- Li-Tzong Chen (Tainan City, Taiwan)
115MO - Long-term efficacy, tolerability and overall survival in patients (pts) with unresectable or metastatic (U/M) PDGFRA D842V-mutant gastrointestinal stromal tumour (GIST) treated with avapritinib: NAVIGATOR phase I trial update (ID 718)
- Yoon-Koo Kang (Seoul, Songpa-gu, Korea, Republic of)
Abstract
Background
PDGFRA D842V-mutant GIST is highly resistant to all kinase inhibitors approved in the European Union for U/M GIST. Avapritinib, a novel KIT/PDGFRA kinase inhibitor, potently inhibits PDGFRA D842V mutants.
Methods
In the NAVIGATOR study (NCT02508532), adult pts with U/M PDGFRA D842V-mutant GIST (regardless of prior therapy) received oral, once-daily avapritinib (dose escalation, 30–600 mg; dose expansion, 300 [recommended phase II dose, RP2D]/400 mg [maximum tolerated dose]). Long-term efficacy and safety in pts with PDGFRA D842V-mutant GIST treated at 300/400 mg from both phases are reported.
Results
As of March 9, 2020 data cut-off (median follow-up, 26 months [mo]), 38 pts with PDGFRA D842V-mutant GIST treated at 300/400 mg achieved an overall response rate (ORR, modified Response Evaluation Criteria in Solid Tumors version 1.1) of 95%, with 5 (13%) complete responses (CR), and 31 (82%) partial responses (PR); of the 5 TKI-naïve pts, 2 had a CR and 3 a PR. Median duration of response was 22 mo (95% confidence interval [CI] 14–not reached [NR]). Median progression-free survival (PFS) was 24 mo (95% CI 18–NR), and median overall survival (OS) was NR; PFS and OS rates at 36 mo were 34% and 71%, respectively. In pts with PDGFRA D842V-mutant GIST who received less than the 300 mg RP2D (n=17), an ORR of 82% was achieved, with 2 (12%) CR and 12 (71%) PR. The most common adverse events (AEs, any grade) in ≥10% of pts with PDGFRA D842V-mutant GIST treated at 300/400 mg were nausea (74%), anemia (68%), diarrhea (66%), fatigue (58%), memory impairment (47%), periorbital edema (45%), decreased appetite (39%), increased lacrimation (34%), and vomiting, abdominal pain, hypokalemia, increased blood bilirubin and peripheral edema (all 32%). A total of 21% of pts discontinued treatment due to drug-related AEs. There were no treatment-related deaths.
Conclusions
In pts with U/M PDGFRA D842V-mutant GIST, avapritinib has clinical activity with durable responses and a tolerable safety profile, with no additional safety signals to those found in the NAVIGATOR study overall GIST population.
Clinical trial identification
NCT02508532.
Editorial acknowledgement
Medical writing support was provided by Cristina Tomas, PhD, and editorial support by Sinead Stewart, both of Paragon, Knutsford, UK, supported by Blueprint Medicines Corporation.
Legal entity responsible for the study
Blueprint Medicines Corporation.
Funding
Blueprint Medicines Corporation.
