bluuebunny/crossref_metadata_2025 huggingface dataset:
Surgeon and hospital variation in adjuvant chemotherapy delivery to patients with stage III colon cancer.
Authors: Xu Zhaomin , Justiniano Carla Francesca , Becerra Adan Z , Aquina Christopher Thomas , Boscoe Francis P. , Schymura Maria J. , Temple Larissa K. F. , Fleming Fergal J.
Published: September 2018

3596

Background: It is well established that age and comorbidities have significant impact on adjuvant chemotherapy delivery to stage III colon cancer patients. This study examines differences in the hospital and surgeon-specific probabilities of adjuvant therapy delivery to stage III colon cancer patients by comorbidity burden and age. Methods: Patients who underwent surgery for stage III colon cancer from 2004-2013 were included from the New York State Cancer Registry and the Statewide Planning and Research Cooperative System. Comorbidity burden was defined with the Charlson Comorbidity Index (CCI). Multilevel logistic regressions characterized variation in adjuvant chemotherapy delivery among individual hospitals and surgeons by CCI and age. Results: 11575 patients met inclusion criteria, of which 59% received adjuvant therapy. Younger age, lower CCI, and high volume surgeons/hospitals were associated with delivery of adjuvant therapy (p < 0.01). Median time to chemotherapy was 43 days among CCI = 0 vs 48 among CCI≥2. The risk adjusted hospital and surgeon-specific probabilities of adjuvant delivery decreased with increasing CCI and age. The proportion of variation attributable to surgeons, vs hospitals, increased with CCI and age. Hospital variation between the highest and lowest hospitals increased from a 6-fold difference among CCI = 0 to an 11 fold difference among CCI≥2. Surgeon variation increased from a 14-fold difference among CCI = 0 to a 40 fold difference among CCI≥2. Conclusions: Variation in adjuvant chemotherapy delivery to stage III colon cancer patients increased with higher comorbidity burden and age. While a larger proportion of variation is attributable to surgeons among patients with the highest CCI and the most elderly, the vast majority of the variation is related to hospital factors. Even taking into account that some patients may be unfit for adjuvant therapy, this variation in treatment is alarmingly high. [Table: see text]
Microbiota as a new indicator of colorectal cancer (CRC) heterogeneity.
Authors: Sobhani Iradj , Ghozelane Amine , Bergsten Emma Bergsten , Kennedy Sean
Published: September 2018

3615

Background: Location and somatic gene signature of CRCs may impact prognosis and therapy response. The aim was to characterize colon Microbiota in CRC patients regarding location, gene markers and outcome. Methods: Patients (N = 173) signed consent for whole metagenome (shot gun sequencing on Illumina HiSeq2500) analysis of stool DNA: 72 CRC (53 sporadic-S, 19 Lynch-L), 87 asymptomatic subjects (normal colonoscopy), 14 first degree healthy relatives from Lynch families. "MOCAT" pipeline was used, library sorted (Phred quality score ¡20 Alientrimmer v0.4.0) after exclusion of < 35 nt, human genes or phage sequences. Quality sequences were aligned (REFMG.V13) and most abundant genes constructed (MBMA program v0.1). The Shaman program (shaman.c3bi.pasteur.fr) was used. The number of bacteria was estimated (REFMG program). The linear model (GLM) was implemented in the DESeq2 R kit. Dfferences between Control (N = 87) and CRCs (N = 69), between L (N = 19) and S CRCs(N = 50), and between LCRC (N = 19) and Healthy Lynch relatives were obtained after interaction of age, BMI and gender was considered (GLM model). The P < 0.1 value was retained after correction (Benjamini and Hochberg). The specific taxonomic composition of the control and CRC groups was subjected to random analysis ( Caret's R package) with two optimization parameters (precision and kappa) in the model. Results: There was no difference for gender, age (p = 0.08) and BMI (p = 0.187) in the L and S CRCs. Significant differences were observed between Normal and CRCs, C-CRC and L-CRC, L-CRC and first degree relatives based on the common component (similarity of sequences): 13 species differentiated Normal and CCRs, two were more prevalent in L-CRCs. The panels of bacteria linked with location, MSI, Ras mutations, methylation phenotypes and survival were identified. No significant link was observed with TNM Staging: I (N = 17, 2L and 15S), II (N = 12, 5L and 7S), III (N = 20, 10L, 10S), IV (N = 22.1L, 21S). DFS might be dysbiosis dependent. Conclusions: CRC dysbiosis is location-dependent. Several bacteria are associated with Ras mutation, MSI, and methylation status. They may directly or through therapies impact the prognosis. Microbiota signature should be taken in consideration in trials.
KEYNOTE-059 cohort 1: Efficacy and safety of pembrolizumab (pembro) monotherapy in patients with previously treated advanced gastric cancer.
Authors: Fuchs Charles S. , Doi Toshihiko , Jang Raymond Woo-Jun , Muro Kei , Satoh Taroh , Machado Manuela , Sun Weijing , Jalal Shadia Ibrahim , Shah Manish A. , Metges Jean-Philippe , Garrido Marcelo , Golan Talia , Mandala Mario , Wainberg Zev A. , Catenacci Daniel V.T. , Bang Yung-Jue , Wang Jiangdian , Koshiji Minori , Dalal Rita P. , Yoon Harry H.
Published: September 2018

