bluuebunny/crossref_metadata_2025 huggingface dataset:
Pathway analysis of hypoxia-related factors in early colorectal cancer patients with poor prognosis.
Authors: Tan Yingxin , Rong Yuming , Yu Zhaoliang , Gao Feng , Chen Yufeng , Lin Xutao , Zou Yifeng , Chen Xi
Published: May 2019

3613

Background: Colorectal cancer is one of the most common malignancies with a high mortality rate. Patients with stage I and stage II colorectal cancer have limited options for treatment. Hypoxia affects the activation and regulation of colorectal cancer cells and participates in its invasion and migration. However, there is lack of an accurate and non-invasive method for assessing tumor hypoxia. The aim of this study was developing and validating a hypoxia gene signature for predicting the outcome in stage I/II colorectal cancer patients. At the same time , we hypothesized that analysis of database of CIT microarray dataset could identify important biomarkers for stage I/II colorectal cancer patients. Methods: A total of 309 colorectal cancer patients of early stage with complete clinical information were enrolled for construction generation of hypoxia-related gene signature (HRGS) based on the CIT microarray dataset. 1877 colorectal cancer patients with complete prognostic information in 5 independent datasets were divided into a training cohort and two validation cohort (TCGA and meta-validation). Prognostic analysis was assessed in these cohort to evaluate the predictive value of HRGS. Results: A model of prognostic HRGS containing 14 hypoxia-related genes was developed. In training cohort and two validation cohorts, patients in hypoxia high-risk group satisfied by our HRGS had significant poor disease free survival compared with those in the in the low risk group (HR=4.35, 95% CI=2.30-8.23, P<0.001 in training cohort, HR=2.14, 95% CI=1.09-4.21, P=0.024 in TCGA cohort, HR=1.91, 95% CI=1.08-3.39, P=0.024 in meta-validation cohort). When compared with Oncotype DX, HRGS achieved an improved survival correlation in the training cohort (mean C-index, 0.80 vs 0.65, P<0.05) and the validation cohort (mean C-index, 0.70 vs 0.61 in the TCGA cohort, mean C-index, 0.68 vs 0.73 in the meta-validation cohort). Analysis of the data found that patients with low survival rates have significant relationships with genes regulated by the cell cycle pathway, such as mTROC1, E2F, G2-M, mitotic, oxidative phosphorylation, MYC, PI3K-AKT-mTOR (P<0.005). Conclusions: HRGS was a satisfactory prognostic prediction model for early stage colorectal patients. Hypoxia-related genes that regulate the cell cycle pathway were associated with prognosis in patients with stage I and stage II colorectal cancer. Further researches are needed to assess the clinical effectiveness of the system and the treatment options for biological targets.
ABC-06 | A randomised phase III, multi-centre, open-label study of active symptom control (ASC) alone or ASC with oxaliplatin / 5-FU chemotherapy (ASC+mFOLFOX) for patients (pts) with locally advanced / metastatic biliary tract cancers (ABC) previously-treated with cisplatin/gemcitabine (CisGem) chemotherapy.
Authors: Lamarca Angela , Palmer Daniel H. , Wasan Harpreet Singh , Ross Paul J. , Ma Yuk Ting , Arora Arvind , Falk Stephen , Gillmore Roopinder , Wadsley Jonathan , Patel Kinnari , Anthoney Alan , Maraveyas Anthony , Waters Justin S. , Hobbs Claire , Barber Safia , Ryder David , Ramage John , Davies Linda M , Bridgewater John A. , Valle Juan W. ,   on behalf of the Advanced Biliary Cancer (ABC) Working Group
Published: May 2019

4003

Background: Level A evidence supports use of CisGem as first-line chemotherapy for ABC; no robust evidence is available for second-line chemotherapy. Methods: Pts diagnosed with ABC with disease progression after prior CisGem were randomised (1:1) to either ASC+mFOLFOX or ASC. Randomisation was stratified by serum albumin levels ( < 35 vs ≥35 g/L), platinum sensitivity (determined from first-line CisGem) and disease extent (locally advanced vs metastatic). Pts with ECOG PS0-1, adequate haematological, renal and liver function, and adequate biliary drainage were eligible. Primary end-point was overall survival (OS) (multivariable Cox regression adjusted for stratification factors); sample size: 162 pts delivering 148 events were required (80% power; 5% two-sided alpha) for a hypothesised hazard ratio (HR) of 0.63. Assumed median survival for ASC was 4 months. Results: 162 pts (81 in each arm) were randomised (27 March ‘14 - 04 Jan ‘18); median age 65 yrs (range 26-84); sex: 80 (49%) male, 82 (51%) female; primary site: intrahepatic 72 (44%), extrahepatic 45 (28%), gallbladder 34 (21%) and ampullary 11 (7%). Baseline characteristics were balanced between arms except platinum sensitivity (ASC+mFOLFOX 27 pts (33%); ASC 34 pts (42%)). After 150 OS events, the adjusted HR was 0.69 (95% CI 0.50-0.97; p = 0.031; ASC+mFOLFOX vs ASC). Median OS (months (m)), 6m and 12m OS-rate (%) were 6.2m, 50.6% and 25.9% for the ASC+mFOLFOX and 5.3m, 35.5%, 11.4% for the ASC arm, respectively. Grade 3/4 toxicities were reported in 48 (59%) and 32 (39%) pts in the ASC+mFOLFOX and ASC arm, respectively; these were balanced between arms except for fatigue and neutropenia (more frequent in ASC+mFOLFOX arm); data cleaning is ongoing. No chemotherapy-related deaths were reported. Conclusion: Survival with ASC was greater than assumed; ASC+mFOLFOX improved OS after progression to CisGem with a clinically meaningful increase in 6m and 12m OS rate. ASC+mFOLFOX should become standard of care in second-line for ABC. Clinical trial information: NCT01926236.
PET-directed combined modality therapy for gastroesophageal junction cancer: First results of the prospective MEMORI trial.
Authors: Lorenzen Sylvie , Quante Michael , Rauscher Isabel , Slotta-Huspenina Julia , Becker Karl Friedrich , Weichert Wilko , Feith Marcus , Friess Helmut , Combs Stephanie E , Weber Wolfgang , Haller Bernhard , Angele Martin K , Albertsmeier Markus , Blankenstein Christiane , Kasper Stefan , Zimmermann Jens Peter , Algül Hana , Schmid Roland M. , Schwaiger Markus , Siveke Jens T
Published: May 2019

