scholarly journals 151P CO-STAR: Surgical conversion feasibility trial of sintilimab (PD-1 inhibitor) combined with doublet chemotherapy (Nab-PTX & S-1) and apatinib (anti-angiogenic TKI) for the first-line treatment of stage IV gastric cancer (GC)

2021 ◽  
Vol 32 ◽  
pp. S1445-S1446
Author(s):  
Q. Xue ◽  
B. Wang ◽  
X. Wang ◽  
X. Ding ◽  
Y. Liu ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Stage Iv ◽  
Feasibility Trial ◽  
Line Treatment ◽  
First Line ◽  
Stage Iv Gastric Cancer ◽  
Doublet Chemotherapy ◽  
First Line Treatment

CO-STAR: Surgical conversion feasibility trial of sintilimab (PD-1 inhibitor) combined with Nab-PTX, S-1 and apatinib for the first-line treatment of stage IV gastric cancer (GC).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e16041-e16041
Author(s):  
Qiang Xue ◽  
Baogui Wang ◽  
Xiaona Wang ◽  
Xuewei Ding ◽  
Yong Liu ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Conversion Rate ◽  
Tumor Response ◽  
Stage Iv ◽  
R0 Resection ◽  
Line Treatment ◽  
First Line ◽  
Stage Iv Gastric Cancer ◽  
Peritoneal Spread ◽  
First Line Treatment

e16041 Background: Chemotherapy and PD-1 inhibitor have shown significant clinical benefits in first-line treatment of GC, overall survival was still dismal. The surgical intervention with curative or life prolonging intention was evaluated as feasible for stage IV GC from clinical trials and retrospective cohorts. Our previous study of cytotoxic chemotherapy (S-1 & PTX) in combination with multi-targets anti-angiogenic TKIs illustrated increased response and R0 resection rate. Given the enhanced response from chemo, PD-1 and TKIs regimens, this trial was designed to assess the feasibility of surgical conversion from this combination in stage IV GC. Methods: This is a prospective, single-arm, single-center, phase II trial. Eligible criteria were treatment naïve, histopathologically confirmed stage IV (AJCC8th) and ECOG PS 0-1 GC adenocarcinoma. Pts were given with sintilimab (200mg, iv, d1) combined with Nab-PTX (w/o peritoneal spread: 260 mg/m2, iv, d1; w/ peritoneal spread: 180 mg/m2, iv, d1 and 80 mg/m2, ip, d1), S-1 (60mg, po, bid, d1-14), and apatinib (250mg, po, qd) every 3 wks. Tumor response was assessed every 2-4 cycles by radiologic imaging and MDT was employed to determine surgical feasibility. Safety run-in was employed in the first 3+3 pts by DLTs to determine the tolerability. The primary endpoint was ORR and R0 surgical conversion rate. Results: 42 pts were enrolled up to 2/2021. The median follow-up was 3.5m (range 0.7-11.3). The median age was 56 yrs (range 31-72), male was 47.6%, and PS 1 was 31.0%. The metastatic factors were characterized as No.16 lymph nodes 54.8% (23), liver 23.8% (10), peritoneum 40.5% (17), Krukenberg 2.4% (1), and extensive metastases (≥2 organs) 42.9% (18). No DLT occurred in initial 6 pts. Of 36 evaluable pts, ORR was 61.1% and DCR was 97.2%. Surgical conversion was currently identified in 18 pts with 94.4% (17) R0 resection, and the R0 surgical conversion rate was 47.2% (17/36). Median treatment cycle in converted pts was 4. 22.2% (4/18) pts achieved pathological complete response (TRG 0), and 27.8% (5/18) pts had major response (TRG 0-1). The most common AEs were grade 1-2, and 1 SAE of hemorrhage grade 4 occurred. No increase of anastomotic leakage, hemorrhage, and abdominal infection, and no surgery caused death and complication caused second operation occurred. The median postoperative length of stay was 9.5d (range 6-16). Conclusions: These preliminary results showed favorable tumor response and acceptable tolerability for potential surgical resection. Sintilimab, doublet chemotherapy, and apatinib might offer an opportunity of cure for stage IV gastric cancer. Trial ID: NCT04267549. Clinical trial information: NCT04267549. [Table: see text]

scholarly journals Prognostic benefit of conversion surgery for HER2 positive stage IV gastric cancer; a case series study of eleven patients treated with trastuzumab-based chemotherapy

