Clinical Study of Sintilimab as Second-Line or Above Therapy in Patients With Advanced or Metastatic Gastric Cancer: A Retrospective Study

BackgroundThe present study was conducted to analyze the clinical efficacy and safety of sintilimab as second-line or above therapy for patients with advanced or metastatic gastric cancer.MethodsPatients with advanced or metastatic gastric cancer that progressed after prior systemic therapies and treated with sintilimab from March 2019 to July 2020 were retrospectively analyzed in this study. The primary end point was progression-free survival (PFS). Secondary end points included objective response rate (ORR), disease control rate (DCR), overall survival (OS), and safety.ResultsFifty-two patients with advanced or metastatic gastric cancer received sintilimab monotherapy or combination therapy after they failed from prior systemic therapies. Eight patients achieved partial response (PR), 26 patients had stable disease (SD), and 18 patients had progressive disease (PD). The ORR and DCR were 15.4% (8/52) and 65.4% (34/52), respectively. Median PFS was 2.5 months (95% CI = 2.0–3.0), and median OS was 5.8 months (95% CI = 4.9–6.7). The ORR and DCR were 30.0% (6/20) and 80.0% (16/20), respectively, in intestinal subtype, which were superior than in non-intestinal subtype (ORR: 6.3%, DCR: 56.3%). Patients with intestinal subtype obtained longer PFS (4.0 vs. 1.9) and OS (9.0 vs. 4.1) than those with non-intestinal subtype. The incidence of grade 3–4 adverse events was 44.2%.ConclusionsSintilimab monotherapy or combination therapy provides a feasible therapeutic strategy for patients with advanced or metastatic gastric cancer who failed from prior systemic therapies. The efficacy of sintilimab in intestinal subtype was superior than that in non-intestinal subtype.

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Salvage immune checkpoint inhibitor (ICI) plus tyrosine kinase inhibitor (TKI) combination therapy for metastatic renal cell carcinoma (mRCC).

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.e16567 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. e16567-e16567

Author(s):

Anish B. Parikh ◽

Sarah P. Psutka ◽

Yuanquan Yang ◽

Katharine Collier ◽

Abdul Miah ◽

...

Keyword(s):

Combination Therapy ◽

Immune Checkpoint Inhibitor ◽

Kinase Inhibitor ◽

Objective Response ◽

Progression Free Survival ◽

Standard Of Care ◽

Free Survival ◽

Kaplan Meier ◽

Grade 3 ◽

Combination Regimens

e16567 Background: ICI/TKI combinations are a new standard of care for the initial treatment (tx) of mRCC. Efficacy and toxicity of such combination regimens beyond the first-line (1L) setting remain unknown. Methods: We retrospectively reviewed charts for adult patients (pts) receiving an ICI/TKI combination in any line of tx for mRCC of any histology at one of two academic centers as of May 1, 2020. ICIs included pembrolizumab (Pm), nivolumab (Ni), ipilimumab (Ip), or avelumab (Av); TKIs included sunitinib (Su), axitinib (Ax), pazopanib (Pz), lenvatinib (Ln), or cabozantinib (Ca). Clinical data including pt demographics, histology, International mRCC Database Consortium (IMDC) risk group, tx history, and ICI/TKI tx and toxicity details were recorded. Outcomes included objective response rate (ORR), median progression-free survival (mPFS), and safety, analyzed via descriptive statistics and the Kaplan-Meier method. Results: Of 85 pts, 69 (81%) were male and 67 (79%) had clear cell histology. IMDC risk was favorable (24%), intermediate (54%), poor (20%), and unknown (2%). 39% had ICI/TKI tx in the 1L setting. ICI/TKI regimens included Pm/Ax (33%), Ni/Ca (25%), Ni/Ax (20%), Av/Ax (11%), Ni/Ip/Ca (8%), Ni/Su (2%), and Ni/Ln (1%). ORR and mPFS stratified by line of tx and prior tx are shown in the table. Of 52 pts who received ICI/TKI tx as salvage (after 1L), 52% had a grade 3 or higher (≥G3) adverse event (AE), of which the most common were anorexia (13.5%), diarrhea and hypertension (11.5% each), and fatigue (9.6%). 65% of pts on salvage ICI/TKI tx stopped tx for progression/death, while 16% stopped tx for ≥G3 AE. ≥G3 AE rates by line of tx were 62.5% (2L), 50% (3L), and 45% (≥4L). Conclusions: ICI/TKI combination therapy is effective and safe beyond the 1L setting. Prior tx history appears to impact efficacy but has less of an effect on safety/tolerability. These observations will need to be confirmed in prospective studies.[Table: see text]