4018

Background: We evaluated a PET-guided treatment stratification for improvement in obtaining negative surgical margins (R0) in resectable gastroesophageal junction (GEJ) adenocarcinoma. According to sequential 18F-FDG PET, only 40–50% of patients (pts) respond to neoadjuvant chemotherapy (CTX). Early PET non-responders (P-NR) after induction CTX might benefit from changing to chemoradiation (CRT). Methods: 75 pts with resectable GEJ adenocarcinomas were enrolled in this interventional, prospective, non-randomized multicenter trial. Pts underwent baseline 18F-FDG PET scan followed by 1 cycle of CTX (physicians’ choice, e.g. EOX, XP, mFOLFOX6). PET was repeated at day 14-21 and responders (P-R), defined as ≥ 35% decrease in SUVmax from baseline, continued with CTX. P-NR switched to CRT (41.4 Gy/23 fractions with weekly carboplatin/paclitaxel). Pts underwent surgery 4-6 weeks post-CTX/CRT. Primary objective was an improvement of R0 resection rates in P-NR above a proportion of 70% based on results from the MUNICON1/2 trials. Secondary endpoints include disease-free survival (DFS), overall survival (OS), measured from randomization to death from any cause, and translational endpoints. Results: Between 12/2014 and 07/ 2018 160 pts with resectable GEJ adenocarcinomas were prospectively screened with PET in three German university centers. Overall, 85 pts (53%) could not be included due to previously undetectable metastases (40/25%), no or too low FDG uptake of the primary tumor (21/13%), other reasons (24/15%). 75 eligible pts were enrolled in the study and 69 were evaluable. Based on PET criteria, 47 (68%) and 22 (32%) were P-R and P-NR, respectively. R0 resection rates were 94% (44/47) for P-R and 91% (20/22) for P-NR. Pathologic complete remission (pCR; < 10% vital tumor cells), was 33% (15/46) in P-R and 55% (12/22) in P-NR. With a median follow-up time of 19 months (mo), estimated 18 mo DFS was 71%/61% for P-R/P-NR, respectively. Observed median 18 mo OS was 95% for P-R and 75% for P-NR. Conclusions: Alternative CRT for GEJ adenocarcinoma improved R0- and pCR rates among pts who were P-NR after induction CTX. PET response was prognostic for a prolonged OS and DFS. Clinical trial information: 2014-000860-16.
Randomized phase III trial of laparoscopy-assisted versus open distal gastrectomy with nodal dissection for clinical stage IA/IB gastric cancer (JCOG0912).
Authors: Katai Hitoshi , Mizusawa Junki , Katayama Hiroshi , Morita Shinji , Yamada Takanobu , Bando Etsuro , Misawa Kazunari , Takagi Masakazu , Takagane Akinori , Teshima Shin , Koeda Keisuke , Nunobe Souya , Yoshikawa Takaki , Terashima Masanori , Sasako Mitsuru ,   Stomach Cancer Study Group of Japan Clinical Oncology Group
Published: May 2019

4020

Background: The number of patients undergoing laparoscopy-assisted distal gastrectomy (LADG) has been increasing worldwide. Several retrospective studies have demonstrated equivalent survival after LADG compared to open distal gastrectomy (ODG). However, no confirmatory randomized controlled trials has been published in a peer review journal to evaluate the efficacy of LADG compared with ODG, ensuring strict surgical skill and quality control of surgery. We conducted phase III study to confirm that LADG is not inferior to ODG in efficacy. Methods: Eligibility criteria included histologically proven adenocarcinoma in the middle or lower third of the stomach; clinical stage I tumor (T1N0, T1N1, T2(MP)N0). Patients were preoperatively randomized to ODG or LADG. LADG was performed by accredited surgeon. The extent of nodal dissection was decided according to Japanese gastric cancer treatment guidelines. The primary endpoint is relapse-free survival (RFS) and the secondary endpoints are overall survival (OS), short-term clinical outcomes, and postoperative quality of life. Planned sample size was 920 patients in total, which was determined with at least 80% power, a one-sided alpha of 5%, and a non-inferiority margin for a hazard ratio of 1.54. Before the 1st interim analysis, the primary endpoint was amended from OS to RFS in 2015 because the surrogacy of RFS for OS was demonstrated and the predicted number of events for OS was smaller than expected. Results: A total of 921 patients were randomized (ODG 459, LADG 462) between Mar. 2010 and Nov. 2013. Among 921 patients, 912 patients (99%) underwent assigned surgery. Conversion to ODG was needed for 16 patients (3.5%) in LADG arm mainly due to advanced disease. 5-year RFS was 94.0% (95% CI: 91.4-95.9%) in ODG and 95.1% (92.7-96.8%) in LADG. LADG was non-inferior to ODG for RFS. (HR: 0.84 [90% CI: 0.56-1.27 ( < 1.54)], p for non-inferiority = 0.008). 5-year OS was 95.2% (92.7-96.8) in ODG and 97.0% (94.9-98.2) in LADG (HR: 0.83 [95% CI: 0.49-1.40]). Conclusions: The non-inferiority of LADG to ODG in RFS was confirmed. LADG has been established as one of the standard treatments for clinical stage I gastric cancer. Clinical trial information: UMIN000003319.
Perioperative chemotherapy alone versus preoperative chemoradiotherapy for locally advanced distal esophageal and gastroesophageal junction cancer: A 10-year review of the British Columbia (BC) Cancer Registry.
Authors: Liu Shiru Lucy , Yu Irene S. , Lau Sally CM , Zhao Yizhou , Schellenberg Devin , Gill Sharlene , Lim Howard John
Published: May 2019