4003

Background: Pembro has shown promising antitumor activity and manageable safety in a phase 1 study of pts with previously treated advanced gastric cancer. We conducted a global, multicohort, phase 2 study of pembro in pts with advanced gastric or gastroesophageal junction (G/GEJ) cancer (KEYNOTE-059;NCT02335411). Methods: Cohort 1 enrolled 259 pts, aged ≥18 y with measurable recurrent or metastatic G/GEJ adenocarcinoma who had progressed on ≥2 prior chemotherapy regimens and had ECOG PS 0-1. Pts received pembro 200 mg Q3W up to 2 y or up to disease progression, investigator/pt decision to withdrawal, or unacceptable toxicity. PD-L1+pts had expression in ≥1% tumor or stromal cells using IHC (22C3 antibody). Primary end points: ORR (RECIST 1.1, by central review), safety, and tolerability. Results: Of 259 pts in cohort 1, 76.4% were men; median age was 62.0 y. 51.7% and 48.3% received pembro as 3rd-line (3L) and 4L+ therapy, respectively. 57.1% had PD-L1+ tumors. At data cutoff (Oct 19, 2016), median duration of follow-up was 5.4 mo (range, 0.5 to 18.7). Overall ORR (CR + PR) was 11.2% (95% CI, 7.6-15.7); 1.9% of pts (95% CI, 0.6-4.4) had CR, 9.3% had PR (95% CI, 6.0-13.5), 17% (95% CI, 12.6-22.1) had SD, and 55.6% (95% CI, 49.3-61.7) had PD. Median DOR was 8.1 mo (range, 1.4+ to 15.1+). ORR was 14.9% (95% CI, 9.4-22.1) in 3L pts and 7.2% (95% CI, 3.3-13.2) in 4L+. In PD-L1+ pts, ORR was 15.5% (95% CI, 10.1-22.4) with 2.0% (95% CI, 0.4-5.8) CR and 13.5% (95% CI, 8.5-20.1) PR; in PD-L1– pts, ORR was 5.5% (95% CI, 2.0-11.6), with 1.8% (95% CI, 0.2-6.5) CR and 3.7% (95% CI, 1.0-9.1) PR. In 3L pts with PD-L1+ tumors, ORR was 21.3% (95% CI, 12.7-32.3), with 4.0% (95% CI, 0.8-11.2) CR; in 3L pts with PD-L1– tumors, ORR was 6.9% (95% CI, 1.9-16.7), with 3.4% (95% CI, 0.4-11.9) CR. Grade 3-5 treatment-related AEs (TRAEs) occurred in 43 pts (16.6%). TRAEs led to discontinuation in 2 pts (abnormal LFT, bile duct stenosis) and were fatal in 2 pts (acute kidney injury, pleural effusion). Conclusions: Pembro showed encouraging efficacy and manageable safety after ≥2 prior lines of therapy in pts with advanced G/GEJ cancer in this large phase 2 trial. Survival and additional biomarker data, including MSI status, will be presented. Clinical trial information: NCT02335411.
Results of the randomized phase II portion of NRG Oncology/RTOG 0848 evaluating the addition of erlotinib to adjuvant gemcitabine for patients with resected pancreatic head adenocarcinoma.
Authors: Safran Howard , Winter Kathryn A , Abrams Ross A. , Regine William , Goodman Karyn A. , Berger Adam C. , Gillin Michael , Philip Philip Agop , Lowy Andrew M. , Wu Abraham Jing-Ching , DiPetrillo Thomas A. , Corn Benjamin W. , Seaward Samantha A. , Haddock Michael G. , Song Suisui , Jiang Yixing , Fisher Barbara Jean , Katz Alan W. , Mehta Sharmila P. , Crane Christopher H
Published: September 2018

4007

Background: NRG/RTOG 0848 is a 2-step study designed to determine whether erlotinib (E) added to gemcitabine (G) (randomized Ph II) &/or adjuvant radiation with concurrent 5-FU or capecitabine following 6 months of systemic chemotherapy (Ph III), improve survival in patients (pts) with resected pancreatic head adenocarcinoma. The erlotinib results are reported here. Methods: Eligible pts include those with resected pancreatic head adenocarcinoma, pathologic stage T1-T3, N0-1, M0; PS 0-1, & CA19-9 ≤ 180 IU/L. Pts in Arms 1 & 2 received G 1 gm/m2 weekly for 3 weeks in a 28-day cycle for 6 cycles. Pts in Arm 2 also received E 100 mg/day. The primary hypothesis for the E portion was that G+E would increase overall survival (OS) compared to G alone. With a 1-sided alpha of 0.15, 200 OS events provide 80%/90% power to detect a signal for an increase in median OS from 22 to 28.8/30.6 months (mos). OS was estimated by the Kaplan-Meier method & arms compared using the log rank test. The Cox proportional hazards model was used to analyze treatment effect. Results: 336 pts were randomized from 11/17/2009 to 2/28/2014, with 163 pts evaluable for G and 159 for G+E. Median age was 63 years (39-86). Most pts had pathologic T3 disease (78%) & CA19-9 ≤ 90 (93%). There are 32 pts (20%) with grade 4 adverse events (AEs) & 2 pts (1%) with grade 5 AEs on G and 27 (17%) & 3 (2%) on G+E arm, respectively. There are fewer grade ≥ 3 GI AEs on the G arm (22%) as compared to the G+E arm (28%), and 110 (69.2%) & 93 (59.6%) pts received at least 85% of planned G dose for the G & G+E arms, respectively. 58% of E pts received at least 85% of planned E dose. The median follow-up for alive pts is 42.5 mos (min-max: < 1-75). With 203 deaths, median & 3-yr OS (95% CI) are 29.9 mos (21.7-33.4) & 39% (30, 45) for G and 28.1 mos (20.7-30.9) & 39% (31, 47) for G+E; log-rank p = 0.62. The hazard ratio (95% CI) comparing OS of G+E to G is 1.04 (0.79- 1.38). Conclusions: The addition of adjuvant E to G did not provide a signal for increased OS in pts with resected pancreatic head cancer compared to G alone. Accrual to the trial is continuing to answer the Ph III radiation question. Clinical trial information: NCT01013649.
A randomized phase II pilot study prospectively evaluating treatment for patients based on ERCC1 for advanced/ metastatic esophageal, gastric, or gastroesophageal junction cancer: SWOG S1201.
Authors: Iqbal Syma , McDonough Shannon , Lenz Heinz-Josef , Ilson David H. , Burtness Barbara , Nangia Chaitali Singh , Barzi Afsaneh , Schneider Charles , Liu Jijun , Dotan Efrat , Guthrie Katherine A , Hochster Howard S.
Published: September 2018