Disclosure
Y-K. Kang: Honoraria (self): ALX Oncology; Zymeworks; Amgen; Novartis; Macrogenics; Daehwa; Surface Oncology; BMS. R.L. Jones: Research grant/Funding (self): MSD; Honoraria (self): Adaptimmune; Athenex; Blueprint Medicines Corporation; Clinigen; Clinigen, Eisai; Epizyme; Daichii; Deciphera; Helsinn; Immunedesign; Lilly; Merck; PharmaMar; Tracon; UptoDate. M. von Mehren: Non-remunerated activity/ies: Blueprint Medicines Corporation; Non-remunerated activity/ies: Arog Pharmaceuticals; Non-remunerated activity/ies: Deciphera Pharmaceuticals. C. Serrano: Advisory/Consultancy, Research grant/Funding (self): Deciphera Pharmaceuticals; Honoraria (self), Research grant/Funding (self), Travel/Accommodation/Expenses: Bayer AG; Research grant/Funding (self), Travel/Accommodation/Expenses: Pfizer, Inc; Honoraria (self), Advisory/Consultancy: Blueprint Medicines Corporation; Travel/Accommodation/Expenses: PharmaMar; Travel/Accommodation/Expenses: Novartis; Travel/Accommodation/Expenses: Lilly. S. George: Advisory/Consultancy, Research grant/Funding (self): Blueprint Medicines Corporation; Research grant/Funding (self): Deciphera Pharmaceuticals; Research grant/Funding (self): Pfizer; Research grant/Funding (self): Bayer; Research grant/Funding (self): Ariad; Research grant/Funding (self): Novartis. M.C. Heinrich: Research grant/Funding (self): Blueprint Medicines Corporation; Honoraria (self): MolecularMD; Honoraria (self): Novartis; Honoraria (self): Deciphera Pharmaceuticals. P. Schöffski: Honoraria (self): Deciphera Pharmaceuticals; Non-remunerated activity/ies: Exelixis; Non-remunerated activity/ies: Plexxikon; Non-remunerated activity/ies: Eisai; Non-remunerated activity/ies: Loxo; Non-remunerated activity/ies: Lilly; Non-remunerated activity/ies: Blueprint Medicines Corporation; Non-remunerated activity/ies: Ellipses Pharma; Non-remunerated activity/ies: Merck; Non-remunerated activity/ies: Servier; Non-remunerated activity/ies: Genmab; Non-remunerated activity/ies: Adaptimmune; Non-remunerated activity/ies: Intellisphere; Non-remunerated activity/ies: Transgene; Research grant/Funding (self): MSD; Research grant/Funding (self): Ipsen. O. Mir: Advisory/Consultancy: Eli Lilly; Advisory/Consultancy: Janssen; Advisory/Consultancy: Lundbeck; Advisory/Consultancy: Pfizer; Advisory/Consultancy: Roche; Advisory/Consultancy: Servier; Advisory/Consultancy: Vifor Pharma; Shareholder/Stockholder/Stock options: Amplitude Surgical; Shareholder/Stockholder/Stock options: Transgene; Shareholder/Stockholder/Stock options: Ipsen. P.A. Cassier: Honoraria (self): Blueprint Medicines Corporation; Non-remunerated activity/ies: AbbVie; Non-remunerated activity/ies: Bayer; Non-remunerated activity/ies: BMS; Non-remunerated activity/ies: Merck; Non-remunerated activity/ies: Serono; Non-remunerated activity/ies: MSD; Non-remunerated activity/ies: Novartis; Non-remunerated activity/ies: Roche/Genentech; Non-remunerated activity/ies: GSK; Non-remunerated activity/ies: Janssen; Non-remunerated activity/ies: Lilly. P. Rutkowski: Honoraria (self): Blueprint Medicines Corporation; Honoraria (self): Novartis; Honoraria (self): BMS; Honoraria (self): MSD; Honoraria (self): Roche; Honoraria (self): Pierre Fabre; Honoraria (self): Pfizer. W.D. Tap: Honoraria (self): Blueprint Medicines Corporation; Honoraria (self): Eli Lilly; Honoraria (self): EMD Serono; Honoraria (self): Eisai; Honoraria (self): Janssen; Honoraria (self): Immune Design; Honoraria (self): Daiichi Sankyo; Honoraria (self): Loxo; Honoraria (self): GSK; Honoraria (self): Agios Pharmaceuticals; Honoraria (self): NanoCarrier; Honoraria (self): Deciphera Pharmaceuticals. S.P. Chawla: Research grant/Funding (self): Amgen; Research grant/Funding (self): Roche; Research grant/Funding (self): Threshold Pharmaceuticals; Research grant/Funding (self): GSK; Research grant/Funding (self): CytRx Corporation; Research grant/Funding (self): Ignyta; Research grant/Funding (self): Immune Design; Research grant/Funding (self): Tracon Pharma; Research grant/Funding (self): SARC; Research grant/Funding (self): Karyopharm Therapeutics; Research grant/Funding (self): Janssen. H. Shi: Full/Part-time employment: Blueprint Medicines Corporation. M. Roche: Honoraria (self): Epizyme; Shareholder/Stockholder/Stock options, Full/Part-time employment: Blueprint Medicines Corporation. S. Bauer: Research grant/Funding (self): Incyte; Research grant/Funding (self): Novartis; Honoraria (self), Research grant/Funding (self): Blueprint Medicines Corporation; Honoraria (self): Deciphera Pharmaceuticals; Honoraria (self): Bayer; Honoraria (self): Exelixis; Honoraria (self): Novartis; Honoraria (self): PharmaMar; Honoraria (self): ADC Therapeutics; Honoraria (self): Nanobiotix; Honoraria (self): Lilly; Honoraria (self): Daiichi-Sankyo; Honoraria (self): Plexxiko; Honoraria (self): Exelixis; Honoraria (self): Janssen. All other authors have declared no conflicts of interest.