4028

Background: The optimal treatment strategy for resectable cancer of the distal esophagus (ESOPH) and gastroesophageal junction (GEJ) remains controversial. This study evaluates patterns of practice in BC, rates of complete surgical resection, and survival outcomes of patients treated with perioperative chemotherapy alone (CA), per MAGIC or FLOT4 protocol, versus preoperative chemoradiotherapy (CRT), per CROSS protocol. Methods: We undertook a provincial analysis of initially resectable, locally advanced, cancer of the ESOPH and/or GEJ who underwent surgery in BC, from 2008 to 2018. Baseline patient, tumor, treatment, and clinical outcome data were collected from the BC Cancer Registry. Kaplan-Meier survival and multivariate regression analyses were conducted. Results: Among 575 patients, 468 underwent surgery and were included (Table). More surgeries were aborted intraoperatively in the CA cohort compared to CRT (12% vs 2%, p<0.001). There was no difference in age, sex, or ECOG performance status among the cohorts, and 83% were adenocarcinoma. While 82% of ESOPH involving GEJ (N = 251, 54%) is treated with CRT, only 53% of GEJ alone (N=217, 46%) is treated with CRT (p<0.001). CRT is associated with a higher rate of complete or partial pathologic response compared to CA (59% vs 39%, p=0.002). R0 resection rate was 90% and 94% in the CA and CRT cohort, respectively (p=0.383). There is no statistically significant difference in overall survival, with medians of 29.6 and 26.0 months for patients treated with CA and CRT, respectively (p=0.723). Cancer-specific survival is also not significantly different (p=0.565). In the CA cohort, 37% of patients complete all 8 cycles of FLOT and 52% of patients complete all 6 cycles of MAGIC (p=0.396). Conclusions: Patients treated with CRT have higher rates of complete resection and pathologic response, but their survival is not significantly different compared to those treated with CA. [Table: see text]
Phase 2 study of camrelizumab (anti-PD-1 antibody) combined with apatinib and chemotherapy for the first-line treatment of advanced esophageal squamous cell carcinoma.
Authors: Zhang Bo , Qi Ling , Wang Xi , Jiang Jun , Zhang Xin , Liu Yun , Mu Lan , Huang Jing
Published: May 2019

4033

Background: Both anti-PD-1 antibodies and molecular antiangiogenic agents have shown promising anti-tumor activities in patients with advanced esophageal cancer. We conducted this single-center phase 2 study to evaluate the efficacy and safety of camrelizumab (anti-PD-1 antibody) plus apatinib (VEGFR2-TKI) in combination with liposomal paclitaxel and nedaplatin in the first-line treatment of patients with esophageal squamous cell carcinoma (ESCC). Methods: Patients with unresectable locally advanced or metastatic ESCC received camrelizumab 200mg d1, liposomal paclitaxel 150mg/m2 d1, nedaplatin 50mg/m2 d1 and apatinib 250mg d1-14. Treatments were repeated every 14 days for up to 6-9 cycles, followed by maintenance therapy with camrelizumab, apatinib, or both. The primary end point was progression-free survival (PFS) in the intention-to-treat population. Secondary end points included objective response rate (ORR), disease control rate (DCR), overall survival (OS) and safety. PD-L1 positivity, defined as a combined positive score (CPS) ≥1, was evaluated by immunohistochemistry (IHC). Results: Between Aug 6th 2018 and Feb 6th 2019, a total of 29 patients were enrolled. The median age was 62 years (43-70). Most patients were male (22/29, 75.9%) with metastatic disease (25/29, 86.2%). Response evaluation by independent central review was available in 26 patients, with 19 achieving a best response of PR, 6 with SD, and 1 with PD. The ORR and DCR were 73.1% (19/26) and 96.2% (25/26), respectively. Data for PFS and OS were not matured. The most common grade 3/4 adverse events were leucopenia (21/29, 72.4%) and neutropenia (15/29, 51.7%). Two cases of treatment-related SAEs occurred, both led to hospitalization: one patient developed grade 3 febrile neutropenia, grade 4 leucopenia and grade 3 anorexia; another patient developed grade 4 toxic epidermal necrolysis. Conclusions: Camrelizumab plus apatinib in combination with liposomal paclitaxel and nedaplatin could be a new treatment option for patients with unresectable locally advanced or metastatic ESCC. Clinical trial information: NCT03603756.
Prognostic value of serum soluble programmed death-ligand 1 (sPDL1) and dynamics during chemotherapy in advanced gastric cancer patients.
Authors: Park Woochan , Bang Ju-Hee , Nam Ah-Rong , Park Ji Eun , Kim Mei Hua , Oh Kyoung Seok , Bang Yung-Jue , Oh Do-Youn
Published: May 2019

4034

Background: The soluble form Programmed Death-Ligand 1(sPDL1) is suggested to have immunosuppressive activity and under investigation as candidate biomarker for immuno-oncology drug development. In this study, we measured the serum sPDL1 at pre-and post-chemotherapy and evaluated its prognostic implication and dynamics during chemotherapy in advanced gastric cancer (GC). Methods: We prospectively enrolled 68 GC patients who were candidates for palliative standard 1st-line chemotherapy, and blood was serially collected at pre-and post-one cycle of chemotherapy, at best response and disease progression. sPDL1 was measured using an enzyme-linked immunosorbent assay. Response to chemotherapy, overall survival (OS), progression-free survival (PFS) and other prognostic factors including neutrophil-lymphocyte ratio (NLR) were obtained. The cut-off values of sPDL1 levels and changes for survivals were found using C-statistics. Results: The median baseline sPDL1 was 0.8ng/mL(range, 0.06 - 6.06ng/mL). The median OS and PFS were 14.9 months (95% CI: 7.33-22.47) and 8.0 months (95% CI: 5.96-10.0), respectively. sPDL1 and NLR showed a positive correlation. Patients with low levels of sPD-L1 at diagnosis ( < 1.92 ng/mL) showed a better OS and PFS than the patients with a high sPDL1 (OS: 18.3 vs. 95 months, P = 0.057, PFS: 8.9 vs. 6.0 months, P = 0.04). The baseline sPDL1 before treatment were higher in the PD group than in the SD and PR groups (mean:2.91, 1.17, 1.19, P = 0.019). Patients whose sPDL1 increased after 1st cycle of chemotherapy showed the tendency of worse PFS and OS. When disease progressed, sPDL1 increased compared with baseline (mean:1.31, 1.45, P = 0.029). Conclusions: sPDL1 at pre-chemotherapy confers the prognostic value for PFS and OS in GC patients under palliative 1st-line chemotherapy. The dynamics of sPDL1 during chemotherapy correlates with disease courses.
POF (paclitaxel plus FOLFOX) versus IP PAC (intraperitoneal paclitaxel plus FOLFOX) versus FOLFOX as a first-line treatment in advanced gastric cancer (AGC): Update from a multicenter, randomized phase II trial, FNF-004 trial.
Authors: Lin Rongbo , Chen Yigui , Zhu Jinfeng , Lin Peicheng , Chen Wujin , Fang Wenzheng , Li Hui , Liu Jie , Zhao Shen , Fan Nan-Feng
Published: May 2019