2020 ◽  
Vol 6 (1) ◽  
Author(s):  
Koichi Hayano ◽  
Hiroki Watanabe ◽  
Takahiro Ryuzaki ◽  
Naoto Sawada ◽  
Gaku Ohira ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Patients ◽  
Stage Iv ◽  
R0 Resection ◽  
Conversion Surgery ◽  
First Line ◽  
Her2 Positive ◽  
Stage Iv Gastric Cancer ◽  
Gastric Cancer Patients ◽  
First Line Treatment

Abstract Background Since the ToGA trial, trastuzumab-based chemotherapy is the standard treatment for HER2 positive stage IV gastric cancer. However, it is not yet clear whether surgical resection after trastuzumab-based chemotherapy (conversion surgery) can improve survival of HER2 positive stage IV gastric cancer. The purpose of this study is to evaluate the prognostic benefit of conversion surgery in HER2 positive stage IV gastric cancer patients. Case presentation We retrospectively investigated the medical records of the patients with HER2 positive (IHC3(+) or IHC2(+)/FISH(+)) stage IV gastric cancer treated with trastuzumab-based chemotherapy as the first line treatment. Overall survival (OS) was compared between patients with conversion surgery and without. Eleven HER2 positive stage IV gastric cancer patients treated with trastuzumab-based chemotherapy as the first line treatment were evaluated. Response rate was 63.6%, and 6 of 11 patients could receive conversion surgery. R0 resection was achieved in four patients. In Kaplan–Meier analysis, patients who received conversion surgery showed significantly better OS than those without surgery (3-year survival rate, 66.7% vs. 20%, P = 0.03). The median OS of patients who achieved R0 resection is 51.8 months. Conclusions Conversion surgery might have a survival benefit for HER2 positive stage IV gastric cancer patients. If curative surgery is technically possible, conversion surgery could be a treatment option for HER2 positive stage IV gastric cancer.

scholarly journals Results of the use of trastuzumab combined with different chemotherapy regimens in first-line treatment of HER2-positive disseminated gastric cancer

2019 ◽  
pp. 120-127
Author(s):  
N. S. Besova ◽  
T. A. Titova ◽  
S. G. Bagrova ◽  
E. S. Obarevich ◽  
V. A. Gorbunova ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Objective Response ◽  
Stage Iv ◽  
Tumour Regression ◽  
First Line ◽  
Her2 Positive ◽  
Mortality Pattern ◽  
Stage Iv Gastric Cancer ◽  
Triplet Chemotherapy ◽  
Doublet Chemotherapy

Gastric cancer (GC) is one of the most common types of malignant tumour worldwide and is ranked fifth in the cancer incidence pattern and third in the cancer mortality pattern. In the Russian Federation, 39.9% of patients are diagnosed with stage IV gastric cancer, 46.6% of patients die within the first year after diagnosis. The combinations of trastuzumab with platinum derivatives and fluoropyrimidines (trastuzumab + doublet) are regarded as the standard therapy against HER2 positive disseminated gastric cancer. We studied the efficacy and toxicity of the combination of trastuzumab with three-component (triple) chemotherapy regimens (docetaxel or irinotecan + platinum derivatives and fluoropyrimidines). In combination of trastuzumab with triplet chemotherapy, an objective response was achieved in 76.7% of cases, with doublet chemotherapy it was achieved in 60% (p = 0.228), of which complete tumour regression was observed in 10%, control of the disease was reported in 96.7% and 95.0 % (p = 1.0) patients, respectively. The median progression-free survival in patients, who received trastuzumab in combination with triplet chemotherapy, was 9.66 months, in combination with doublet chemotherapy was 11.07 months, the difference was not statistically significant (p = 0.800; OR = 0.908; 95% CI: 0.430–1.918). Median survival of patients is not achieved. The obtained results showed that adding a third cytostatic agent to the standard duplet chemotherapy in combination with trastuzumab does not lead to improvement in the treatment outcomes of first-line therapy in patients with HER2-positive disseminated gastric cancer.

