scholarly journals Neutrophil-to-Lymphocyte Ratio (NLR) Predicts PD-1 Inhibitor Survival in Patients with Metastatic Gastric Cancer

2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Miaomiao Gou ◽  
Tongtong Qu ◽  
Zhikuan Wang ◽  
Huan Yan ◽  
Yanhai Si ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Response Rate ◽  
Univariate Analysis ◽  
Objective Response ◽  
Progression Free Survival ◽  
Metastatic Gastric Cancer ◽  
Neutrophil To Lymphocyte Ratio ◽  
Lymphocyte Ratio ◽  
Significant Difference ◽  
Formula Group

Background and Aims. Biomarkers for systemic inflammation have been introduced into clinical practice for risk-rating in cancer patients’ treatment. This study is aimed at confirming the prognostic role of the neutrophil-to-lymphocyte ratio (NLR) as an effective biomarker for patients with metastatic gastric cancer (MGC) receiving anti-PD-1 agents. Method. Patients with MGC who received anti-PD-1 treatment at the Chinese PLA General Hospital between January 2016 and November 2020 were reviewed. The study analyzed the association of NLR and overall survival (OS) or progression-free survival (PFS) and antitumor response rate with PD-1 inhibitors. Results. 137 patients were included in the final analysis. The area under the curve value of NLR for 6-month OS was 0.71. The best cut-off value for NLR was 3.23. NLR < 3.23 was associated with longer OS ( HR = 0.38 , 95% CI, 0.26-0.57, p < 0.001 ) and PFS ( HR = 0.42 , 95% CI, 0.29-0.62, p < 0.001 ) in patients with MGC. No significant difference was observed in the objective response rate (ORR) (35.8% vs. 28.6%, p = 0.377 ) and disease control rate (DCR) (86.4% vs. 78.6%, p = 0.229 ) in the NLR < 3.23 group and in the NLR ≥ 3.23 group, respectively. Univariate analysis and multivariate analysis found that NLR was an independent prognosis biomarker for PFS and OS. Conclusions. Pretreatment elevated NLR was significantly associated with inferior PFS and OS in patients with MGC who received anti-PD-1 inhibitors. Clinicians need to consider patients with elevated NLR for decisions on immunotherapy strategy.

Neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR) and hemoglobin (Hb) predict immunotherapy outcomes in patients with advanced or metastatic gastric cancer.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e16075-e16075
Author(s):  
Miaomiao Gou ◽  
Yong Zhang ◽  
Huan Yan ◽  
Haiyan Si ◽  
Zhikuan Wang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Response Rate ◽  
Objective Response ◽  
Progression Free Survival ◽  
Final Analysis ◽  
Metastatic Gastric Cancer ◽  
Neutrophil To Lymphocyte Ratio ◽  
Platelet To Lymphocyte Ratio ◽  
Lymphocyte Ratio ◽  
Significant Difference

e16075 Background: This study aimed to confirm the prognostic role of pretreatment neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), hemoglobin (Hb) levels as effective and convenient biomarkers for patients with advanced or metastatic gastric cancer (AGC or MGC) receiving immunotherapy. Methods: patients with AGC and MGC who received anti-PD-1 treatment at the Chinese PLA General Hospital between January 2016 and November 2020 were reviewed. The receiver operating characteristic analyses for predicting 6 months PFS by the NLR, PLR was used to identify an appropriate cut-off value. The study analyzed the association of NLR, PLR, Hb and overall survival (OS) or progression-free survival (PFS) and anti-tumor response rate with immunotherapy respectively. Results: 137 patients were included in the final analysis. 71 patients were administered immunotherapy in the first line and the rest of the patients in the second or further line. 92 patients had received immunotherapy combined with chemotherapy, whereas 45 patients had undertaken immunotherapy monotherapy or with anti-angiogenesis. The best cut-off value for NLR was 3.23 and for PLR was 816.43. NLR <3.23 was associated with longer OS (HR = 0.38, 95% CI, 0.26-0.57, p < 0.001) and PFS (HR = 0.42, 95% CI, 0.29-0.62, p < 0.001) in patients with AGC or MGC. Patients in PLR<816.43 group had prolonged PFS (7.9m vs 4.3m, p<0.001) and OS (11.1m vs9.2m, p<0.001) than in PLR>=816.43 group. The median PFS was 7.8m in the normal Hb level group (Hb>=110g/L) and 4.3m in the decreased Hb group (Hb<110g/L) (HR=0.5, 95% CI 0.31, 0.81, P=0.004). The OS was 14.4m with normal Hb level as compared with 8.2m with decreased Hb level( HR=0.59, 95% CI 0.37, 0.94, P=0.024). No significant difference was observed in objective response rate (ORR) and disease control rate (DCR) in the different NLR, PLR, Hb group, respectively. Univariate and multivariate analysis found that NLR, PLR, Hb were independent prognostic biomarkers for PFS and OS (p<0.05). Conclusions: pre-treatment NLR, PLR, Hb was significantly associated with PFS and OS in patients with AGC and MGC who received immunotherapy. Clinicians need to consider patients with elevated NLR and PLR or decreased Hb level for decisions on immunotherapy strategy.