4035

Background: The PFS with POF was statistically significantly improved and IP PAC was trending to improve compared to FOLFOX in first-line setting in AGC were reported in 2019 ASCO-GI (abstract 6). Update and subgroup analysis were released herein. Methods: The patients with AGC were randomized to three groups. The POF or IP PAC was paclitaxel 135 mg/m2intravenously (POF) or paclitaxel 80 mg/m2 intraperitoneally (IP PAC) followed by mFOLFOX6 omitted 5-Fu bolus. Every 14 days repeated for all three regimens. Up to 9 cycles of treatment were administered, followed by S-1 until disease progression. The primary endpoint was PFS. Results: Between Nov 2015 and May 2018, 89 pts (30 POF, 29 IP PAC, 30 FOLFOX) were randomly allocated. PFS, OS and RR were seen in the table below. Either POF or IP PAC was statistically significantly better than FOLFOX in PFS. In subgroup with female, peritoneal metastasis, ascites, lymphadenopathy in peritoneal cavity, number of organs involved > 2, POF was statistically significantly better than FOLFOX in PFS. In subgroup with female, gastrium of primary tumor site, peritoneal metastasis, ascites, no lymphadenopathy out of peritoneal cavity, IP PAC was statistically significantly better than FOLFOX in PFS. Intravenously docetaxel plus S-1 still saw response after IP PAC. Conclusions: either POF or IP PAC improved survival compared to FOLFOX, especially in patients with female or peritoneum metastasis. Only POF, not IP PAC, improved response rate compared to FOLFOX. Clinical trial information: NCT02845908. [Table: see text]
Health-related quality of life (HRQoL) of pembrolizumab (pembro) versus physician choice single-agent paclitaxel, docetaxel, or irinotecan in subjects with advanced/metastatic adenocarcinoma (ACC) or squamous cell carcinoma (SCC) of the esophagus that has progressed after first-line standard therapy (KEYNOTE-181).
Authors: Adenis Antoine , Kulkarni Amit , Girotto Gustavo Colagiovanni , De La Fouchardiere Christelle , Senellart Helene , Van Laarhoven Hanneke W.M. , Hochhauser Daniel , Mansoor Wasat , Al-Rajabi Raed , Norquist Josephine , Suryawanshi Shailaja , Bhagia Pooja , Metges Jean-Philippe
Published: May 2019

4048

Background: KEYNOTE-181 (NCT02564263) is an open-label, randomized, phase 3 trial in ACC and SCC of the esophagus that evaluated IV pembro 200 mg Q3W for up to 2 years vs investigator choice of single-agent paclitaxel/docetaxel/irinotecan (control). Pembro was superior to control for OS in patients with PD-L1 CPS ≥10 (N = 222; median 9.3 vs 6.7 months; P= 0.0074). Here we present results of prespecified HRQoL analyses in this population. Methods: The EORTC QLQ-C30 and EORTC QLQ-OES18 were administered at baseline; weeks 2, 3, 4, 6, 9, 12, 18; every 9 weeks up to 1 year/end of treatment; and 30-day safety follow-up visit. Data from patients receiving ≥1 dose of study treatment and completing ≥1 HRQoL assessment were analyzed. Least squares mean (LSM) score change from baseline to week 9, 95% CI, and nominal P values were calculated. Time to deterioration (TTD) (≥10-point decline from baseline) was assessed by Kaplan-Meier method and Cox regression model. HRs, 95% CIs, and nominal P values are provided. Results: The HRQoL population included 218 PD-L1 CPS ≥10 patients (107 pembro, 111 control). QLQ-C30 compliance at week 9 was 88.9% for pembro and 83.9% for control. There was no significant difference in LSM between arms (3.68; 95% CI –2.28, 9.64; P= 0.2248) in global health status (GHS)/QoL score. Week 9 QLQ-OES18 compliance was 88.4% for pembro and 83.3% for control. QLQ-OES18 scores were not significantly different between arms. TTD for pain (HR 1.02; 95% CI 0.58, 1.81; P= 0.5282), reflux (HR 1.69; 95% CI 0.83, 3.47; P= 0.9254), and dysphagia (HR 1.81; 95% CI 0.97, 3.37; P= 0.9693) subscales were not significantly different between arms. Conclusions: Over 9 weeks, patients treated with pembro had stable GHS/QoL scores similar to those of patients treated with single-agent docetaxel/paclitaxel/irinotecan. Combined with the superior OS and lower rate of treatment-related AEs seen with pembro, these data support clinically meaningful benefit of pembro in esophageal cancer patients with PD-L1 CPS ≥10. Clinical trial information: NCT02564263.
A pilot study of neoadjuvant FOLFIRINOX followed by chemoradiation for gastric and gastroesophageal cancer: Preliminary results.
Authors: Wo Jennifer Yon-Li , Clark Jeffrey William , Allen Jill N. , Blaszkowsky Lawrence Scott , Keane Florence , Drapek Lorraine C. , Ryan David P. , Corcoran Ryan Bruce , Roeland Eric , Parikh Aparna Raj , Khandekar Melin Janardan , Heist Rebecca Suk , Morse Christopher , Yeap Beow Y. , Ulysse Christine A , Christopher Benjamin , Lanuti Michael , Berger David L. , Mullen John Thomas , Hong Theodore S.
Published: May 2019