116MO - Efficacy, safety, and quality of life (QoL) with futibatinib in patients (pts) with intrahepatic cholangiocarcinoma (iCCA) harboring FGFR2 fusions/rearrangements: FOENIX-CCA2 (ID 650)
- Junji Furuse (Tokyo, Tokyo, Japan)
Abstract
Background
iCCA has a poor prognosis and its incidence is higher in Asian vs Western countries. Futibatinib is an oral, highly selective, irreversible FGFR1–4 inhibitor that demonstrated safety and preliminary efficacy in pts with iCCA harboring FGFR2 aberrations. This study evaluated safety, efficacy, and QoL with futibatinib treatment in pts with iCCA and FGFR2 fusions/rearrangements.
Methods
FOENIX-CCA2 (NCT02052778), a global phase II study, enrolled pts with unresectable/metastatic iCCA harboring an FGFR2 fusion/rearrangement and disease progression after ≥1 line of systemic therapy (including gemcitabine–cisplatin) but no prior FGFR inhibitors. Pts received futibatinib 20 mg once daily until disease progression/intolerability. The primary endpoint was objective response rate (ORR) per independent central radiology review and RECIST v1.1; secondary endpoints were disease control rate (DCR), duration of response (DOR), progression-free survival (PFS), safety, and patient-reported outcomes (PROs). ORRs of subgroups by baseline demographic, fusion partner, and other molecular alteration (eg, TP53) were also determined.
Results
Of 103 enrolled pts, planned interim data are reported for 67 pts (54% white, 24% Asian) with ≥6 mo of follow-up; 55% of pts received ≥2 prior therapy lines, and 82% had tumors harboring an FGFR2 fusion (BICC1, n=15). ORR was 37.3%, DCR was 82.1%, and median DOR was 8.3 mo. Objective responses occurred regardless of baseline characteristic (subgroup: ≥65 y, ORR: 57.1%), FGFR2 fusion partner (BICC1, 33.3%), or other genetic mutation (TP53, 16.7%). Median PFS was 7.2 mo. The most common treatment-related adverse events (TRAEs; any grade/grade 3) were hyperphosphatemia (81%/27%), diarrhea (37%/0%), and dry mouth (33%/0%); no grade 4–5 TRAEs occurred. TRAEs were managed with dose interruption/reduction (55%/51%); only 1 pt discontinued due to a TRAE. PROs were stable through 273 days (13 cycles) of treatment.
Conclusions
Futibatinib resulted in durable objective responses in pts with iCCA and FGFR2 fusions/rearrangements, including within pt subgroups. Adverse events were manageable, and QoL was maintained.
Clinical trial identification
NCT02052778; EudraCT: 2013-004810-16.
Editorial acknowledgement
Medical writing and editorial assistance were provided by Kelly M. Fahrbach, PhD, and Jennifer Robertson, PhD, of Ashfield Healthcare Communications and funded by Taiho Oncology.
Legal entity responsible for the study
Taiho Oncology, Inc., and Taiho Pharmaceutical Co., Ltd.
Funding
Taiho Oncology, Inc., and Taiho Pharmaceutical Co., Ltd.