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Olaparib plus paclitaxel in patients with recurrent or metastatic gastric cancer: A randomized, double-blind phase II study.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.15_suppl.4013 ◽

2013 ◽

Vol 31 (15_suppl) ◽

pp. 4013-4013 ◽

Cited By ~ 22

Author(s):

Yung-Jue Bang ◽

Seock-Ah Im ◽

Keun-Wook Lee ◽

Jae Yong Cho ◽

Eun-Kee Song ◽

...

Keyword(s):

Gastric Cancer ◽

Parp Inhibitor ◽

Objective Response ◽

Progression Free Survival ◽

Metastatic Gastric Cancer ◽

Double Blind ◽

Protein Levels ◽

Common Grade ◽

Atm Protein ◽

Grade 3

4013 Background: Our multicenter study compared the efficacy of the oral PARP inhibitor olaparib plus paclitaxel (O/P) vs paclitaxel alone (P) as second-line therapy in pts with recurrent/metastatic gastric cancer (GC) (NCT01063517). As initial preclinical data suggested that responsiveness of GC cell lines to olaparib was associated with low ATM protein levels, our study was enriched for pts with low ATM tumors (ATM–) by IHC (50% randomized vs 14% screening prevalence). Methods: Eligible pts were randomized 1:1 (stratified by ATM status) to receiveolaparib 100 mg bid (tablet form) plus paclitaxel (80 mg/m2 iv on days 1, 8, 15 per 28-day cycle) or placebo plus paclitaxel until progression or investigator decision. After combination therapy, pts could take olaparib 200 mg bid monotherapy or placebo until progression. Co-primary endpoints: progression-free survival (PFS; RECIST v1.1) in all pts and ATM– pts. Secondary endpoints: overall survival (OS), objective response rate (ORR), safety. Results: 123/124 randomized pts were treated (O/P=61; P=62). Baseline characteristics were generally well balanced. Use of post-progression therapy was similar in both arms (O/P=48.4%; P=43.5%) as was median paclitaxel duration (O/P=17 wks; P=16 wks); 18 pts received monotherapy (O/P=11; P=7). More pts in the O/P than P arm had delays (79 vs 63%) and reductions (41 vs 27%) in paclitaxel dosing. The most common grade ≥3 AEs in the O/P and P arms were neutropenia (56 vs 39%) and anemia (11 vs 11%). Conclusions: Olaparib plus paclitaxel was well tolerated and led to a statistically significant improvement in OS, but not PFS, vs paclitaxel alone in both all pts and ATM– pts, with a larger benefit in ATM– pts. Clinical trial information: NCT01063517. [Table: see text]

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Third- and later-line treatment in advanced or metastatic gastric cancer: a systematic review and meta-analysis

Future Oncology ◽

10.2217/fon-2019-0429 ◽

2020 ◽

Vol 16 (2) ◽

pp. 4409-4418 ◽

Cited By ~ 4

Author(s):

Alessandro Rizzo ◽

Veronica Mollica ◽

Angela Dalia Ricci ◽

Ilaria Maggio ◽

Maria Massucci ◽

...

Keyword(s):

Gastric Cancer ◽

Systematic Review ◽

Overall Survival ◽

Supportive Care ◽

Meta Analysis ◽

Objective Response ◽

Progression Free Survival ◽

Metastatic Gastric Cancer ◽

Best Supportive Care ◽

Free Survival

Aim: We performed a systematic review and meta-analysis to investigate the efficacy and safety of third-line (TLT) and salvage treatment (ST) in advanced or metastatic gastric cancer. Materials & methods: Eligible studies included randomized clinical trials assessing TLT and ST versus placebo or best supportive care. Outcomes of interest included: overall survival, objective response rate and disease control rate in TLT; progression-free survival in ST; grade 3–4 adverse events in ST. Results: The use of TLT and ST was superior to placebo or best supportive care in terms of prolonging overall survival and progression-free survival. Hematological toxicities were more frequent in ST. Conclusion: TLT and ST are considerable and tolerable treatment options for patients with advanced or metastatic gastric cancer. Given the substantial heterogeneities affecting the efficacy analyses, these results have to be interpreted cautiously.

