has not received any funding.
Disclosure
Y. Zenke: Honoraria (self): Boheniger Ingelheim; Honoraria (self): Chugai Pharma; Honoraria (self): AstraZeneca; Honoraria (self): Lilly; Honoraria (self): Taiho Pharmaceutical; Honoraria (self): MSD Oncology; Research grant / Funding (institution): MSD. M. Tsuboi: Honoraria (self): AstraZeneca; Honoraria (self): Lilly; Honoraria (self): Boehringer Ingelheim; Honoraria (self): Daiichi Sankyo; Honoraria (self): Chugai Pharma; Honoraria (self): Taiho Pharmaceutical; Honoraria (self): Teijin Pharma; Honoraria (self): Johnson and Johnson; Honoraria (self): Coviden; Honoraria (self): Novartis; Honoraria (self): MSD; Honoraria (self): Ono Pharmaceutical; Honoraria (self): Bristol-Myers Squibb; Research grant / Funding (institution): Boehringer Ingelheim. M. Satouchi: Honoraria (self): AstraZeneca; Honoraria (self): MSD; Honoraria (self): Chugai Pharma; Honoraria (self): Taiho Pharmaceutical; Honoraria (self): Pfizer; Honoraria (self): Boheriner Ingelheim; Honoraria (self): Bristol-Myers Squibb; Honoraria (self): Novartis; Honoraria (self): Lilly; Research grant / Funding (institution): Chugai; Research grant / Funding (institution): AstraZeneca; Research grant / Funding (institution): MSD; Research grant / Funding (institution): Pfizer; Research grant / Funding (institution): Boehringer Ingelheim; Research grant / Funding (institution): Bristol-Myers Squibb; Research grant / Funding (institution): Lilly; Research grant / Funding (institution): AbbVie; Research grant / Funding (institution): Ignyta. H. Daga: Honoraria (self): MSD; Honoraria (self): Boehringer Ingelheim; Honoraria (self): Chugai; Research grant / Funding (institution): AstraZeneca; Research grant / Funding (institution): Chugai. D. Fujimoto: Honoraria (self): AstraZeneca; Honoraria (self): Ono Pharmaceutical; Honoraria (self): Bristol-Myers Squibb; Honoraria (self): Taiho Pharmaceutical; Honoraria (self): Chugai Pharama; Honoraria (self): MSD; Honoraria (self): Boehringer Ingelheim; Honoraria (self): Lilly; Research grant / Funding (institution): AstraZeneca. M. Mori: Honoraria (self): AstraZeneca; Honoraria (self): Chugai Pharma; Honoraria (self): MSD; Honoraria (self): Ono Pheramceutical; Honoraria (self): Boehringer Ingelheim; Honoraria (self): Lilly; Research grant / Funding (institution): Chugai Pharma. T. Hirashima: Honoraria (self): Ono pharmaceutical; Honoraria (self): MSD; Honoraria (self): AstraZeneca; Honoraria (self): Lilly; Honoraria (self): Chugai Pharma; Honoraria (self): Brisotol-Myers Squibb; Honoraria (self): Pfizer; Honoraria (self): Kyowa-Hakko-Kirin; Honoraria (self): Boehringer Ingelheim; Research grant / Funding (institution): Ono Pharmaceutical; Research grant / Funding (institution): MSD; Research grant / Funding (institution): AstraZeneca; Research grant / Funding (institution): Lilly; Research grant / Funding (institution): Brisotol-Myers Squibb; Research grant / Funding (institution): Boehringer Ingelheim; Research grant / Funding (institution): Merck Serono; Research grant / Funding (institution): Taiho Pharmaceutical. N. Yamamoto: Honoraria (self): Bristol-Myers Squibb; Research grant / Funding (institution): Bristol-Myers Squibb. K. Nakagawa: Honoraria (self), Research Funding(instistution): Astellas Pharma Inc.; Honoraria (self), Research Funding(instistution): AstraZeneca K.K.; Honoraria (self), Research Funding(instistution): MSD K.K.; Honoraria (self), Research Funding(instistution): Ono Pharmaceutical Co.,Ltd.; Honoraria (self), Research Funding(instistution): Daiichi Sankyo Co., Ltd.; Honoraria (self), Research Funding(instistution): Taiho Pharmaceutical Co.,Ltd.; Honoraria (self), Research Funding(instistution): Bristol-Myers Squibb Company; Honoraria (self): KYORIN Pharmaceutical Co.,Ltd.; Honoraria (self): Nichi-Iko Pharmaceutical Co., Ltd.; Honoraria (self): Hisamitsu Pharmaceutical Co.,Inc.; Honoraria (self), Research Funding(instistution): Takeda Pharmaceutical Co.,Ltd.; Honoraria (self), Research Funding(instistution): Chugai Pharmaceutical Co.,Ltd.; Honoraria (self), Research Funding(instistution): Eli Lilly Japan K.K.; Honoraria (self): Nippon Boehringer Ingelheim Co.,Ltd.; Honoraria (self), Research Funding(instistution): Novartis Pharma K.K.; Honoraria (self), Research Funding(instistution): Pfizer Japan Inc.; Honoraria (self): Thermo Fisher Scientific K.K.; Advisory / Consultancy, Research Funding(instistution): Astellas Pharma Inc.; Advisory / Consultancy: Takeda Pharmaceutical Co.,Ltd.; Research grant / Funding (institution): Merck Serono Co., Ltd. All other authors have declared no conflicts of interest.