4057

Background: We performed a single-arm pilot study of total neoadjuvant approach including FOLFIRINOX and chemoradiation (CRT) with concurrent carboplatin/taxol (C/T) followed by surgery in patients with locally advanced gastric or gastroesophageal junction (GEJ) cancer. Methods: Patients were enrolled on a NCI sponsored, prospective, single arm study (NCT03279237). Key eligibility criteria included: histologically confirmed T3/4 or lymph node (LN) positive gastric or GEJ cancer, ECOG PS ≤1, age 18+, life expectancy > 3 months. Exclusion criteria included: visceral metastases, prior chemotherapy or RT, or prior targeted therapy. Extensive LN disease beyond the surgical field (supraclavicular or para-aortic) was permitted if deemed feasible to be encompassed within a RT field. Laparoscopy was not required. Pts were treated with neoadjuvant FOLFIRINOX x 8, restaging, CRT (45 Gy for gastric, 50.4 Gy for GEJ) with concurrent C/T, restaging, followed by surgical resection. Dose reductions were at discretion of the treating physician. The primary objective was to determine the rate of completion of FOLFIRINOX x 8 followed by CRT delivered in the preoperative setting. Secondary endpoints included: 1) acute toxicity and 2) pathologic complete response (pCR). Results: From Oct 2017 to June 2018, 25 pts were enrolled. Median age was 60 (range:30-76), 17 pts were male (68%). All pts started FOLFIRINOX; 23 (92%) pts completed all 8 planned cycles. Two pts did not complete the planned 8 cycles due to metastatic progression. Rates of grade 3+ overall, gastrointestinal, and hematologic toxicities were 28%, 12%, and 28% respectively. Of the entire cohort, 23 (92%) pts started chemoRT and 22 (88%) pts completed chemoRT (1 pt died during CRT due to pulseless electrical activity arrest). All 22 pts (88%) who completed CRT went for surgical exploration, of whom 2 pts were found with intraoperative metastases. Therefore, 20 (80%) pts underwent surgical resection. At time of abstract, 1 pt’s pathology is in process; 7 pts had a pCR (37% in resected cohort, 28% in ITT cohort), all with R0 resection. Conclusions: Total neoadjuvant FOLFIRINOX followed by CRT is feasible with acceptable rates of treatment completion and grade 3+ toxicity. In our small series, the rate of pCR is promising and a follow-up study is currently planned. Clinical trial information: NCT03279237.
Safety and efficacy of durvalumab following multimodality therapy for locally advanced esophageal and GEJ adenocarcinoma: Results from Big Ten Cancer Research Consortium study.
Authors: Mamdani Hirva , Schneider Bryan J. , Abushahin Laith I. , Birdas Thomas J , Kesler Kenneth , Burney Heather , Perkins Susan M. , Jalal Shadia Ibrahim
Published: May 2019

4058

Background: Concurrent chemoradiation (CRT) followed by esophagectomy is a standard of care for locally advanced esophageal (LA-EAC) and GEJ adenocarcinoma. Approximately 50% of patients (pts) experience disease relapse within the 1st yr after treatment(tx) completion. No adjuvant tx has been shown to improve survival in these pts. Immune checkpoint inhibitors have activity in metastatic PD-L1 positive EAC. Preclinical studies have shown upregulation of PD-1/PD-L1 pathway with RT +/- chemotherapy. Methods: We conducted a phase II trial evaluating safety and efficacy of durvalumab (durva), a monoclonal antibody against PD-L1, in pts with LA-EAC and GEJ adenocarcinoma who have viable tumor in surgical specimen after neoadjuvant CRT and R0 resection. Pts received durva 1500mg IV every 4 weeks for up to 1yr. Results: 24 pts were enrolled from 4/2016-1/2018 (median age: 60yrs (range, 43-70). 18 received carbo/paclitaxel and 6 received cis/5-FU concurrently with radiation. Staging at diagnosis: T2N0 (n=3, 12.5%), T2N2 (n=3, 12.5%),T3N0 (n=6, 25%), T3N1 (n=6, 25%), T3N2 (n=4, 17%), T3N3 (n=1, 4%), T3Nx (n=1, 4%).19 pts (79%) had positive lymph nodes (LNs) at the time of surgery following CRT. 12 pts completed 1yr of tx, 12 came off tx before 1yr because of relapse(6), AEs(5), and consent withdrawal (1). Median number of tx cycles was 12.5 (range, 2-13). Most common AEs were fatigue (n=8, 33.3%) and nausea (n=6, 25%). 3pts (12.5%) developed grade 3 irAEs: pneumonitis (1), hepatitis (1), colitis (1). At median follow up of 14.5 mo (range, 1.7-24mo), 17 are disease free (including 5 who came off tx before 1yr). 7pts (29%) have relapsed (3 alive, 4 died). 6/7pts had distant relapse (lung, brain, bone, cervical LNs) and 1 had locoregional relapse. 1-yr RFS and OS were 79.2% and 95.5%, respectively. 2-yr OS was 59.2%. RFS probability at 26 mo was 67.9%. Median survival after relapse was 11.1 mo (range, 0.1-11.3mo). Conclusions: Adjuvant durvalumab following trimodality therapy for LA-EAC and GEJ adenocarcinoma was safe and feasible with improvement in 1-yr RFS to 79.2% compared to historical rate of 50%. OS results are encouraging in this high risk pt population. Clinical trial information: NCT02639065.
Phase I study of fluzoparib, a PARP1 Inhibitor in combination with apatinib and paclitaxel in patients (pts) with advanced gastric and gastroesophageal junction (GEJ) adenocarcinoma.
Authors: Xu Jian-Ming , Liu Rongrui , Ba Yi , Jiang Da , Wang Mingxia , Zheng Yulong , Wei Jia , Bai Yu-Xian , Lin Lizhu , Xiong Jianping , Zhu Xixi , Zhao Chuanhua , Jia Ru , Zhang Yun , Liu Jianzhi , Zhang Gairong , Li Guangze , Wang Quanren
Published: May 2019

4060

Background: Fluzoparib (SHR3162) is an oral, selective PARP1 inhibitor. In our gastric cancer PDX model, fluzoparib + apatinib + paclitaxel demonstrated significant tumor growth inhibition as compared to apatinib alone, and fluzoparib + paclitaxel. In this phase I study, we hypothesized that the combination of fluzoparib+apatinib+paclitaxel should be safe and active in pts with advanced gastric and GEJ cancer. Methods: Dose-escalation phase (P1) explored 4 dose levels of fluzoparib with a 3+3 design to identify a recommended phase II dose (RP2D) for further study. Pts received fluzoparib (20, 30, 40, 60 mg/twice daily)+apatinib (250mg/day)+paclitaxel (60mg/m2, Day1, 8, 15). Dose-expansion phase (P2) was to assess safety and efficacy. Pts received RP2D of fluzoparib+apatinib+paclitaxel until progression or intolerant toxicity. Treatment was repeated every 4 weeks. Pts had to have progressive disease after standard platinum-based regimen treatment. Adverse events (AE), PK, and response per RECIST 1.1 (every 8 wks in pts with measurable disease) were assessed. Results: 39 pts (median age 58) have been treated in P1 and P2, including fluzoparib 20mg (n=4), 30mg (n=27; 6 pts in P1, 21 pts in P2), 40mg (n=6), and 60mg (n=2). The median treatment duration for this study was 2.8 months. No DLTs were reported in 20mg cohort. One DLT occurred in 30 mg cohort (grade 3 [G3] hypophosphatemia), 1 DLTs (1 grade 4 [G4] febrile neutropenia) occurred and 1 G4 neutropenia occurred and recovered in 3 days in 40mg cohort, 2 DLTs (1 G4 neutropenia, 1 G4 febrile neutropenia) in 60mg cohort. Therefore, 40 mg dose was deemed the MTD. There were no treatment-related deaths on study. The most common AEs≥G3 were neutropenia, febrile neutropenia, and hypertension. 1 treatment-related discontinuation was observed. Of 36 evaluable pts, 12 (30.0%) had confirmed partial response and 13 had stable disease (36.1%). Median progression-free survival was 4.9 months. PK analysis will be presented. Conclusions: The RP2D of combination of fluzoparib + apatinib + paclitaxel is well tolerated and has activity in pts with advanced gastric and EGJ cancer who have failed to platinum-based regimen. Clinical trial information: NCT 03026881.
A phase II study of anti–PD-1 antibody camrelizumab plus FOLFOX4 or GEMOX systemic chemotherapy as first-line therapy for advanced hepatocellular carcinoma or biliary tract cancer.
Authors: Qin Shukui , Chen Zhendong , Liu Ying , Xiong Jianping , Ren Zhenggang , Meng Zhiqiang , Gu ShanZhi , Wang Linna , Zou Jianjun
Published: May 2019