4009

Background: Platinum based treatment (tx) is standard in HER2 negative patients (pts) with advanced esophagogastric cancer (AEGC). Retrospective data suggest intratumoral ERCC1 levels may determine platinum sensitivity. A randomized phase II study was performed in pts with AEGC to explore whether the efficacy of a platinum 5-FU/LV/Oxaliplatin (FOLFOX) vs. non-platinum containing regimen irinotecan/taxotere (IT) differed according to ERCC1 levels. Methods: 203 untreated pts with AEGC, Her2 -, Zubrod PS 0-1, were randomized to FOLFOX vs. IT, stratified by intratumoral ERCC1 low (<1.7) vs. high (≥1.7). Objectives were to assess PFS and OS in all pts treated with FOLFOX compared with IT, and in those pts with low and high ERCC1 levels and to assess for interactive effects between ERCC1 expression and tx arm. Results: 86% of pts had ERCC1 values <1.7. Thus, evaluation of ERCC1 pts in the high subgroup was not feasible. Tx groups were well matched by age, sex, race, ERCC1 level, and site. A series of K-M plots were used to explore whether tx arm differences in PFS varied based on ERCC1 levels; little evidence of such was noted. Grade ≥ 3 anemia, dehydration, diarrhea and fatigue were greater in pts with IT. Grade ≥ 3 neuropathy and decreased neutrophils were greater in pts with FOLFOX. Conclusions: In all pts, FOLFOX had a statistically superior PFS and RR, when compared with IT. In pts with ERCC1 <1.7 receiving FOLFOX, PFS and RR was statistically superior, with no difference in OS. There was no significant evidence of differential treatment effect on PFS across ERCC1 levels. Clinical trial information: NCT01498289. [Table: see text]
Cisplatin/5-FU (CF) +/- panitumumab (P) for patients (pts) with non-resectable, advanced, or metastatic esophageal squamous cell cancer (ESCC): An open-label, randomized AIO/TTD/BDGO/EORTC phase III trial (POWER).
Authors: Moehler Markus H. , Thuss-Patience Peter C. , Brenner Baruch , Longo Federico , Meiler Johannes , Ettrich Thomas Jens , Hofheinz Ralf , Al-Batran Salah-Eddin , Vogel Arndt , Mueller Lothar , Lutz Manfred P. , Borchert Kersten , Greil Richard , Alsina Maria , Karatas Aysun , Van Cutsem Eric , Keller Ralph , Larcher-Senn Julian , Lorenzen Sylvie ,   AIO/BDGO/TTD/EORTC
Published: September 2018

4011

Background: Most ESCC pts have advanced disease at time of diagnosis. Chemotherapy (CTX) is used to improve quality of life (QoL) and overall survival (OS), but still with limited impact. Prior studies suggested increased efficacy of EGFR antibodies (AB) combined with CF (Lorenzen, Ann Oncol 2009). Methods: This open-label, randomized (1:1), multicenter, multinational phase III included pts with non-resectable, advanced or metastatic ESCC (RECIST1.1), not radiochemotherapy (RCTX) eligible and ECOG 0-1. Previous CTX in metastatic setting, concurrent RCTX and exposure to EGFR-AB were excluded. Pts received CF (C 100 mg/m² d1 + F 1000 mg/m²/d, d1-4) or CFP (9 mg/kg d1) q3 weeks until disease progression. Due to more Gr3-4 SAEs in the first 60 Pts with CFP, C was reduced to 80mg/m²d1 Tumor assessment was performed q9 weeks. Primary objective was OS: superiority of CFP (9 months [mo]) over CF (6 mo) with 300 pts (90% power). Results: Between 6.2012-5.2015, 146/155 pts were randomized. After interim analysis for futility, the trial was stopped. 60(83%) of CFP and 55(79%) of CF pts had any AE, mostly diarrhea, hypokalemia, hypomagnesaemia, rash, and hand-foot syndrome. Main Gr≥3 AEs were low neutrophils 21/ 24% and anemia 13/16 % for CFP vs CF, respectively. Gr 3-4 skin reactions and rash were higher in CFP (10%) vs CF (0%). Overall, 51/72 (71%) of CFP and 36/70 (51%) of CF had SAE. Main SAE were dysphagia, acute kidney injury, diarrhea, fevers and febrile neutropenia in 6/6%, 7/4%, 7/3%, 3/6% and 6/1% for CFP vs CF, respectively. For all CFP vs CF pts, median OS was 9.4 vs. 10.2 mo (hazard ratio (HR) 1.17, 95%CI 0.79-1.75; P=0.43). For 56 pts treated with cisplatin 100mg/m²d1, OS was 9.4 vs. 12.9 mo (HR 1.83, 95 % CI 0.98-3.42; P=0.06). After C was reduced (80mg/m²), OS (85 pts) favored CFP vs CF, with 9.8 vs. 8.3 mo (HR 0.84, 95%CI 0.49-1.43; P=0.51). Median PFS for all CFP vs CF pts, was 5.3 vs. 5.8 mo. (HR 1.21, 95%CI 0.85-1.73; P=0.29) respectively. Conclusions: Addition of Panitumumab to CF provided no additional benefit to chemotherapy alone as first-line treatment of ESCC. Biomarker program is going on for further analyses. Clinical trial information: NCT1627379.
A phase II trial of gemcitabine (G), cisplatin (C), and nab-paclitaxel (N) in advanced biliary tract cancers (aBTCs).
Authors: Shroff Rachna T. , Borad Mitesh J. , Xiao Lianchun , Kaseb Ahmed Omar , Varadhachary Gauri R. , Wolff Robert A. , Raghav Kanwal Pratap Singh , Iwasaki Michiko , Masci Peter , Ramanathan Ramesh K. , Ahn Daniel H. , Bekaii-Saab Tanios S. , Javle Milind M.
Published: September 2018