266 Tumour mutation burden (TMB) and efficacy outcomes in the phase III DANUBE study of advanced urothelial carcinoma (UC)

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A292-A292
Author(s):  
Sophie Wildsmith ◽  
Jill Walker ◽  
Anne L’Hernault ◽  
Weimin Li ◽  
Hannah Bye ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Stage Iv ◽  
Small Cell ◽  
Phase Iii ◽  
Survival Outcomes ◽  
Line Treatment ◽  
Small Cell Lung ◽  
First Line ◽  
Unresectable Stage ◽  
First Line Treatment

BackgroundThe phase III DANUBE study assessed the efficacy of the PD-L1 inhibitor durvalumab (D), alone or in combination with the CTLA-4 inhibitor tremelimumab (T), versus standard of care chemotherapy (SoC) for the first-line treatment of unresectable, locally advanced or metastatic UC. The study did not meet its co-primary endpoints of improving overall survival (OS) for D monotherapy vs SoC in patients with high tumor PD-L1 expression or for D+T vs SoC in the intention-to-treat population.1 TMB measurement in blood (bTMB) or tumour (tTMB) has been linked to improved efficacy with PD-1/PD-L1 inhibitors in UC and with D+T in non-small cell lung cancer,2 thus providing a rationale to explore TMB in the DANUBE trial.MethodsBaseline plasma samples from DANUBE were assessed for bTMB using the Guardant OMNI platform, while baseline tTMB was measured in formalin-fixed paraffin-embedded (FFPE) tumour samples using the FoundationOne CDx gene panel. Associations between progression-free survival (PFS) and median and landmark OS with bTMB and tTMB levels at various cutoffs were assessed as part of a pre-specified exploratory analysis. The data cutoff occurred on January 27, 2020.ResultsAmong 1032 patients randomised in DANUBE, 536 (51.9%) were evaluable for bTMB and 623 (60.4%) were evaluable for tTMB. For D vs SoC, bTMB and tTMB were not associated with OS or PFS at any cutoff. For D+T, stronger associations between bTMB and OS as well as PFS were observed with increasing bTMB cutoffs (table 1). At the bTMB cutoff ≥ 24 mut/Mb, 12-month OS rates were 76.7% for D+T and 54.3% for SoC, whereas for bTMB < 24 mut/Mb, 12-month OS rates were 53.4% for D+T and 51.2% for SoC. Similar trends for both OS and PFS were observed with tTMB (table 1).Abstract 266 Table 1Association between TMB and survival outcomes with D+TAssociation between TMB and survival outcomes with D+TConclusionsBoth bTMB and tTMB are potentially useful biomarkers for enriching responses to D+T in previously untreated, advanced UC. Neither bTMB nor tTMB was associated with better outcomes for D monotherapy. Cutoffs of 24 mut/Mb for bTMB and 10 mut/Mb for tTMB appear optimal for D+T in the setting of previously untreated, advanced UC.Trial RegistrationThe trial is registered with ClinicalTrials.gov, NCT02516241, and the EU Clinical Trials Register, EudraCT number 2015-001633-24.ReferencesAstraZeneca. Update on phase III DANUBE trial for IMFINZI and tremelimumab in unresectable, stage IV bladder cancer [press release] March 6, 2020. [https://www.astrazeneca.com/media-centre/press-releases/2020/update-on-phase-iii-danube-trial-for-imfinzi-and-tremelimumab-in-unresectable-stage-iv-bladder-cancer-06032020.html]Rizvi NA, Cho BC, Reinmuth N, et al. Durvalumab with or without tremelimumab vs standard chemotherapy in first-line treatment of metastatic non-small cell lung cancer: The MYSTIC phase 3 randomized clinical trial. JAMA Oncol. 2020:6:661–674.Ethics ApprovalThe study protocol was approved by the Ethics Board at each investigator’s institution.

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