Presentation by expert (ID 103)
- Michael Weller (Zurich, Switzerland)
Best Poster Award (ID 7339)
108P - Biological difference of tumour mutational burden (TMB) and microsatellite instability (MSI) status in patients (pts) with somatic vs germline BRCA1/2-mutated advanced gastrointestinal (GI) cancers using cell-free DNA (cfDNA) sequencing analysis in the GOZILA study (ID 3328)
- Yasuyuki Kawamoto (Sapporo, Hokkaido, Japan)
Abstract
Background
A novel approach to differentiate somatic vs. germline BRCA1/2 mutations in cfDNA using a beta binomial model (AACR 2018, abst #4272) may enable identification of pts with advanced GI tumors who are likely to benefit from a PARP inhibitor. The results from the GOZILA study, the Nationwide Cancer Genome Screening Project utilizing Guardant360, are presented here.
Methods
Pts with advanced GI tumors who were appropriate for any systemic therapy and had progressed following at least one prior treatment were eligible. We investigated the prevalence of somatic vs. germline BRCA1/2 mutations and the association between BRCA1/2 mutations, TMB and MSI.
Results
From Jan 2018 to Mar 2019, 850 pts were prospectively enrolled among 26 major cancer centers in Japan. Of 40 (4.7%) actionable BRCA1/2 mutations, 14 were germline: esophagus (squamous cell carcinoma only), 2 pts (N = 62, 3.2%); stomach, 2 pts (N = 131, 1.5%); colorectum, 3 pts (N = 377, 0.8%); pancreas, 3 pts (N = 157, 1.9%); biliary tract, 4 pts (N = 77, 5.2%); and others, none (N = 31, 0%). Notably, the majority of BRCA1/2 mutations (75%) in pts with esophageal, pancreas and biliary tract cancers were germline, while 81% of BRCA1/2 mutations in pts with stomach and colorectal cancers were somatic (p = 0.001). Median TMB of pts with germline BRCA1/2 mutations was significantly lower than those with somatic BRCA1/2 mutations (p = 0.042). In addition, all pts with germline BRCA1/2 mutations were microsatellite stable, while 19% of pts with somatic BRCA1/2 mutations were MSI-high.
Conclusions
Analysis of cfDNA identified a unique subset of pts with germline BRCA1/2 mutations in advanced GI cancers. Given the association of these findings with efficacy of PARP inhibitor and immune-based therapies, these findings suggest that the identification of BRCA1/2 mutations and their germline-somatic origin may have future implications for therapy selection.
Clinical trial identification
UMIN000029315.
Legal entity responsible for the study
SCRUM-Japan GI-SCREEN.
Funding
Guardant Health, Ono Pharmaceutical.
Disclosure
Y. Kawamoto: Honoraria (self): Taiho Pharmaceutical Co., Ltd.; Honoraria (self): Daiichi Sankyo Co., Ltd.; Honoraria (self): Takeda Pharmaceutical Co., Ltd.; Honoraria (self): Chugai Pharmaceutical Co., Ltd.; Honoraria (self): Merck Biopharma Co., Ltd.; Honoraria (self): Eli Lilly Japan K.K.. Y. Nakamura: Research grant / Funding (institution): Ono Pharmaceutical; Research grant / Funding (institution): Taiho Pharmaceutical. M. Ikeda: Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Novartis Pharma; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Bayer Yakuhin; Research grant / Funding (institution): Bristol-Myers Squibb; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Eisai; Honoraria (self): Taiho Pharmaceutical; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Eli Lilly Japan; Research grant / Funding (institution): Yakult; Advisory / Consultancy: Otsuka Pharmaceutical; Advisory / Consultancy: Daiichi-Sankyo; Honoraria (self): Sumitomo Dainippon Pharma; Honoraria (self), Advisory / Consultancy: Teijin Pharma; Honoraria (self): EA Pharma; Honoraria (self): MSD; Advisory / Consultancy, Research grant / Funding (institution): ASLAN Pharmaceuticals; Advisory / Consultancy, Research grant / Funding (institution): Chugai Pharmaceutical; Research grant / Funding (institution): Ono Pharmaceutical; Research grant / Funding (institution): AstraZeneca; Research grant / Funding (institution): Merck Serono; Research grant / Funding (institution): Nano Carrier; Honoraria (self): Gilead. H. Bando: Honoraria (self): Taiho Pharmaceutical company; Honoraria (self): Eli Lilly; Research grant / Funding (self): Sysmex; Research grant / Funding (self): AstraZeneca. T. Esaki: Honoraria (self), Research grant / Funding (institution): Taiho; Honoraria (self): Chugai; Honoraria (self), Research grant / Funding (institution): Ono; Honoraria (self): Takeda; Honoraria (self): Bayer; Honoraria (self): Eli Lilly; Research grant / Funding (institution): Astellas; Research grant / Funding (institution): MSD; Research grant / Funding (institution): Daiichi-Sankyo; Research grant / Funding (institution): Merck Serono; Research grant / Funding (institution): Dainippon Sumitomo; Research grant / Funding (institution): Novartis. M. Ueno: Honoraria (self), Research grant / Funding (institution): Taiho Pharmaceutical; Honoraria (self), Research grant / Funding (institution): Yakult Honsha; Honoraria (self), Research grant / Funding (institution): AstraZeneca; Honoraria (self): Novartis; Honoraria (self): Lilly; Honoraria (self): Teijin Pharma; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Shire; Honoraria (self), Research grant / Funding (institution): Ono Pharmaceutical; Honoraria (self), Research grant / Funding (institution): Merck Serono; Research grant / Funding (institution): Daiichi Sankyo; Research grant / Funding (institution): Eisai; Research grant / Funding (institution): MSD; Research grant / Funding (institution): NanoCarrier; Research grant / Funding (institution): Dainippon Sumitomo Pharma; Research grant / Funding (institution): Incyte; Research grant / Funding (institution): ASLAN Pharmaceuticals. T. Nishina: Honoraria (self), Research grant / Funding (institution): Taiho pharmaceutinal; Honoraria (self), Research grant / Funding (institution): Chugai Pharma; Honoraria (self), Research grant / Funding (self): Merck Serono; Honoraria (self), Research grant / Funding (institution): Bristol-Myers Suibb; Honoraria (self): Nihonkayaku; Honoraria (self), Research grant / Funding (institution): Lilly Japan; Honoraria (self), Research grant / Funding (institution): Ono Pharmaceutical; Research grant / Funding (institution): Dainippon Sumitomo Pharma; Research grant / Funding (institution): MSD; Research grant / Funding (institution): Diichi Sankyo. E. Oki: Speaker Bureau / Expert testimony: Taiho Pham; Speaker Bureau / Expert testimony: Yakult Honsha; Speaker Bureau / Expert testimony: Merck; Speaker Bureau / Expert testimony: Chugai Pham; Speaker Bureau / Expert testimony: Takeda Pharm; Speaker Bureau / Expert testimony: Eli Lilly; Speaker Bureau / Expert testimony: Bayer. T. Denda: Speaker Bureau / Expert testimony: DAIICHI SANKYO COMPANY, LIMITED. T. Mizukami: Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): Eli Lilly Japan; Advisory / Consultancy: Bristol-Myers Squibb Company; Speaker Bureau / Expert testimony: Takeda Pharmaceutical; Research grant / Funding (institution): TAIHO Pharmaceutical. N. Okano: Honoraria (self): Taiho Pharmaceutical; Honoraria (self): Merck Serono; Honoraria (self): Eisai; Honoraria (self): Ono Pharmaceutical; Honoraria (self): Yakult Honsha; Honoraria (self): Takeda; Honoraria (self): J-Pharma; Honoraria (self): Kyowa Hakko Kirin. M.I. Lefterova: Shareholder / Stockholder / Stock options, Full / Part-time employment: Guardant Health. J.I. Odegaard: Shareholder / Stockholder / Stock options, Full / Part-time employment: Guardant Health. H. Taniguchi: Honoraria (self): Chugai; Honoraria (self), Research grant / Funding (self): Takeda; Honoraria (self): Taiho; Honoraria (self): Eli Lilly; Research grant / Funding (self): Daiichi-Sankyo; Research grant / Funding (self): Sysmex. C. Morizane: Honoraria (self), Research grant / Funding (institution): Pfizer; Honoraria (self), Advisory / Consultancy: Novartis; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Yakult Honsha; Honoraria (self): Lilly; Honoraria (self), Research grant / Funding (institution): Nobelpharma; Honoraria (self): Fujifilm; Honoraria (self): Teijin Pharma; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Taiho Pharmaceutical; Honoraria (self), Research grant / Funding (institution): Eisai; Advisory / Consultancy: Abbvie; Research grant / Funding (institution): ONO PHARMACEUTICAL; Research grant / Funding (institution): J-Pharma. T. Yoshino: Research grant / Funding (self): Novartis Pharma K.K.; Research grant / Funding (self): MSD.K.K.; Research grant / Funding (self): Sumitomo Dainippon Pharma Co., Ltd.; Research grant / Funding (self): CHUGAI PHARMACEUTICAL Co., Ltd.; Research grant / Funding (self): Sanofi K.K.; Research grant / Funding (self): DAIICHI SANKYO Co., Ltd.; Research grant / Funding (self): PAREXEL International Inc.; Research grant / Funding (self): ONO PHARMACEUTICAL Co., Ltd. All other authors have declared no conflicts of interest.