4018

Background: BTCs are often diagnosed at an advanced stage and have a poor prognosis. The standard therapy for aBTCs is the combination of GC. However, the median overall survival (mOS) is dismal at 11.7 months (mos) with a median progression free survival (mPFS) of 8 mos. Methods: A single arm, phase II study was conducted at MD Anderson and Mayo Clinic Arizona. Patients (pts) with aBTC were treated at initial dose level of G/C/N (in mg/m2) at 1000/25/125 (n = 27) which was reduced to lower doses due to grade 3/4 hematological (heme) toxicity (tox) - G/C/N: 800/25/100 (n = 33). Cycles were q21 days with restaging q3 cycles until progression. PFS was the primary endpoint (endpt). Using a Bayesian hypothesis test-based design, we assumed mPFS of 8 mos under the null hypothesis (H0), 10 mos under the alternative (H1). Secondary endpts included mOS, RECIST v1.1 response rate (RR), safety and CA19-9 response. Results: 60 pts were enrolled with data on 51 available as of the time of this abstract (age: median 60 yrs [range 31-77], ECOG PS 0/1 (17/34), M/F (30/21), intrahepatic cholangiocarcinoma/extrahepatic/gallbladder (32/8/11). Median follow-up was 11.5 mos and median number of treatment (trmt) cycles = 5. Pts at initial dose level had significant grade 3/4 heme tox: neutropenia, febrile neutropenia, anemia, and thrombocytopenia leading to trmt discontinuation in 6/27 pts. After dose reduction to G/C/N (in mg/m2) at 800/25/100, trmt was better tolerated with only 4 pts experiencing grade 4 heme tox. Non-heme tox were grade 3 in 10 pts: nausea/vomiting, diarrhea, thromboembolic event/CVA, hypokalemia, constipation, cystitis, LFT elevations. In the initial 51 pts, mPFS = 11.4 mos (95% CI: 6.1, not reached) and mOS not reached (estimated > 20 mos, 1-year survival rate 66.7%; 95%CI: 65.9-92.2%). 34 pts evaluable for response: disease control rate (PR+CR+SD)-82.3% and RR-32.3%. 3 unresectable cases were operated post trmt with 1 pathologic CR. Conclusions: The combination of GCN was well tolerated at adjusted doses and demonstrates encouraging preliminary efficacy having met its mPFS endpt and a 1-year survival rate higher than historical control. These results merit evaluating GC +/-N in a randomized controlled study. Clinical trial information: NCT02392637.
Clinical impact of microsatellite instability in patients with stage II and III gastric cancer: Results from the CLASSIC trial.
Authors: Choi Yoon Young , Kim Hyunki , Yang Han-Kwang , Kim Woo Ho , Kim Young Woo , Kook Myeong-Cherl , Park Young-Kyu , Kim Hyung-Ho , Lee Hye-Seung , Lee Kyung Hee , Gu Mi Jin , Choi Seung Ho , Hong Soon Won , Kim Jong Won , Noh Sung Hoon , Cheong Jae-Ho
Published: September 2018

4022

Background: The clinical implications of microsatellite instability (MSI) in gastric cancer are unclear. We investigated the usefulness of MSI status as a predictor of prognosis and responsiveness to adjuvant chemotherapy in patients with stage II and III gastric cancer. Methods: Tumor specimens and clinical information were collected from patients enrolled in the CLASSIC trial, a randomized controlled study of capecitabine plus oxaliplatin-based adjuvant chemotherapy. Five mononucleotide markers were used to assess tumor MSI status. Results: Of 592 specimens, 36 (6.1%) were MSI-high (MSI-H), whereas others were MSI-low or microsatellite-stable (MSS). Among 286 patients not treated with adjuvant therapy, those with MSI-H tumors had a better 5-year disease-free survival rate than did those with MSI-low/MSS tumors (hazard ratio adjusted by age, sex, tumor grade, disease stage, tumor location: 0.244 [95% confidence interval, 0.069–0.867]; p = 0.0292). Among 306 patients who received adjuvant chemotherapy, MSI-H status did not correlate with better disease-free survival (adjusted hazard ratio: 0.561 [95% confidence interval, 0.190–1.654]; p = 0.2946). Benefits from adjuvant chemotherapy differed by MSI status; although adjuvant chemotherapy improved disease-free survival among patients with MSI-low/MSS (adjusted hazard ratio: 0.634 [95% confidence interval, 0.485–0.828]; p = 0.0008), no benefit was observed in the MSI-H group (adjusted hazard ratio: 1.877 [95% confidence interval, 0.284–12.390]; p = 0.5130). Conclusions: Among patients with stage II and III gastric cancer, a MSI-H status correlated with a favorable prognosis, and adjuvant chemotherapy benefited those with MSI-L/MSS tumors but not those with MSI-H tumors.
PD-L1 expression and response to neo-adjuvant chemotherapy in esophageal adenocarcinoma.
Authors: Parkes Eileen E. , Blayney Jaine K. , McCarron Eamon , Douglas Rosalie V. , Stevenson Leanne , McManus Damian , McQuaid Stephen , Arthur Ken , James Jacqueline , Salto-Tellez Manuel , Noble Fergus , Underwood Timothy J , O'Neill Robert , Fitzgerald Rebecca C. , Kennedy Richard D. , Turkington Richard C.
Published: September 2018

4023

Background: Programmed Death-1 Receptor (PD-1) and its ligand (PD-L1) downregulate T cell activation and suppress tumor killing. This study investigated the role of PD-L1 and tumor infiltrating lymphocytes (TILs) in response to neo-adjuvant therapy and prognosis in esophageal adenocarcinoma (EAC). Methods: Transcriptional profiling of 273 formalin fixed paraffin embedded pre-treatment endoscopic EAC biopsies was carried out using the Almac Diagnostics Xcel array and the expression levels of PD-L1 probesets corresponding to protein encoding extracted. Response was assessed by tumor regression grade (TRG; score ≤ 2 = response). Immunohistochemistry (IHC) for PD-L1 and CD8 was performed in matched resection specimens from 135 patients. All EAC patients were treated with cisplatin-based neo-adjuvant chemotherapy followed by surgical resection between 2003 and 2014 at four UK centers as part of the OCCAMS consortium. Associations between expression, protein levels and TRG were assessed by Kruskal-Wallis, Mann-Whitney Unpaired, Spearman rank correlation or chi-squared tests. Survival analysis was performed using Cox Proportional Hazards regression. Results: High PD-L1 gene expression in the pre-chemotherapy biopsies was associated with pathological response (TRG ≤ 2; p = 0.02) following neo-adjuvant chemotherapy. PD-L1 ( > 5%) was expressed in the tumor or stromal cells in 4% and 15% of resection specimens respectively. PD-L1 gene and IHC expression ( > 5%) were closely associated between the biopsies and both the tumor (p = 0.032) and stroma (p = 0.019) of the matched resection specimens. Patients with PD-L1 IHC positivity in tumor cells demonstrated improved relapse-free survival (HR 0.314; 95% CI 0.099-0.997; p = 0.049) and positive stromal PD-L1 IHC staining correlated with pathological response (p = 0.05). Biopsy gene expression of PD-L1 and CD8 was closely associated (p = 0.024) and the presence of CD8+ TILs in the microenvironment strongly correlated with tumor (p < 0.001) and stromal (p < 0.001) PD-L1 positivity. Conclusions: High PD-L1 expression in the pre-treatment biopsies in EAC is predictive of response to neo-adjuvant chemotherapy and may aid selection of conventional and immune-targeted agents.
Enteral nutrition to improve nutritional status, treatment tolerance, and outcomes in patients with esophageal cancer undergoing concurrent chemoradiotherapy (CCRT): Results of a prospective, randomized, controlled, multicenter trial (NCT 02399306).
Authors: Li Tao , Lv Jiahua , Zhu Guangying , Li Jie , Zhu Shu chai , Wang Jianhua , Xing Ligang , Yang Daoke , Xie Conghua , Shen Liangfang , Zhao Ren , Shi Hanping , Lang Jinyi
Published: September 2018