4074

Background: Advanced hepatocellular carcinoma (HCC) and biliary tract cancer (BTC) patients (pts) have very limited treatment options. Considering the immunogenic effects of oxaliplatin, combination of camrelizumab with oxaliplatin-based chemotherapy might bring a better clinical benefit. Methods: That was an ongoing single-arm, multicenter phase 2 trial. Advanced HCC or BTC pts naive to systemic treatment were given camrelizumab (3 mg/kg i.v., every 2 weeks) plus typical FOLFOX4 (infusional fluorouracil, leucovorin and oxaliplatin) or GEMOX (gemcitabine and oxaliplatin) regimen. Primary endpoints were confirmed objective response rate (ORR) per RECIST v1.1 and safety per CTC AE 4.03. Results: From Apr 27, 2017 to Oct 31, 2018, 34 Chinese HCC and 47 BTC pts were treated, in which 27 (79.4%) HCC and 17 (36.2%) BTC pts were HBV-infected. In the 34 evaluable HCC pts, confirmed ORR was 26.5% and disease control rate (DCR) was 79.4%. Median time to response (TTR) was 2.0 mo (range 1.5–5.7). Six of the 9 responses were still ongoing, and median duration of response (DoR) was not reached (range 3.3–11.5+ mo). Median progression-free survival (PFS) was 5.5 mo. At data cutoff, 61.7% BTC pts were still receiving study drug. In the 43 evaluable BTC pts, with a median duration of exposure of 2.9 mo, confirmed ORR was 7.0% and DCR was 67.4%. Median TTR was 1.9 mo (range 1.8–2.1). Median DoR was 5.3 mo (range 3.7–7.0). Median PFS was not reached yet. Median estimates for overall survival in both HCC and BTC were also not reached. Grade ≥3 treatment-related adverse events (TRAEs) occurred in 85.3% of HCC and 57.4% of BTC pts, most commonly neutrophil count decreased (HCC: 55.9%; BTC: 29.8%), white blood cell decreased (HCC: 38.2%; BTC: 21.3%), platelet count decreased (HCC: 17.6%; BTC: 12.8%), and anaphylaxis (BTC: 19.1%). Only one BTC pt stopped treatment due to a TRAE (recurrent Grade 2 anemia related to FOLFOX4). Grade ≥3 immune-related AEs occurred only in 5.9% of HCC (lipase increased) and 3.8% of BTC pts (anaphylaxis). Conclusions: Camrelizumab plus FOLFOX4 or GEMOX chemotherapy was tolerable and might offer a new promising choice for advanced HCC and BTC pts. Clinical trial information: NCT03092895.
Comprehensive genomic profiling in FIGHT-202 reveals the landscape of actionable alterations in advanced cholangiocarcinoma.
Authors: Silverman Ian M. , Murugesan Karthikeyan , Lihou Christine F. , Féliz Luis , Frampton Garrett M. , Newton Robert C , Tada Hiroomi , Albacker Lee A. , Burn Timothy C.
Published: May 2019

4080

Background: Genomic studies of cholangiocarcinoma (CCA) have identified actionable alterations in multiple genes including IDH1, IDH2, FGFR2 and BRAF, but no targeted therapies have been approved for this indication. Pemigatinib (formerly INCB054828) is a selective FGFR1-3 inhibitor currently being evaluated in multiple tumor types, including advanced CCA harboring FGFR2 rearrangements. Comprehensive genomic profiling (CGP) was used to identify and enroll advanced CCA patients with FGFR2 rearrangements into FIGHT-202 (NCT02924376). Here we provide an overview of the genomic landscape of advanced CCA and identify actionable alterations. Methods: CGP was performed on tumor samples from 1104 patients with advanced CCA using FoundationOne, a broad-based genomic panel which identifies mutations, rearrangements, and amplifications in 315 cancer genes. Results: The most frequently altered genes in advanced CCA were TP53 (38.1%), CDKN2A/B (28.8%), KRAS (21.9%), ARID1A (15.7%), SMAD4 (11.3%), BAP1 (10.6%), IDH1 (10.5%), PBRM1 (10.0%), FGFR2 (9.4%), ERBB2 (7.6%), PIK3CA (7.0%), MDM2/ FRS2 (5.8%), and BRAF (4.7%). FGFR2: BAP1 was the most significantly co-occurring alteration pair (odds ratio = 8.5; q-value = 1.08 x 10-13, Fisher’s exact test). 42.9% of patients had at least one alteration for which a targeted agent has been either approved or is under investigation. 91 (8.2%) patients had FGFR2 rearrangements, involving 44 unique partner genes, 37 (84.1%) of which were observed only once. The most prevalent FGFR2 rearrangement partner, BICC1, occurred in only 28 (30.7%) FGFR2 rearrangement positive patients. FGFR2 activating point mutations were found in 13 (1.2%) patients. Of 1,091 evaluable patients for microsatellite instability (MSI) or tumor mutational burden (TMB), only 10 (0.9%) were MSI-H and 13 (1.2%) had high TMB (≥ 20 mutations/megabase). None of the MSI-H or TMB-High patients had FGFR2, IDH1 or IDH2 activating alterations. Conclusions: The high frequency (42.9%) of patients with actionable alterations and myriad FGFR2 rearrangement partners strongly support the use of fusion partner-agnostic CGP in advanced CCA.
Frequency of BRCA mutation in biliary tract cancer and its correlation with tumor mutational burden (TMB) and microsatellite instability (MSI).
Authors: Spizzo Gilbert , Puccini Alberto , Xiu Joanne , Goldberg Richard M. , Grothey Axel , Shields Anthony Frank , Arora Sukeshi Patel , Khushman Moh'd M. , Salem Mohamed E. , Battaglin Francesca , El-Deiry Wafik S. , Tokunaga Ryuma , Philip Philip Agop , Hall Michael J. , Marshall John , Kocher Florian , Korn Wolfgang Michael , Lenz Heinz-Josef , Seeber Andreas
Published: May 2019