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Retrospective cohort study of nanoparticle albumin-bound paclitaxel plus ramucirumab versus paclitaxel plus ramucirumab as second-line treatment in patients with advanced gastric cancer

BMC Cancer ◽

10.1186/s12885-020-07614-6 ◽

2020 ◽

Vol 20 (1) ◽

Author(s):

Mashiro Okunaka ◽

Daisuke Kotani ◽

Ken Demachi ◽

Akihito Kawazoe ◽

Takayuki Yoshino ◽

...

Keyword(s):

Gastric Cancer ◽

Advanced Gastric Cancer ◽

Progression Free Survival ◽

Similar Efficacy ◽

Hazard Ratio ◽

Line Treatment ◽

Second Line ◽

Efficacy And Safety ◽

Free Survival ◽

Grade 3

Abstract Background Nanoparticle albumin-bound paclitaxel (nab-PTX) has shown non-inferiority to paclitaxel (PTX) as second-line therapy for advanced gastric cancer (AGC) with fewer infusion-related reactions. The efficacy and safety of nab-PTX plus ramucirumab (RAM) was reported in a phase II trial; however, there is no randomized trial comparing this regimen with PTX plus RAM in patients with AGC. This retrospective study aimed to investigate the efficacy and safety of nab-PTX plus RAM versus PTX plus RAM in patients with AGC. Methods This study included patients with AGC who received nab-PTX plus RAM from September 2017 to January 2019 or PTX plus RAM from June 2015 to August 2017 as second-line chemotherapy in our hospital. Results A total of 113 and 138 patients who received nab-PTX plus RAM and PTX plus RAM, respectively, were analyzed. Median progression-free survival (PFS) was 3.9 months (95% confidence interval [CI]: 3.4–4.3) in the nab-PTX plus RAM group and 3.9 months (95% CI: 3.1–4.7) in the PTX plus RAM group (hazard ratio [HR]: 1.08; 95% CI: 0.83–1.40; P = 0.573). Median overall survival (OS) was 10.9 months (95% CI: 9.3–12.7) in the nab-PTX plus RAM group and 10.3 months (95% CI: 8.5–12.0) in the PTX plus RAM group (hazard ratio: 0.82; 95% CI: 0.61–1.10; P = 0.188). In patients with moderate/massive ascites, favorable outcomes for progression-free survival were observed in the nab-PTX plus RAM group compared with the PTX plus RAM group. Although anemia and fatigue (any grade) were more frequent in the nab-PTX plus RAM group, discontinuation of study treatment was not increased in the nab-PTX plus RAM group. There was no occurrence of hypersensitivity reaction in the nab-PTX plus RAM group, while two patients (1.4%) experienced grade 3 hypersensitivity reactions in the PTX plus RAM group. Conclusions The combination of nab-PTX plus RAM showed a similar efficacy and safety profile to PTX plus RAM as second-line treatment for patients with AGC.

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The efficacy and safety of apatinib treatment for patients with advanced or recurrent biliary tract cancer: a retrospective study

BMC Cancer ◽

10.1186/s12885-021-07907-4 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Caiyun Nie ◽

Huifang Lv ◽

Yishu Xing ◽

Beibei Chen ◽

Weifeng Xu ◽

...