4033

Background: Patients with esophageal cancer undergoing CCRT are at high risk of malnutrition. The aim of this study was to investigate the influence of enteral nutrition on nutritional status, treatment tolerance and outcomes in esophageal cancer patients undergoing CCRT. Methods: Patients with inoperable esophageal cancer were randomly assigned (2:1 ratio) to the enteral nutrition group (EN group) or the control group. Patients in the EN group were supported with individual enteral nutrition intervention according to the nutritional status assessment results. The control group was treated with conventional diet guidance. The primary endpoint was the change in body weight from baseline after treatment. Secondary endpoints were nutrition related blood parameter changes, treatment tolerance and outcomes. Results: Between Mar. 2015 and Jan. 2017, 158 patients from ten hospitals were randomised into the EN group (n = 106) and the control group (n = 52). Following CCRT, patients in EN group lost only 0.72±3.27 kg of body weight compared with 2.10±2.89 kg in the control group (P < 0.001). Participants who received EN had less decline than controls in serum albumin (2.66±5.05 g/L and 4.75±4.94 g/L, P < 0.001) and hemoglobin (10.29±15.78 g/L and 18.48±14.66 g/L, P < 0.001). Grade 3/4 leukopenia in the control group was significantly more frequent than the EN group (33.3% vs. 20.0 %, P = 0.011). Patients supported on EN experienced greater chemoradiotherapy completion rates (92.5% vs. 67.3%, P = 0.001) and lower infection rates (18.8% vs 31.7%, P = 0.021). There was significant difference in tumor response between two groups (EN group: 81.1%, control group: 67.3%, P = 0.004). The 1- and 2-year OS rates in the EN group were significantly greater (89.6% and 75.4%, respectively) compared with the control group (78.5% and 57.9%, respectively). Conclusions: Enteral nutrition may be advantageous in patients with esophageal cancer undergoing CCRT by improving nutritional status, treatment tolerance and outcomes. Clinical trial information: NCT 02399306.
A phase II study of early FDG-PET evaluation after one-cycle chemotherapy in patients with locally advanced esophageal squamous cell carcinoma treated with neoadjuvant chemoradiotherapy: Final report.
Authors: Huang Ta-Chen , Lin Chia-Chi , Tzen Kai-Yuan , Wu Yun-Chun , Cheng Jason Chia-Hsien , Lee Jang-Ming , Wang Hsiu-Po , Huang Pei-Ming , Hsu Feng-Ming , Yeh Kun-Huei , Cheng Ann-Lii , Hsu Chih-Hung
Published: September 2018

4042

Background: The optimal use of the metabolic tumor response measured by 18fluorodeoxyglucose positron emission tomography (FDG-PET) in the treatment of esophageal cancer is currently unknown. We launched a phase II clinical trial to evaluate the early metabolic response to one-cycle chemotherapy in locally advanced esophageal squamous cell carcinoma (ESCC) patients, who subsequently received neoadjuvant chemoradiation (neo-CRT) followed by surgery. Methods: ESCC patients with stage T3 or N1M0 or M1a (AJCC, 6th edition) were enrolled to receive one-cycle chemotherapy, day 1 and 8 doses of paclitaxel, cisplatin, and 24-hour infusional 5-fluorouracil and leucovorin, followed by paclitaxel/cisplatin- based 40Gy neo-CRT and surgery. FDG-PET was performed at baseline and day 14 of the one-cycle chemotherapy. The primary endpoint is pathological complete response (pCR) to neo-CRT. We hypothesized that early PET responders, defined as > 35% reduction of maximum standardized uptake value (SUVmax) from the baseline, would significantly improve pCR. Results: Between Feb 2008 and Mar 2012, 66 patients (M: F = 61: 5) were enrolled. Their clinical stages were: II or III, 56; IVA, 10. Forty seven received surgery. The pCR rate per surgical population was 34.0%. The median progression-free survival (PFS) and overall survival (OS) for the whole study group was 16 months (95% CI 9-27) and 22 months (95% CI 16-40), respectively. A total of53 patients were evaluable for PET response. The early PET response was not associated with high pCR rate or better survivals. However, in an exploratory analysis, the post-chemotherapy SUVmax was an independent prognostic factor for pCR, PFS and OS. A predictive model for pCR composed of weight loss and the post-chemotherapy SUVmaxwas established with an AUC of 0.84. Conclusions: Our study failed to validate the predictive value of predefined early PET response to one-cycle chemotherapy for pCR to neo-CRT in locally advanced ESCC patients. However, the FDG-PET SUVmax after one-cycle chemotherapy may have prognostic and predictive significance, and may be explored in further studies. Clinical trial information: NCT01034332.
A multicentre, phase II study with cabazitaxel in previously treated patients with advanced or metastatic adenocarcinoma of the oesophagogastric junction and stomach (CABAGAST).
Authors: Schmalenberg Harald , Pauligk Claudia , Zander Thomas , Reichart Alexander , Lindig Udo , Kleiss Mathias , Müller Lothar , Bolling Claus , Seufferlein Thomas , Reichardt Peter , Kullmann Frank , Eschenburg Henning , Schmittel Alexander , Egger Matthias , Block Andreas , Al-Batran Salah-Eddin , Goetze Thorsten Oliver
Published: September 2018