Disclosure
J. Furuse: Honoraria (self), Research grant/Funding (self), during the conduct of the study: Taiho Pharmaceutical; Research grant/Funding (self): J-Pharma; AstraZeneca; Bayer; NanoCarrier; Honoraria (self), Research grant/Funding (self): Ono Pharmaceutical; MSD; Sumitomo Dainippon; Yakult Honsha; Daiichi Sankyo; Eisai; Pfizer; Kyowa Hakko Kirin; Chugai Pharma; Sanofi; Takeda; Mochida Pharmaceutical; Eli Lilly Japan; Research grant/Funding (self): Astellas Pharma; Honoraria (self): Novartis; Honoraria (self): Teijin Pharma; Shionogi; EA Pharma; Nihon Servier; Fujifilm Toyama Chemical; Nobel Pharma; Sawai Pharmaceutical; Merck Serono; Nippon Kayaku; Shire; Bayer Yakuhin. L. Goyal: Advisory/Consultancy: Agios; Alentis Therapeutics; AstraZeneca; Honoraria (self), Advisory/Consultancy: Debiopharm Group; Advisory/Consultancy: H3 Biomedicine; Klus Pharma; QED Therapeutics; Honoraria (self), Advisory/Consultancy, Research grant/Funding (self): Taiho Pharmaceutical. F. Meric-Bernstam: Advisory/Consultancy, Research grant/Funding (self): Genentech; Advisory/Consultancy: Inflection Biosciences; Pleris Pharmaceuticals; Clearlight Diagnostics; DarwinHealth; Samsung Bioepis; Spectrum Pharmaceuticals; Aduro Biotech; Origimed; Xencor; Advisory/Consultancy, Research grant/Funding (self): Debiopharm Group; Advisory/Consultancy: Mersana; Honoraria (self), Advisory/Consultancy, Research grant/Funding (self): Seattle Genetics; Advisory/Consultancy: Silverback Therapeutics; Advisory/Consultancy: Immunomedics; Advisory/Consultancy: IBM Watson Health; Advisory/Consultancy: Roche; Advisory/Consultancy: PACT Pharma; Advisory/Consultancy, Research grant/Funding (self): eFFECTOR Therapeutics; Honoraria (self), Research grant/Funding (self): Taiho Pharmaceutical; Honoraria (self): Beth Israel Deaconess Medical Center; Honoraria (self): Sumitomo Group; Honoraria (self): Dialectica; Research grant/Funding (self): Novartis; Research grant/Funding (self): AstraZeneca; Research grant/Funding (self): Calithera Biosciences; Research grant/Funding (self): Bayer; Research grant/Funding (self): Aileron Therapeutics; Research grant/Funding (self): Puma Biotechnology; Research grant/Funding (self): CytomXTherapeutics; Research grant/Funding (self): Jounce Therapeutics; Research grant/Funding (self): Zymeworks; Research grant/Funding (self): Curis; Research grant/Funding (self): Pfizer; Research grant/Funding (self): AbbVie; Research grant/Funding (self): Boehringer Ingelheim; Research grant/Funding (self): Guardant Health; Research grant/Funding (self): Daiichi Sankyo; Research grant/Funding (self): GlaxoSmithKline. A. Hollebecque: Honoraria (self), Research grant/Funding (self), Non-remunerated activity/ies: Incyte; Honoraria (self): Amgen; Honoraria (self): Merck Serono; Honoraria (self): Eisai; Non-remunerated activity/ies: Servier; Non-remunerated activity/ies: Lilly. J.W. Valle: Advisory/Consultancy: Ipsen; Advisory/Consultancy: Novartis; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Merck; Advisory/Consultancy: Delcath Systems; Advisory/Consultancy: Agios; Honoraria (self), Advisory/Consultancy: Pfizer; Advisory/Consultancy: PCI Biotech; Advisory/Consultancy: Incyte; Advisory/Consultancy: Keocyt; Advisory/Consultancy: QED Therapeutics; Advisory/Consultancy: Pleris Pharmaceuticals; Advisory/Consultancy: Genoscience Pharma; Advisory/Consultancy: Mundipharma EDO GmbH; Advisory/Consultancy: Wren Laboratories; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: Nucana; Advisory/Consultancy: Servier; Advisory/Consultancy: Debiopharma Group; Advisory/Consultancy, Speaker Bureau/Expert testimony: Imaging Equipment Limited; Speaker Bureau/Expert testimony, Research grant/Funding (self): Novartis; Honoraria (self), Speaker Bureau/Expert testimony: Ipsen; Honoraria (institution): Celgene. C. Morizane: Research grant/Funding (self): Ono Pharmaceutical; Research grant/Funding (self): Merck; Research grant/Funding (self): Eisai; Honoraria (self), Research grant/Funding (self): Taiho Pharmaceuticals; Honoraria (self), Research grant/Funding (self): Yakult Honsha; Honoraria (self), Research grant/Funding (self): MSD; Honoraria (self), Research grant/Funding (self): J-Pharma; Honoraria (self), Research grant/Funding (self): AstraZeneca; Honoraria (self): Teijin Pharma; Honoraria (self): Novartis; Honoraria (self): AbbVie. T.B. Karasic: Research grant/Funding (self): Syndax; Research grant/Funding (self): Taiho Pharmaceutical; Research grant/Funding (self): Celgene; Research grant/Funding (self): H3 Biomedicine; Research grant/Funding (self): Bristol-Myers Squibb; Research grant/Funding (self): Lilly; Research grant/Funding (self): Sirtex Medical. R.K. Kelley: Research grant/Funding (institution): Taiho Pharmaceutical; Agios; Adaptimmune; AstraZeneca; Bayer; Bristol-Myers Squibb; Eli Lilly; EMD Serono; Exelixis; Merck; Partner Therapeutics; QED Therapeutics; Novartis; Non-remunerated activity/ies: Ipsen; Honoraria (self): Genentech/Roche; Honoraria (self): Gilead. P.A. Cassier: Non-remunerated activity/ies, During the conduct of the study: Taiho Pharmaceutical; Honoraria (self), Non-remunerated activity/ies: AstraZeneca; Non-remunerated activity/ies: AbbVie; Non-remunerated activity/ies: Bayer; Non-remunerated activity/ies: Bristol-Myers Squibb; Honoraria (self), Non-remunerated activity/ies: Blueprint; Honoraria (self), Non-remunerated activity/ies: Merck Serono; Non-remunerated activity/ies: GlaxoSmithKline; Non-remunerated activity/ies: Janssen; Non-remunerated activity/ies: Lilly; Honoraria (self), Research grant/Funding (self), Non-remunerated activity/ies: Novartis; Honoraria (self), Non-remunerated activity/ies: Roche/Genentech. H-J. Klumpen: Research grant/Funding (self): Bayer; Non-remunerated activity/ies: Ipsen. N. Uboha: Non-remunerated activity/ies: Taiho Pharmaceutical; Non-remunerated activity/ies: AstraZeneca; Non-remunerated activity/ies: Eli Lilly; Non-remunerated activity/ies: EMD Serono; Non-remunerated activity/ies: Incyte; Non-remunerated activity/ies: Ipsen. E. Mitchell: Honoraria (self), Research grant/Funding (self): Exelixis; Honoraria (self), Research grant/Funding (self): Genentech; Honoraria (self): Bristol-Myers Squibb; Honoraria (self): Merck; Honoraria (self): Novartis. Y. He, K.A. Benhadji: Full/Part-time employment: Taiho Pharmaceutical. J.A. Bridgewater: Honoraria (self): Taiho Pharmaceutical. All other authors have declared no conflicts of interest.
117MO - Comparison of survival and patterns of recurrence in gastric neuroendocrine carcinoma, mixed adenoneuroendocrine carcinoma and adenocarcinoma: A multicenter study from China (ID 472)
- Jun-Peng Lin (Fuzhou, China)
Abstract
Background
Gastric neuroendocrine carcinoma (G-NEC) and mixed adenoneuroendocrine carcinoma (G-MANEC) are rare pathological types of gastric cancer, and there is a lack of multicenter studies comparing the prognosis and recurrence patterns of G-NEC, G-MANEC and gastric adenocarcinoma (G-AC).
Methods
Patients with resectable G-NEC and G-MANEC at 23 hospitals in China from January 2006 to December 2016 were identified. In addition, 2,785 patients with G-AC were selected as controls. Propensity score-matched analysis was used to match stage among the different pathological types, and disease-free survival (DFS), postrecurrence survival (PRS) and patterns of recurrence were examined.
Results
We reviewed 3,689 patients: 503 of with G-NEC, 401 with G-MANEC and 2,785 with G-AC. After propensity score matching, the DFS and PRS of G-NEC and G-MANEC were significantly worse than those of G-AC (all P<0.05). Multivariable analyses revealed that G-NEC and G-MANEC (vs. G-AC) were independent risk factors for DFS and PRS (all P<0.05). Compared with G-AC patients, G-NEC and G-MANEC patients were more likely to have distant recurrence (P<0.05). On multivariate analysis, G-NEC and G-MANEC were independent predictors for distant recurrence (both P<0.001). Additionally, T3-T4 stage and lymph node metastasis were independent risk factors for distant recurrence of G-NEC and G-MANEC (both P<0.05).