Keyword(s):

Overall Survival ◽

Combination Therapy ◽

Biliary Tract ◽

Biliary Tract Cancer ◽

Objective Response ◽

Progression Free Survival ◽

Efficacy And Safety ◽

Free Survival ◽

Tract Cancer ◽

Systemic Therapies

Abstract Introduction The present study aims to evaluate the efficacy and safety of apatinib monotherapy or combination therapy for patients with advanced or recurrent biliary tract cancer (BTC). Methods Twenty-eight patients with advanced or recurrent BTC who progressed after prior systemic therapies and treated with apatinib from January 2017 to June 2019 were enrolled in this retrospective and observational study. The primary end point was progression free survival (PFS). Secondary end points included overall survival (OS), objective response rate (ORR), disease control rate (DCR), and toxicity. Results A total of 28 patients with advanced or recurrent BTC who progressed after prior systemic therapies received apatinib monotherapy or combination therapy (with capecitabine, S-1, oxaliplatin, irinotecan or PD-1 inhibitor), including 9 cases of gallbladder cancer and 19 cases of cholangiocarcinoma. Six patients achieved PR, 15 patients had SD and 7 patients had PD. Median progression-free survival (PFS) and overall survival (OS) was 4.3 months (95%CI = 1.8–6.8) and 6.2 months (95% CI = 4.6–7.8) respectively. The ORR and DCR were 21.4% (6/28) and 75.0% (21/28), respectively. Most of the adverse events were grade 1–2 in severity, apatinib treatment was well tolerated. Conclusions Apatinib monotherapy or combination therapy can improve PFS in patients with advanced or recurrent BTC who progressed after prior systemic therapies, and adverse reactions can be well tolerated. Our study support apatinib therapy as a feasible therapeutic strategy in advanced or recurrent BTC.

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The Efficacy and Safety of Apatinib Treatment for Patients with Advanced or Recurrent Biliary Tract Cancer: A Retrospective Study

10.21203/rs.3.rs-61633/v1 ◽

2020 ◽

Author(s):

Caiyun Nie ◽

Huifang Lv ◽

Yishu Xing ◽

Beibei Chen ◽

Weifeng Xu ◽

...

Keyword(s):

Overall Survival ◽

Combination Therapy ◽

Biliary Tract ◽

Biliary Tract Cancer ◽

Objective Response ◽

Progression Free Survival ◽

Efficacy And Safety ◽

Free Survival ◽

Tract Cancer ◽

Systemic Therapies

Abstract Background The present study aims to evaluate the efficacy and safety of apatinib monotherapy or combination therapy for patients with advanced or recurrent biliary tract cancer(BTC). Methods Twenty-eight patients with advanced or recurrent BTC who progressed after prior systemic therapies and treated with apatinib from January 2017 to June 2019 were enrolled in this retrospective and observational study. The primary end point was progression free survival (PFS). Secondary end points included overall survival (OS), objective response rate (ORR), disease control rate (DCR), and toxicity. Results A total of 28 patients with advanced or recurrent BTC who progressed after prior systemic therapies received apatinib monotherapy or combination therapy, including 9 cases of gallbladder cancer and 19 cases of cholangiocarcinoma. 6 patients achieved PR, 15 patients had SD and 7 patients had PD. Median progression-free survival (PFS) and overall survival (OS) was 4.3 months(95%CI = 1.8–6.8) and 6.2 months(95% CI = 4.6–7.8) respectively. The ORR and DCR were 21.4% (6/28) and 75.0% (21/28), respectively. Most of the adverse events were grade 1–2 in severity, apatinib treatment was well tolerated. Conclusions Apatinib monotherapy or combination therapy can improve PFS in patients with advanced or recurrent BTC who progressed after prior systemic therapies, and adverse reactions can be well tolerated. Our study support apatinib therapy as a feasible therapeutic strategy in advanced or recurrent BTC.

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Retrospective cohort study of nanoparticle albumin-bound paclitaxel plus ramucirumab versus paclitaxel plus ramucirumab as second-line treatment in patients with advanced gastric cancer

10.21203/rs.3.rs-26226/v1 ◽

2020 ◽

Author(s):

Mashiro Okunaka ◽

Daisuke Kotani ◽

Ken Demachi ◽

Akihito Kawazoe ◽

Takayuki Yoshino ◽

...