4054

Background: This is a single-arm study to determine prolonged ( > = 4 months) disease control rate with cabazitaxel administered in second- (or later) setting for patients with advanced or metastatic adenocarcinoma of the esophagogastric junction (EGJ) and stomach. Methods: 65 patients with advanced EGJ and stomach cancer were treated with 20mg/m2 Cabazitaxel every 3 weeks for a maximum of 6 cycles. Main objective of the study was a prolonged Disease Control Rate (pDCR: CR, PR or SD lasting at least 4 months). Secondary Outcome Measures were overall survival (OS), progression-free survival (PFS), response rate by subgroup (with vs without previous treatment with a taxane) and toxicity. Patients were assessed for tumor response every 6 weeks during therapy and during follow-up (up to 12 months). Results: 65 patients (median age: 63, range 31-86 years) were assigned. Median no. of prior therapies was 2. 80% had received prior taxane therapy. Patients received a median of 2 cycles of cabazitaxel. Efficacy results are shown for the per protocol (PP) population. pDCR rate was 12.7%, (95%CI: 5,3%- 24.5%). pDCR was 20.0% in 2nd line patients (95%CI: 6.8%-40.7%) and 30.0% (95%CI: 6.7%-65.2%) in all lines in patients without prior taxane use. Response Rate was 5.5% (95%CI: 1.1%-15.1%) in total PP and 20.0% in the population without prior taxane use. Median OS was 4.6 months (7.4 months without prior taxane vs 3.8 months with prior taxane). Median PFS was 1.38 months (95%CI: 1.28- 1.87) with and 2.01 months (95%CI: 0.20- 4.67) without prior taxane use. Most common grade 3/4 toxicities were neutropenia in 13% of the patients, pain (12%), leucopenia (10%), anemia (10%), fatigue (10%) and nausea (10%). Conclusions: Cabazitaxel is active in heavily pretreated patients with metastatic and advanced esophagogastric junction and gastric adenocarcinoma. Toxicity is moderate. Patients without prior taxane use derived more benefit from Cabazitaxel. Clinical trial information: NCT01956149.
The Nationwide Cancer Genome Screening Project in Japan, SCRUM-Japan GI-screen: Efficient identification of cancer genome alterations in advanced esophageal cancer.
Authors: Nakashima Yuichiro , Kojima Takashi , Hara Hiroki , Kato Ken , Kajiwara Takeshi , Hironaka Shuichi , Nakatsumi Hiroshi , Kato Takeshi , Moriwaki Toshikazu , Naruge Daisuke , Esaki Taito , Izawa Naoki , Kadowaki Shigenori , Tamura Takao , Miki Izumi , Sudo Tomohisa , Nomura Shogo , Shitara Kohei , Ohtsu Atsushi , Yoshino Takayuki
Published: September 2018

4062

Background: We have conducted the Nationwide Cancer Genome Screening Project in Japan since April 2015 using Next Generation Sequencing in advanced non-colorectal gastrointestinal (GI) cancer (aNon-CRC), called as the SCRUM-Japan GI-SCREEN. The objective is to evaluate the frequency of cancer genome alterations in aNon-CRC and to identify patients who are candidate for clinical trial for corresponding targeting agents. Methods: This study is ongoing with the participation of 20 major cancer centers. Patients with aNon-CRC, including advanced esophageal cancer (aEC), who plan to or receive chemotherapy were eligible. DNA and RNA were extracted from FFPE tumor samples and were analyzed by the Oncomine Cancer Research Panel (OCP) which allows to detect gene mutation, copy number variant (CNV) and fusions across 143 genes in a CLIA certified CAP accredited laboratory. The detected genomic variant data were classified according to genetic drivers of cancer including gain- and loss-of-function or single nucleotide variant based on the Oncomine Knowledgebase. In this presentation, we show the results of aEC cohort. Results: As of October 31st in 2016, a total of 180 aEC samples were analyzed. The sequence with the OCP was successfully performed in 121 (67.2%). Out of 157 patients except for the 23 patients in which precise data is not collected, the proportion of sample and histology type is followed; surgical specimen 58.0%, squamous cell carcinoma 92.4%. The frequently detected mutations in 114 samples of which results were available were TP53 (77.2%), NFE2L2 (23.7%), CDKN2A (9.6%), PIK3CA (7.0%), RB1 (6.1%), and CNVs were CCND1 (37.7%), EGFR (7.9%), MYC (7.9%), SOX2 (6.1%), ATP11B (5.3%), NKX2-1 (5.3%). ERBB2 amplification was identified in 3 cases (2.6%) and FGFR3-TACC3fusion was identified in one case (0.9%). Conclusions: This nationwide screening system is efficient to detect rare gene alterations in aEC. This novel knowledge provides an intriguing background to investigate new target approaches and represents a progress toward more precision medicine. Clinical trial information: UMIN000016344.
A phase 2 trial of regorafenib as a single agent in patients with chemotherapy refractory advanced and metastatic biliary adenocarcinoma/cholangiocarcinoma.
Authors: Sun Weijing , Normolle Daniel Paul , Bahary Nathan , Ohr James , Lembersky Barry C. , Patel Krishna , Patel Anuj K. , Lee James J. , Chu Edward , Streeter Natalie , Drummond Summer , Morcos John P. , Sulecki Matthew Gerard , Geller David A. , Marsh J. Wallis , Tsung Allan , Zeh Herbert
Published: September 2018

4081

Background: Biliary adenocarcinoma/cholangiocarcinoma is a rare but aggressive neoplasm. Most patients present with unresectable or metastatic disease with 5-year survival rate ~5%. No second-line regimen has demonstrated clinical benefit in this disease. Regorafenib is an oral multi-kinase inhibitor with potent antitumor activity. This single arm phase II study evaluates the efficacy and safety of regorafenib as a single agent in advanced or metastatic biliary carcinoma/cholangiocarcinoma pts who failed systemic chemotherapy. Methods: Patients with ECOG PS 0-1and adequate liver, kidney and bone marrow function were given regorafenib orally once daily, 21 days on and 7 days off in a 28-day cycle. The initial dose of 160 mg was given to the first 3 patients. After toxicity assessment, the dose was reduced to 120 mg for the subsequent pts. The primary endpoint is PFS with the null hypotheses of 2.0 months, and median PFS ≥3.5 months as evidence of the study drug activity (α = 0.10, 80% power). Secondary objectives include OS, RR, and DCR. Results: Thirty-seven patients received at least one dose of regorafenib, of whom 28 were evaluable for efficacy. All had previous gemcitabine/cisplatin treatment. The mean age was 62.5 (34.5-82.8) with 17 (46%) females. PR was achieved in 3 (10.7%), SD in 18 (64.3%, with DCR of 75%), and PD in 7 (25%). For all 37 patients, median PFS was 3.55 months (95% CI = 2.1- 5.72) and mOS was 5.55 months (95% CI = 4.04 -NA) with survival rate of 42 % at 12 months, and 38% at 18 months. Medan PFS and OS of 30 patients who had ≥1 cycle were 3.91 months (95% CI = 3.55-9.79) and 13.4 months (95% CI = 5.06 - NA), respectively. The overall toxicity profile was as expected, with G3/4 AE’s of 40.5%. The most common toxicities were HTN, hypophosphatemia, hand-foot skin reaction, and increased serum bilirubin. Dose modification was required in 11 (30.6%) patients. Tumor samples were collected in 80% of patients, with planned correlative studies underway. Conclusions: This study showed promising efficacy of regorafenib in chemotherapy refractory advanced/metastatic cholangiocarcinoma. Further studies to confirm the clinic efficacy are recommended. Clinical trial information: NCT02053376.
Effect of sorafenib (S) starting dose and dose intensity on survival in patients with hepatocellular carcinoma (HCC): Results from a Canadian multicenter HCC database.
Authors: Alghamdi Mohammed Abdullah , Lee-Ying Richard , Sim Hao-Wen , Samawi Haider , Knox Jennifer J. , Romagnino Adriana , Ko Yoo-Joung , Chan Kelvin K. , Swiha Mina , Batuyong Eugene , Cheung Winson Y. , Tam Vincent C. ,   On Behalf of the CHORD Consortium
Published: September 2018