Conclusions
G-NEC and G-MANEC have worse prognoses and are more prone to distant recurrence than G-AC. Thus, different follow-up and treatment strategies should be developed for G-NEC and G-MANEC, especially patients with tumors penetrating into the subserosa or deeper layers and with lymph node metastasis.
Legal entity responsible for the study
The authors.
Funding
Scientific and Technological Innovation Joint Capital Projects of Fujian Province.
Disclosure
All authors have declared no conflicts of interest.
118MO - Circulating tumour DNA methylation are markers for early detection of pancreatic ductal adenocarcinoma (PDAC) (ID 957)
- Xiaoding Liu (Beijing, China)
Abstract
Background
PDAC is a cancer of high mortality and low survival. Its early detection is critical due to symptoms often occur only at advanced stages. However, there is no reliable screening tool to identify high-risk patients. ctDNA methylation has recently emerged as a promising new target to differentiate PDAC plasma from normal plasma for its early detection.
Methods
Reduced representation bisulfite sequencing libraries were made in 46 PDAC tissues, 30 para-PDAC tissues and 20 PDAC plasmas to screen PDAC-specific markers, which was done by quantifying and comparing methylation levels of genomic regions and individual CpG sites between those groups. Markers were validated in plasma samples from 84 PDAC patients and 64 normal controls to propose a blood classifier. The best-performing markers were developed into a targeted sequencing panel, which was tested on a larger collection of plasma samples from patients of a variety of pancreatic diseases to build and validate a PDAC-predicting model.
Results
We profiled genome-wide methylation patterns of tissues samples to identify 171 PDAC-specific markers. We reiterated training and cross-validating PDAC classification models using SVM method and achieved an average sensitivity of 86% and specificity of 88%. To prove the feasibility of a non-invasive detection in plasma, a targeted methylation assay using those markers was tested on PDAC and normal plasmas and yielded an average sensitivity of 68.4% and a specificity of 85.8%. We refined the panel by selecting the most discriminatory markers and built a smaller panel for a more efficient target capture, which is validated in an independent cohort of 200 plasma samples that included PDAC, chronic pancreatitis (CP) and normals from multiple centers. The smaller panel achieved an AUC above 0.90 when classifying PDAC from normals, and an AUC of 0.88 when separating PDAC from CPs.
Conclusions
We have developed an NGS based target assay covering PDAC-specific DNA methylation targets by screening and validation on PDAC tissues and plasmas. It has shown encouraging results to classify PDAC plasma from non-malignant diseases, demonstrating its potential to be optimized into non-invasive diagnostics for blood-based early PDAC screening.
Legal entity responsible for the study
Peking Union Hospital.
Funding
Intergovernmental Cooperation Fund of China Science and Technology Exchange Center.
Disclosure
Q. He, Z. Su: Shareholder/Stockholder/Stock options, Full/Part-time employment: Singlera Genomics. C. Ma, Z. Xie: Full/Part-time employment: Singlera Genomics. R. Liu: Leadership role, Shareholder/Stockholder/Stock options, Full/Part-time employment: Singlera Genomics. All other authors have declared no conflicts of interest.
Invited Discussant abstracts 115MO, 116MO, 117MO and 118MO (ID 1085)
- David Tai (Singapore, Singapore)
LIVE Q&A (ID 1086)
- Li-Tzong Chen (Tainan City, Taiwan)
119MO - Application of an artificial neural network for predicting the chemotherapy benefit of patients with gastric cancer after radical surgery (ID 690)
- Zhen Xue (Fuzhou, China)
Abstract
Background
Artificial neural network (ANN) models have a strong self-learning ability and can deal with complex biological information, but there is no ANN model for predicting the benefits of adjuvant chemotherapy in patients with gastric cancer (GC).
Methods
The clinicopathological data of patients who underwent radical resection of GC from January 2010 to September 2014 were analyzed retrospectively. Patients who underwent surgery combined with adjuvant chemotherapy were randomly divided into a training cohort (70%) and a validation cohort (30%). An ANN model (CT-benefit-ANN) was established, and its ability to predict the benefit of chemotherapy was evaluated by the C-index. The prognostic prediction and stratification ability of CT-benefit-ANN and the 8th AJCC staging system were compared by ROC curves and Kaplan-Meier curves.