Keyword(s):

Gastric Cancer ◽

Advanced Gastric Cancer ◽

Progression Free Survival ◽

Similar Efficacy ◽

Hazard Ratio ◽

Line Treatment ◽

Second Line ◽

Efficacy And Safety ◽

Free Survival ◽

Grade 3

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Toxicity and efficacy of FOLFIRI regimen and aflibercept combination in metastatic colorectal cancer: first results of a Russian multicenter retrospective study

Malignant tumours ◽

10.18027/2224-5057-0-0-0- ◽

2019 ◽

Vol 9 (2) ◽

pp. 53-63

Author(s):

M. Yu. Fedyanin ◽

L. Yu. Vladimirova ◽

V. A. Chubenko ◽

L. A. Zagorskaya ◽

A. V. Belyayeva ◽

...

Keyword(s):

Adverse Events ◽

Objective Response Rate ◽

Response Rate ◽

Objective Response ◽

Progression Free Survival ◽

Hematologic Toxicity ◽

Line Treatment ◽

Second Line ◽

Free Survival ◽

Grade 3

Purpose. To assess the incidence and severity of adverse events; to explore clinical factors associated with grade 3–4 non-hematologic toxicity; to assess the immediate efficacy and progression-free survival during treatment with the FOLFIRI regimen in combination with aflibercept in Russia.Materials and Methods. A retrospective multicenter study has been conducted with data collected from 20 clinics in 15 regions of Russia. There was no statistical hypothesis. Progression-free survival was the main efficacy criterion. The statistical analysis was performed using IBM SPPS Statistics v. 20 software.Results. FOLFIRI and Aflibercept combination was administered to 264 patients. The mean number of treatment cycles was 6 (1 to 29). The toxicity of aflibercept was addressed by dose reduction and dosing delay in 10.1 % and 11.4 % of patients, respectively, and dose reductions and dosing delays in any of FOLIFRI components were reported in 20.1 % of participants. The objective response rate was 20.3 %. The median progression-free survival in patients receiving second-line treatment was 6 months (95 % CI: 5.3–6.6 months). Seventy-two percent of patients experienced any grade of adverse events most of which were limited to grade 1–2 (62.1 %). Non-hematologic toxicity was reported in 64 % of patients (grade 3–4 in 17.9 %). Hematologic events were detected in only 17.9 % of patients. Multifactorial analysis has shown that drug therapy for concomitant diseases (OR 1.98, 95 % CI: 1.04–3.78, p = 0.037) and the number of chemotherapy lines prior to aflibercept (ОR 1.5, 95 % CI: 1.06–2.11, p = 0.02) were independent predictors of grade 3–4 non-hematologic toxicity.Conclusions. Objective response rate, progression-free survival, and frequency of toxicity-related aflibercept discontinuations in the Russian study with patients receiving aflibercept in combination with FOLFIRI regimen as a second-line treatment has shown the results that were comparable with VELOUR study. Comorbidities requiring drug treatment and the number of prior chemotherapy lines appear to be risk factors for grade 3–4 nonhematological toxicity events.

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Antitumor activity of margetuximab (M) plus pembrolizumab (P) in patients (pts) with advanced HER2+ (IHC3+) gastric carcinoma (GC).

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.4_suppl.65 ◽

2019 ◽

Vol 37 (4_suppl) ◽

pp. 65-65 ◽

Cited By ~ 7

Author(s):

Daniel V.T. Catenacci ◽

Kian Huat Lim ◽

Hope Elizabeth Uronis ◽

Yoon-Koo Kang ◽

Matthew C.H. Ng ◽

...

Keyword(s):