4084

Background: The SHARP trial showed that S improves survival in advanced HCC. Full dose (FD) S at 400mg bid can be difficult to tolerate, so some clinicians begin with a reduced dose (RD) & escalate as tolerated to maximum dose. The purpose of this study was to determine whether starting dose or dose intensity of S affects survival. Methods: All patients treated with S for HCC from 01/2008 to 06/2016 in British Columbia, Alberta, Ontario (Princess Margaret Cancer Centre & Sunnybrook Odette Cancer Centre), were included. Patient demographics, clinical, tumor characteristics, S starting dose & mean dose intensity were collected & analyzed. Patients were dichotomized into starting FD or RD of S. Mean dose intensity was categorized into > 75%, 50-75% & < 50%. Survival outcomes were assessed with Kaplan-Meier curves & compared with the log-rank test. A Cox-proportional hazard model was constructed with starting dose, dose intensity & relevant clinical & pathologic factors to assess their impact on survival. Results: We included 681 patients. Median age 64 years, 80% men, 37% East Asian, & most frequent causes of liver disease were hepatitis B (33%) & C (29%). ECOG performance status prior to starting S was 0 in 30% & 1 in 60%. Most patients were Childs-Pugh A (86%) at start of S. Overall median survival was 9.1 months (m). S was started at FD in 42% of patients & 31% had a dose intensity > 75%. The median survival for starting FD & RD was 9.4 m & 8.9 m, respectively (p = 0.15). The median survival for a dose intensity > 75% was 9.5 m, 50-75% was 12.9 m & < 50% was 7.1 m (p = 0.005). In multivariate models that adjusted for demographic, stage, performance status, AFP, prior treatment, toxicity & liver function, starting dose (HR 1.1, 95%CI 0.86-1.3, p = 0.51) & dose intensity (50-75% HR 0.93, 95% CI 0.73-1.2; < 50% HR 0.89, 95% CI 0.69-1.1, p = 0.65) were not predictors of survival. Conclusions: Based on our multi-center database, starting HCC patients on a RD of S may be a reasonable since it does not appear to compromise survival. Patients receiving a dose intensity of S at 50-75% appear to have a superior median survival, though this is not significant after controlling for baseline characteristics.
A prospective analysis of germline alterations (GA) in biliary tract cancer (BTC).
Authors: Lowery Maeve Aine , Jordan Emmet , Kemel Yelena , Mukherjee Semanti , Cercek Andrea , Kemeny Nancy E. , Varghese Anna M. , Rusek Matthew , Boucher Taryn Mary , Mandelker Diana , Berger Michael F. , Ptashkin Ryan , Hyman David Michael , Klimstra David , Saltz Leonard , O'Reilly Eileen Mary , Robson Mark E. , Stadler Zsofia Kinga , Offit Kenneth , Abou-Alfa Ghassan K.
Published: September 2018

4085

Background: The incidence of hereditary cancer predisposition syndromes in patients (pts) with BTC is unknown. Cholangiocarcinoma has been reported in pts with germline mutations in BAP1, BRCA1/2, and mismatch repair genes. These associations are poorly characterized to date and the majority of pts do not undergo clinical germline analysis (CGA). Methods: Pts with BTC were offered consent to CGA between 01/2016 and 01/2017 under an IRB approved protocol (NCT01775072). Using the MSK-IMPACT platform, 76 genes associated with hereditary cancer predisposition were analyzed for germline variants and matched tumor samples were analysed for somatic alterations in > 340 genes. Demographic and clinical data were collected. Results: 78 patients were accrued: Intrahepatic = 52, extrahepatic = 13, gallbladder = 13. Median age at diagnosis was 57 years (range 21-80), 45 (58%) had a positive family history of cancer in at least one 1st degree or two 2nd degree relatives. 7 patients had a personal history of cancer. A pathogenic or likely pathogenic GA was identified in 16 pts (20%). (See table). Conclusions: Prospective analysis of GAs in pts with BTC, unselected by family history or age, revealed potentially actionable findings in 20% of pts. CGA in pts with BTC may benefit patients and their families in view of screening and therapeutic implications. [Table: see text]
Blood measurements of neuroendocrine tumor (NET) transcripts and gene cluster analysis to predict efficacy of peptide radioreceptor therapy.
Authors: Bodei Lisa , Kidd Mark S. , van der Zwan Wouter A , Drozdov Ignat , Baum Richard P. , Kwekkeboom Dik J. , Krenning Eric , Modlin Irvin Mark
Published: September 2018