4085

Background: Biliary tract cancers constitute ~3% of cancers worldwide with incidence increasing, especially for intrahepatic cholangiocarcinoma (IHC). The prognosis of these tumors remains dismal and novel treatment strategies are needed to improve overall survival. BRCA mutations occur in biliary tract cancers but their frequency in distinct sites of biliary tract cancer is unknown. Moreover, no data are available correlating BRCA mutation with immunogenic markers such as TMB, MSI, or PD-L1 expression. Methods: Tumor samples from 1288 primary biliary tract cancers, comprising IHC (n = 746), extrahepatic cholangiocarcinoma (EHC) (n = 189), gallbladder (GBC) (n=353) were profiled at Caris Life Sciences, Phoenix, AZ. Testing included NextGen SEQ (MiSeq on 47 genes, NextSeq on 592 genes) and PD-L1 IHC (SP142). TMB was calculated based on somatic nonsynonymous missense mutations, and MSI was evaluated by NGS of known MSI loci. Results: BRCA mutations were detected in 3.6% (N = 46) of samples ( BRCA1 0.6%, BRCA2 3%), no differences were seen based on the site of the tumor. In GBC and IHC BRCA2 mutations (4.0% and 2.7%) were more frequent than BRCA1 (0.3% and 0.4, p < 0.05) while in EHC, similar frequency was observed ( BRCA1: 2.1%; BRCA2: 2.6%). There was no significant association with gender or age. In BRCA-mutant biliary tract cancer the most frequently mutated genes were TP53 (55.6%), ARID1A (52.2%) and KRAS (26.1%), KMT2D/C (20%, 13%) and CDKN2A(13%). Overall, BRCA mutations were associated with a higher rate of MSI-H (19.5% vs 1.7%, p = 0.001) and higher TMB in both MSI-H and MSS tumors (p<0.05). When investigated separately, BRCA association with elevated TMB was seen in IHC and EHC, but not in GBC. No correlation was seen with PD-L1 expression. TP53, KMT2D/C, RB1, PTEN, KDM6A mutations and FGFR1 amplifications were significantly higher in BRCA mutated tumors (p < 0.05). Conclusions: BRCA mutations are found in a significant subgroup of biliary tract tumors and are associated with an immunogenic tumor profile. These data provide rationale for trials testing PARP inhibitors in combination with immunotherapy and targeted therapies in patients with BRCA-mutant biliary tract cancers that are MSS.
Cell-free junctional DNA fragment from hepatitis B virus integration in HCC for monitoring postresection recurrence and clonality.
Authors: Wang Ya-Chun , Li Chiao-Ling , Ho Ming-Chih , Lin You-Yu , Tzeng Sheng-Tai , Chen Yun-Ju , Pai Hsin-Yung , Yeh Shiou-Hwei , Chen Pei-Jer
Published: May 2019

4090

Background: About one-third of patients suffer tumor recurrence within the first year after surgical resection of HCC. Early recurrence compromised their overall survival. Timing detection of HCC recurrence and its clonality is required to implement therapeutic trials appropriately. This study examined the virus-host chimera DNA (vh-chimera DNA), generated from junctions of HBV integration in HCC chromosome and released into blood, as a potential circulating biomarker for this clinical setting. Methods: We established a capture-next generation sequencing (NGS) platform to identify the HBV integrations in 50 resected HBV-related HCC. For individual HCC, the major clonal HBV integration sites were chosen to design specific primers for droplet digital PCR (ddPCR) to detect and quantify the vh-chimera DNA in plasma samples, collected either just before surgery or two months after surgery. Levels of vh-chimera DNA were then correlated with baseline HCC size or recurrence in one-year follow up. Results: We succeeded in detecting HBV integrations in the HCC from 44 out of 50 HBV-related HCC patients (88%). The copy number of vh-chimera DNA in plasma at surgery from 42 patients correlated with tumor sizes, with the detection limit at 1.5-2 cm. Among the plasma collected 2 months after surgery, 26.2% of samples contained the same HCC signature vh-chimera DNA as baseline plasma, indicating a possible residual tumor. Consistently, 81.8% of them suffered HCC recurrence within one year. The signature vh-DNA in the plasma suggested the majority of recurrences coming from the original HCC clones, whereas 2 from de novo ones. Conclusions: This study supported vh-chimera DNA as a new circulation marker for detecting the existence of most HBV-related HCC. This new biomarker may complement AFP to help detect residual or recurrent HCC and their clonality after curative therapies.
Impact of tumor shrinkage pattern by biweekly triplet gemcitabine/cisplatin/s-1 for biliary tract cancers: Implication for neoadjuvant therapy (KHBO1401-1A study).
Authors: Kobayashi Shogo , Eguchi Hidetoshi , Kanai Masashi , Wada Hiroshi , Sakai Daisuke , Baba Hideo , Seo Satoru , Taketomi Akinobu , Yoshimura Kenichi , Hatano Etsuro , Nagano Hiroaki , Ioka Tatsuya ,   Kansai Hepatobiliary Oncology Group (KHBO)
Published: May 2019