Gastroesophageal Junction ◽

Objective Response ◽

Progression Free Survival ◽

Circulating Tumor Dna ◽

Second Line ◽

Her2 Expression ◽

Free Survival ◽

First Line Therapy ◽

Gastroesophageal Adenocarcinoma ◽

Grade 3

65 Background: Trastuzumab (T) + chemo is standard first-line therapy (tx) for HER2+ gastroesophageal adenocarcinoma (GEA) pts, though progression ensues in 6-8 months. The approved second-line tx is ramucirumab +/- paclitaxel (R+PAC). Pts with GC are less responsive to R+PAC than gastroesophageal junction (GEJ) pts, in particular HER2+ GC, and no anti-HER2 agents are approved in post-T setting. We report results of combination M+P in HER2+ GC pts and describe a biological rationale for this population. M is an anti-HER2 mAb Fc optimized for enhanced binding to activating FcgRIIIa (CD16A) and decreased binding to inhibitory FcgRIIb (CD32B). M demonstrated an enhanced Fc-dependent MoA, including enhanced ADCC. Methods: HER2+, PD-L1-unselected, second-line GEA pts post T progression received M (15 mg/kg) + P (200 mg) Q3wk. Safety, objective response rate (ORR), median overall & progression-free survival (mOS, mPFS), disease control rate (DCR), circulating tumor DNA, & tumor PD-L1 expression were assessed. Results: To date, 66 GEA pts were dosed; 35 (53%) GC and 31 (47%) GEJ. Overall, 12/66 (18.2%) had tx-related adverse events ≥ grade 3; 5 had drug-related SAEs: dehydration, diabetic ketoacidosis, hypotension and pneumonitis, each a single event, and 2 events of autoimmune hepatitis. Eligibility was based on archival HER2 expression; an exploratory endpoint measured retention of HER2 expression post-T by ERBB2 ctDNA. HER2 expression was lost in 23/56 (41.1%) of pts tested post T. HER2 retention was higher in pts with GC versus GEJ (65.8% vs. 44.8%) and in GEA pts with IHC 3+ vs 2+ archival tumors (61.7% vs 47.4%, respectively). Furthermore, GC had higher PD-L1 expression than GEJ, 53.3 vs. 33.3%, respectively. This coincided with more responses in IHC3+ GC pts, ORR 12/29 (41.4%; 95% CI 23.5-61.1), DCR 21/29 (72.4%; 95% CI 52.8-87.3), mPFS 5.5 months (95% CI 2.3-7.6), mOS not reached, with lower bound of 9.1 months for 95% CI. Enrollment of an additional 25 pts enriched for IHC3+ GC is ongoing. Conclusions: Results suggest that M+P, a chemo-free regimen, demonstrates acceptable tolerability and has encouraging preliminary activity in second-line HER2+ GEA, specifically in GC pts who retain ERBB2 amp prior to second-line tx. Clinical trial information: NCT02689284.

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Irinotecan Plus Mitomycin C as Second-Line Chemotherapy for Advanced Gastric Cancer Resistant to Fluoropyrimidine and Cisplatin: A Retrospective Study

Gastroenterology Research and Practice ◽

10.1155/2012/640401 ◽

2012 ◽

Vol 2012 ◽

pp. 1-5 ◽

Cited By ~ 1

Author(s):

Kohei Ogawa ◽

Ayumu Hosokawa ◽

Akira Ueda ◽

Seiko Saito ◽

Hiroshi Mihara ◽

...

Keyword(s):

Gastric Cancer ◽

Advanced Gastric Cancer ◽

Mitomycin C ◽

Median Overall Survival ◽

Overall Response Rate ◽

Progression Free Survival ◽

Second Line ◽

Free Survival ◽

Grade 3 ◽

Line Chemotherapy

Background. S-1 plus cisplatin has been established to be standard first-line chemotherapy for advanced gastric cancer in Japan. The optimal second-line treatment refractory to S-1 plus cisplatin remains unclear.Methods. We retrospectively studied the efficacy, toxicity, and survival of irinotecan plus mitomycin C in patients with advanced gastric cancer refractory to a fluoropyrimidine plus cisplatin.Results. Twenty-four patients were studied. Prior chemotherapy was S-1 plus cisplatin in 15 patients, S-1 plus cisplatin and docetaxel in 8, and 5-fluorouracil plus cisplatin with radiotherapy in 1. The overall response rate was 17.4%. The median overall survival was 8.6 months, and the median progression-free survival was 3.6 months. Grade 3 or 4 toxicities included leukopenia (33%), neutropenia (50%), anemia (33%), thrombocytopenia (4%), anorexia (13%), diarrhea (4%), and febrile neutropenia (13%).Conclusion. A combination of irinotecan and mitomycin C is potentially effective in patients with advanced gastric cancer refractory to a fluoropyrimidine plus cisplatin.

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