4091

Background: Peptide receptor radionuclide therapy (PRRT) capitalizes on somatostatin receptor (SSR) overexpression on NETs to deliver targeted isotope therapy. Objective prediction of efficacy remains to be established. Functional imaging of SSR expression (SRE) is used as a predictor of efficacy. Biomarkers e.g. circulating CgA, are ineffective. Circulating NET transcript analysis (NETest) integrated with tumor grade provides a Predictive Quotient Index (PQI) of PRRT. We validated the utility of this PRRT complementary diagnostic in a prospective, blinded study. Methods: 177Lu-PRRT (29.1±2.2 GBq). NETs ( n= 35); with progressive disease (66%). Baseline evaluations: Clinical status, Grade (Ki67), SRE, CgA (NeoLisa, ULN > 108ng/ml), and NETest (qRT-PCR - multianalyte algorithmic analyses, ULN > 14%). PQI: “omic” NETest gene expression (regulating metabolism and growth factor signaling) mathematically combined with Ki67 index. PQI has two prediction outputs: “responder” (R) vs “non-responder” (NR). Disease control was by RECIST criteria (R vs NR). All samples were blinded. Statistics: Cox proportional multiple regression, Kaplan-Meier survival, & McNemar-test. Results: At restaging, the overall response (disease control rate) was 77%; median PFS not reached (follow-up 4-13 months). Histology: GI: 5; GII: 21; GIII 1; and lung: TC: 2; AC: 5. SRE was Grade 3 (80%). Baseline CgA was 1556±1454ng/ml (89% elevated) and NETest was 60±21% (100% elevated) respectively. Predictive accuracies of SRE, clinical status, CgA levels ( > 2ULN) and NETest ranged from 25-54% (not-significant). PQI was the only predictive marker by multivariate analysis ( p= 0.002). The PQI diagnostic was 92% concordant with outcome and significantly more accurate than all other markers (McNemar: p< 0.002). Cox-proportional modeling confirmed PQI utility (OR: 9.1, p< 0.004). K-MS analysis identified significantly different mPFS between R (not reached) and NR (9.3 months; HR: 8.3, p< 0.0005). Conclusions: A pre-PRRT analysis of circulating NET genes, the predictive quotient index comprising “omic” analysis and grading, is validated to predict the efficacy of PRRT therapy in GEP and lung NETs.
Pre-existing symptoms, resource utilization, and healthcare costs prior to diagnosis of neuroendocrine tumors: A SEER-Medicare database study.
Authors: Shen Chan , Chu Yiyi , Dasari A. , Zhou Shouhao , Halperin Daniel M. , Xu Ying , Shih Ya-Chen T. , Yao James C.
Published: September 2018

4092

Background: The incidence and prevalence of neuroendocrine tumors (NETs) are continually increasing. While it is known that NET symptoms often predate diagnosis, the prevalence of these symptoms and the impacts on resource utilization and costs are largely unknown. Methods: We identified 12,052 elderly patients diagnosed with NET between 1/2003 and 12/2011 by ICD-O-3 codes from the Surveillance, Epidemiology and End Results (SEER)-Medicare database with continuous Medicare Parts A and B enrollment during the one year before NET diagnosis. We used propensity score matching to identify a group of comparable elderly patients from a non-cancer Medicare cohort. We captured patients’ potentially relevant conditions (defined as > 1 indicative claim), resource utilization and costs from patients’ medical claims during the year before diagnosis. We examined a) resource utilization in terms of number of outpatient visits, percentage of patients having any emergency room (ER) visits and hospitalizations, and b) health care costs including inpatient, outpatient and total costs. We used chi-square test for categorical variables and Mann-Whitney U test for continuous variables. Results: NET patients were more likely to have diagnoses of diarrhea (8% vs. 2%), abdominal pain (37% vs. 8%), irritable bowel syndrome (1.5% vs. 0.6%), hypertension (72% vs. 55%), heart failure (16% vs. 8%), and peripheral edema (7% vs. 4%) compared to the non-cancer control group. They also had much higher resource utilization including number of outpatient visits (mean: 27.25 vs. 18.45); and percentage with ER visits (64% vs. 36%), and hospitalizations (66% vs. 34%). Similarly, NET patients incurred significantly higher total (mean: $32924 vs. $10048), outpatient (mean: $8869 vs. 4580), and inpatient costs (mean: $24055 vs. $10048). All p < 0.001. Conclusions: To the best of our knowledge, this is the first population-based study to examine potentially relevant pre-existing symptoms, resource utilization and healthcare costs before NET diagnosis. NET patients were more likely to have certain conditions and incurred higher resource utilizations and costs in the year preceding diagnosis of NET.
A phase 2 study of galunisertib (TGF-Β R1 inhibitor) and sorafenib in patients with advanced hepatocellular carcinoma (HCC).
Authors: Kelley Robin Kate , Gane Edward , Assenat Eric , Siebler Jurgen , Galle Peter R. , Merle Philippe , Ollivier-Hourmand Isabelle , Cleverly Ann , Gueorguieva Ivelina , Lahn Michael M. F. , Faivre Sandrine J. , Benhadji Karim A. , Giannelli Gianluigi
Published: September 2018

4097

Background: TGFβ signaling is associated with HCC progression. Inhibition of TGFβ R1 potentiates activity of sorafenib in in-vitro and in-vivo models. Here we report the clinical activity of galunisertib (G) plus sorafenib (S) in pts with incurable HCC and no prior systemic therapy. Methods: Eligibility criteria included incurable HCC with measurable disease per RECIST 1.1, no prior systemic therapy, Child Pugh A, ECOG PS ≤1.G was administered as 80 mg PO BID (lead-in Cohort 1) or 150 mg PO BID (lead-in Cohort 2 and expansion cohort), as intermittent dosing of 14 days on/off (28 days = 1 cycle). S was administered continuously as a 400 mg PO BID. Primary objective was to characterize time-to-progression (TTP) and biomarker changes in pts. Secondary objectives included evaluation of OS, PK, and toxicity (CTCAE v 4.0). Results: 47 pts were enrolled (Cohort 1 = 3, Cohort 2 and expansion cohort = 44). In the 150 mg BID cohort: Male = 88.6%; median age = 64 years; PS = 0/1, 81.8%/18.2%; etiology: hepatitis C = 34.1%, hepatitis B = 18.2%, alcohol = 20.5%, multiple = 13.6%; AFP≥200 µg/L = 50%; portal vein invasion = 34.1%. Incidence of AEs was similar between G dose levels. Overall in the 150mg BID cohort, treatment related AEs ( > 15%) were hand and foot syndrome (61.4%), diarrhea (40.9%), pruritus (22.7%), anemia and weight loss (20.5%), fatigue (29.5%), alopecia (18.2%), myalgia (22.7%), decrease in platelet count and nausea (15.9%). Two pts on 150 mg BID discontinued treatment due to study drug related AEs (anemia and weight loss). PK of G at 150 mg BID (n = 12) when co-administered with S, was similar to that observed in the G monotherapy study. G was rapidly absorbed and had an elimination half-life of approximately 8h. Median TTP (RECIST) was 4.1 (2.8, 5.5) months. OS, with a high censor rate of 55% was not mature at the time of this data cutoff. Median OS was 17.9 (14.8, NE) months. Conclusions: The combination of G plus S demonstrated acceptable safety and a meaningful OS of 17.9 months in an advanced HCC population. TTP was similar to S monotherapy in contemporary clinical trials though interpretation is limited by single arm design. Clinical trial information: NCT01246986.