4093

Background: There have not been any new evidenced regimen for biliary tract cancers (BTC) after ABC-02 study, we conducted biweekly triplet gemcitabine/cisplatin/s-1 regimen (GCS) and compared with conventional doublet gemcitabine/cisplatin regimen (GC) as phase III (KHBO1401) study. Biweekly GCS was proved not only to prolong patients’ survival (HR 0.791 (90% C.I. 0.628-0.996), one-sided P = 0.046) but also to achieve high response rate (42% versus 15%, P < 0.001) and good conversion rate (2.5% versus 0.0%), and would be good for neoadjuvant therapy. Herein, we investigated tumor shrinkage pattern to explore possibilities of neoadjuvant therapy. Methods: Totally 246 patients were enrolled in multi-center phase III KHBO1401 study between 2014 and 2016. Tumor shrinkage pattern (best response, timing, response at 100 days (14 weeks, approx. 6 cycles in GCS and 4 cycles in GC), etc.) and survival were investigated in the patients with measurable BTC (n = 183, 74%, 91 in GCS and 92 in GC) as sub-analysis. P < 0.05 was considered statistically significant. Results: Tumor shrinkage pattern could be divided to 4 categories by the response at 100 days after enrollment; category A ( < -30% in size), B (-30% to 0%), C (0% to +20%), and D ( > +20%). GCS arm contained more category A & B (61 (67%) vs. 33 (36%), P < 0.0001). Each category predicted best response and overall survival (p < 0.0001). Timing for maximum tumor response were different among categories, category A achieved maximum tumor shrinkage at 165 +/- 76 days in GCS and 225 +/- 190 days in GC, category B at 139 +/- 78 versus 154 +/- 82 days, and category C and D did not achieve tumor shrinkage. Maximum tumor shrinkage in category A was -53% in GCS versus -65% in GC (P = 0.0892), and 20% patients in GCS underwent tumor regrowth 154 +/- 143 days later. Conclusions: GCS provided faster and more tumor shrinkage with better survival in the comparison of GC, although it had 20% risk of re-growth after 6 cycles.
The prognostic role of soluble transforming growth factor-β related with soluble programmed death-ligand 1 in biliary tract cancer.
Authors: Kim Jin Won , Ha Hyerim , Lee Kyung-Hun , Nam Ah-Rong , Bang Ju-Hee , Jin Mei Hua , Oh Kyoung Seok , Bang Yung-Jue , Oh Do-Youn
Published: May 2019

4094

Background: We previously reported that soluble programmed death-Ligand 1 (sPD-L1) at pre-chemotherapy indicated the prognostic value for overall survival (OS) and the dynamics of sPD-L1 during palliative chemotherapy correlated with disease burden in biliary tract cancer (BTC). Transforming growth factor (TGF) -β attenuates tumor response to PD1/PD-L1 inhibitors. Strategy of dual targeting of PD1/PD-L1 and TGF-β is now under investigation. This study aimed to evaluate the association between soluble TGF-β (sTGF-β) and sPD-L1, dynamics during chemotherapy and its prognostic role in BTC. Methods: Study population consisted of 90 BTC patients treated with first line chemotherapy. Blood samples at pre-and post-chemotherapy and at disease progression (PD) were prospectively collected. Plasma sTGF-β and sPD-L1 levels were measured by using an enzyme-linked immunosorbent assay. Results: The median progression free survival (PFS) and OS of all patients was 6.9 months (m) (95% CI, 5.2-8.6) and 11.5 m (95% CI, 9.4-13.6). The best response was CR in 7 (7.8%), PR in 20 (22.2%), SD in 52 (57.8%), and PD in 11 patients (12.2%). The mean baseline sTGF-β and sPD-L1 were 16.4 ng/ml and 1.3 ng/ml. There was a positive association between sTGF-β and sPD-L1 in terms of baseline levels and changes after chemotherapy (at pre-chemo, Pearson correlation = 0.578, p < 0.001; change after chemotherapy, Pearson correlation = 0.542, p < 0.001). Patients with higher pre-chemotherapy sPD-L1 ( > 1.3 ng/ml) showed worse OS (9.2 vs 16.2 m, p < 0.001). Both sPD-L1 (1.8 vs 1.0 ng/ml, p < 0.001) and sTGF-β (20.5 vs 11.6 ng/ml, p < 0.001) were increased significantly at the time of PD compared with pre-chemotherapy. Regarding changes after chemotherapy, increased sTGF-β after chemotherapy (Δ > 3.2 ng/ml) had worse prognosis (PFS: 5.1 vs 7.3 m, p = 0.024; OS: 9.2 vs 12.3 m, p = 0.028). This prognostic value of change of sTGF-β after chemotherapy was also significant in multivariable analysis with other clinical factors (PFS: HR = 1.78, p = 0.022; OS: HR = 1.86, p = 0.018). Conclusions: In BTC, there is a positive association between sTGF-β and sPD-L1 value in terms of baseline levels and changes after chemotherapy. sTGF-β could be associated with the survival, particularly, increased value after chemotherapy indicates worse prognosis.
Non-invasive detection of acquired resistance to FGFR inhibition in patients with cholangiocarcinoma harboring FGFR2 alterations.
Authors: Varghese Anna M. , Patel Juber Ahamad A , Janjigian Yelena Yuriy , Meng Fanli , Selcuklu S Duygu , Zimel Catherine , Hyman David Michael , Iyer Gopa , Houck-Loomis Brian , Abou-Alfa Ghassan K. , Berger Michael F. , Lowery Maeve Aine
Published: May 2019

4096

Background: FGFR2 alterations are present in 14% of cholangiocarcinomas (CCA) and are promising targets of investigational FGFR-directed therapies. Cell-free DNA profiling has emerged as a non-invasive approach to monitor disease and longitudinally characterize tumor evolution. We describe the use of circulating tumor DNA (ctDNA) among patients (pts) with FGFR2-altered CCA receiving FGFR-targeted therapy in the identification of acquired FGFR2 mutations (mut) at resistance. Methods: Serial blood samples were collected from 8 pts with FGFR-altered CCA for ctDNA isolation and next generation sequencing. Plasma ctDNA collected at baseline and resistance to FGFR-targeted therapy were sequenced using a custom ultra-deep coverage cfDNA panel, MSK-ACCESS, incorporating dual index primers and unique molecular barcodes to enable background error suppression and high-sensitivity mut detection. The assay was enhanced to include all protein-coding exons and relevant introns of FGFR2. In 5/8 pts, genomic profiling of an initial tumor biopsy was performed. Results: 8 pts with FGFR2-altered CCA (7 gene fusions, 1 amplification) were treated with FGFR-targeted therapies. 7/8 pts exhibited stable disease or partial response. 19 total acquired mut in FGFR2 were detected at resistance in 5/8 pts (between 1-9 unique mut identified in each sample). All mut were located in the kinase domain. Conclusions: Acquired mut in FGFR2 are seen in pts who have developed resistance to targeted therapy. CtDNA can be used to identify these mut at the time of acquired resistance. The multitude of FGFR2 mut observed within individual pts suggest heterogeneity and evolutionary convergence of resistance mechanisms. Our results illustrate the utility of ctDNA as a less invasive way to monitor for signs of resistance and to identify other potential targetable alterations. [Table: see text]