Results
In the training and validation cohort, CT-benefit-ANN both shows good prediction accuracy for adjuvant chemotherapy benefit. The ROC curve showed that the prediction accuracy of CT-benefit-ANN was better than that of the 8th AJCC staging system in all groups. The calibration plots showed that the predicted prognosis of CT-benefit-ANN was highly consistent with the actual value. The survival curves showed that CT-benefit-ANN could stratify prognosis well for all groups and performed significantly better than the 8th AJCC staging system.
Conclusions
The CT-benefit-ANN model developed in this study can accurately predict the benefits of adjuvant chemotherapy in patients with stage II/III GC. The benefit score based on CT-benefit-ANN can predict the long-term prognosis of patients with adjuvant chemotherapy and has good prognostic stratification ability.
Legal entity responsible for the study
The authors.
Funding
Scientific and Technological Innovation Joint Capital Projects of Fujian Province.
Disclosure
All authors have declared no conflicts of interest.
120MO - A phase II study of trifluridine/tipiracil and ramucirumab in patients with unresectable advanced or recurrent gastric cancer (ID 516)
- Takayuki Ando (Toyama, Japan)
Abstract
Background
Trifluridine/tipiracil improved overall survival in patients previously treated for advanced gastric cancer (AGC) in a phase III study. Survival benefit of ramucirumab, an anti-VEGFR2 antibody, was shown in patients pretreated for AGC. We conducted a phase II study to assess the efficacy and safety of trifluridine/tipiracil plus ramucirumab in patients pretreated for AGC.
Methods
This study was an open-label, single-arm, two-cohort, phase II study. Patients with pathologically confirmed unresectable AGC or gastroesophageal junction adenocarcinoma were enrolled. Cohort A included patients previously treated with one line of chemotherapy without ramucirumab, and cohort B included patients previously treated with 2–4 lines of chemotherapy including ramucirumab. Patients received trifluridine/tipiracil 35 mg/m2 orally twice daily on days 1–5 and days 8–12 of each 28-day cycle, plus intravenous ramucirumab 8 mg/kg on days 1 and 15. The primary endpoint was disease control rate (DCR) assessed by each investigator. The secondary endpoints were overall response rate (ORR), progression-free survival (PFS), time to treatment failure, time to deterioration of ECOG PS, and safety. The sample size was 30 patients for each cohort assuming the point estimate of DCR to exceed the threshold (cohort A: 60%, B: 40%) by 15% with a probability of ≥90%.
Results
From April to October 2019, 64 patients were enrolled in Japan and included for efficacy and safety analyses (cohort A: 33 patients, B: 31 patients). In cohort A and cohort B, DCR was 84.8% (95% confidence interval [CI], 68.1–94.9) and 77.4% (95% CI, 58.9–90.4), ORR was 9.1% and 16.1%, and median PFS was 5.9 months and 5.3 months, respectively. Frequently reported adverse events of grade 3 or worse in cohorts A and B were neutropenia (81.8% and 74.2%), leukopenia (24.2% and 22.6%), thrombocytopenia (24.2% and 12.9%), anaemia (18.2% and 19.4%) and decreased appetite (12.1% and 3.2%), respectively. There was no treatment-related death.
Conclusions
Trifluridine/tipiracil plus ramucirumab showed clinical activity and an acceptable safety profile in patients previously treated for AGC with or without previous ramucirumab exposure.
Clinical trial identification
JapicCTI-194596.
Legal entity responsible for the study
Taiho Pharmaceutical Co., Ltd.
Funding
Taiho Pharmaceutical Co., Ltd., and Eli Lilly and Company.
Disclosure
T. Ando: Research grant/Funding (institution): Eli Lilly Japan; Otsuka Pharmaceutical Co; Chugai Pharmaceutical Co; Bayer Yakuhin. A. Kawazoe: Honoraria (self), Research grant/Funding (institution): Taiho; Ono; Research grant/Funding (institution): MSD; Sumitomo Dainippon Pharma. H. Hosaka: Research grant/Funding (institution): Taiho Pharmaceutical. K. Amagai: Research grant/Funding (institution): MSD; Taiho Pharmaceutical; Nippon Zoki Pharmaceutical; Daiichi-Sankyo; Hisanitsu Pharmaceutical. K. Fujitani: Honoraria (self): Eli Lilly; Taiho. K. Ogata, Y. Yamamoto: Full/Part-time employment: Taiho. K. Shitara: Honoraria (self), Advisory/Consultancy: Novartis; 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, Research grant/Funding (institution): Taiho Pharmaceutical; Advisory/Consultancy, Research grant/Funding (institution): MSD; Advisory/Consultancy: GlaxoSmithKline; Research grant/Funding (institution): Chugai Pharmaceutical; Research grant/Funding (institution): Medi Science; Research grant/Funding (institution): Daiichi Sankyo; Research grant/Funding (institution): Dainippon Sumitomo Pharma. All other authors have declared no conflicts of interest.
121MO - ctDNA and prognosis in resected esophageal adenocarcinoma (EAC) (ID 719)
- Emma Ococks (Cambridge, United Kingdom)
Abstract
Background
Relapse after chemotherapy and surgery occurs in >50% of resected EAC patients (pts). ctDNA following resection is prognostic in multiple cancers, however false positive results due to clonal haematopoiesis of indeterminate potential (CHIP) may limit the accuracy of tumour-naive ctDNA panels. We investigated the prognostic value post-surgical ctDNA in resected EAC and optimised a pipeline to reduce the effect of CHIP.
Methods
Pts were identified from the prospective national UK OCCAMS consortium dataset. A 77 gene tumour naïve ctDNA panel was deployed. Plasma samples were sequenced to a mean depth of 7,062x (range: 2,196 – 28,524). Pipeline optimisation included: removal of variants which were synonymous, >0.05% frequency across germline databases; those which fall in untranslated or upstream gene regions and variants at >5% VAF if always confirmed as germline in COSMIC. Post-op ctDNA +ve is defined as at least 2 variants detected in the same sample. Overall survival (OS) and disease-free survival (DFS) was estimated using the Kaplan-Meier method and compared using the log-rank test.
Results
97 pts were identified; 83/97 (86%) male, median age 68 years (SD 9.5 years), 100% cT3/T4, 75% cN+. 96/97 (99.0%) had neoadjuvant chemotherapy. 78/97 (80.4%) had CHIP analyses; 18/78 (23.1%) had CHIP variants removed. Using stringent quality criteria 16/79 (20.3%) were ctDNA +ve post-resection; recurrence was observed in 12/16 (75.0%) of these. Median OS for ctDNA +ve pts 14.9 months (m) vs 29.5m for ctDNA -ve (HR 2.32, (95% CI 1.14- 4.73, p = 0.03). When CHIP was excluded 10/63 (16.9%) pts were ctDNA +ve and 9/10 of these (90.0%) recurred. With correction for CHIP median OS ctDNA +ve pts was 10.1m vs 29.5m ctDNA -ve. (HR 5.55, (95% CI 2.42- 12.71, p = 0.0003). One pt with short follow-up due to recent treatment (30 weeks) who was ctDNA +ve has not yet relapsed. Similar outcomes were observed for DFS.
Conclusions
We demonstrate in a large, national, prospectively collected dataset that the ctDNA in plasma following surgery for EAC is prognostic for relapse. Pipeline optimisation can reduce or eliminate false positives from CHIP. In future, post-operative ctDNA could be used to risk stratify patients into high and low risk groups for intensification or de-escalation of adjuvant chemotherapy.
Legal entity responsible for the study
The authors.
Funding
Roche.
Disclosure
E. Ococks: Travel/Accommodation/Expenses: Roche. R. Fitzgerald: Advisory/Consultancy, Shareholder/Stockholder/Stock options: Cyted Ltd.; Licensing/Royalties: Cytosponge; Research grant/Funding (self): Roche; Research grant/Funding (self): AstraZeneca. E. Smyth: Honoraria (self): Zymeworks; Honoraria (self): Astellas; Honoraria (self): AstraZeneca; Honoraria (self): Bristol-Myers Squibb; Honoraria (self): Merck; Honoraria (self): Celgene; Honoraria (self): Five Prime; Honoraria (self): Gritstone Oncology; Honoraria (self): Servier. All other authors have declared no conflicts of interest.
Invited Discussant abstracts 119MO, 120MO and 121MO (ID 1087)
- Do-Youn Oh (Seoul, Korea, Republic of)
LIVE Q&A (ID 1088)
- Li-Tzong Chen (Tainan City, Taiwan)