scholarly journals Pretreatment Platelet-to-Lymphocyte Ratio (PLR) is associated with prognosis in gastric cancer patients with immunotherapy

2021 ◽  
Author(s):  
Miaomiao Gou ◽  
Yong Zhang
Keyword(s):  
Gastric Cancer ◽  
Response Rate ◽  
Univariate Analysis ◽  
Objective Response ◽  
Area Under The Curve ◽  
Progression Free Survival ◽  
Final Analysis ◽  
Platelet To Lymphocyte Ratio ◽  
Lymphocyte Ratio ◽  
Significant Difference

Abstract Background: previous studies had demonstrated that system inflammation indexes were associated with prognosis ability in various cancers. We aim to explore the prognostic value of platelet to lymphocyte ratio (PLR) in patients with advanced or metastatic gastric cancer (AGC or MGC) receiving immunotherapy. Method: patients with AGC and MGC who received anti-PD-1 treatment at the Chinese PLA General Hospital between January 2016 and August 2020 were reviewed. The study analyzed the association of PLR and overall survival (OS) or progression-free survival (PFS) and anti-tumor response rate with immunotherapy.Results: 137 patients were included in the final analysis. The area under the curve values of PLR for 6 months PFS was 0.68(P<0.05). The best cut-off value for PLR was 816.43. Patients in PLR <816.43 group had PFS of 7.9m compared to 4.3m in PLR>= 816.43 group (HR = 0.61`, 95% CI, 0.42-0.89, p < 0.001).OS in PLR <816.43 group was longer than PLR>= 816.43 group (11.1m vs 9.2m, HR = 0.62`, 95% CI, 0.42-0.93, p < 0.001). The objective response rate (ORR) and disease control rate (DCR) were 34.1% and 84.6% respectively in PLR <816.43 group while 30.4% and 80.4% in the>= 816.43 group. No significant difference was observed among two group in terms of ORR and DCR (p=0.669, p=0.536). Univariate analysis and multivariate analysis found that PLR was an independent prognosis biomarker for PFS and OS(p<0.05). Conclusions: Pre-treatment PLR was significantly associated with PFS and OS in patients with AGC and MGC who received immunotherapy. Clinicians might consider patients with elevated PLR as one factor for decisions on immunotherapy strategy.

scholarly journals The Prognostic Value of Pre-treatment Hemoglobin (Hb) in Patients With Advanced or Metastatic Gastric Cancer Treated With Immunotherapy

2021 ◽  
Vol 11 ◽  
Author(s):  
Miaomiao Gou ◽  
Yong Zhang ◽  
Tiee Liu ◽  
Tongtong Qu ◽  
Haiyan Si ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Multivariate Analysis ◽  
Prognostic Value ◽  
Univariate Analysis ◽  
Objective Response ◽  
Progression Free Survival ◽  
Metastatic Gastric Cancer ◽  
Significant Prognostic Factor ◽  
Angiogenic Therapy ◽  
Pre Treatment

BackgroundBiomarkers such as prevailing PD-L1 expression and TMB have been proposed as a way of predicting the outcome of immunotherapy in patients with advanced gastric cancer (AGC) and metastatic gastric cancer (MGC). Our study aims to investigate whether there is a link between pretreatment hemoglobin (Hb) levels and survival to immunotherapy in patients with AGC and MGC.MethodsWe retrospectively reviewed patients with AGC or MGC treated at the oncology department of the Chinese PLA general hospital receiving PD-1 inhibitor. The Propensity Score Matching (PSM) (1:1) was performed to balance potential baseline confounding factors. Progression-free survival (PFS) and overall survival (OS) was analyzed among different Hb level (normal Hb group and decreased Hb group). Objective response rate (ORR), disease control rate (DCR) were also analyzed. Univariate analysis and multivariate analysis were performed further to validate the prognostic value of Hb level.ResultsWe included 137 patients with AGC and MGC who received PD-1 inhibitors (including Pembrolizumab, Nivolumab, Sintilimab, Toripalimab) in this study. After PSM matching, there were no significant differences between the two groups for baseline characteristics. Within the matched cohort, the median PFS was 7.8 months in the normal Hb level group and 4.3 months in the decreased Hb group (HR 95% CI 0.5(0.31, 0.81), P=0.004). The OS was 14.4 months with normal Hb level as compared with 8.2 months with decreased Hb level(HR 95% CI 0.59(0.37, 0.94), P=0.024). The ORR was 40.7% and DCR was 83.0% in the normal Hb group, while the ORR was 25.5% and DCR was 85.1% in the decreased Hb group. No significant differences were found in the ORR and DCR between the two groups (P=0.127, P=0.779). Univariate analysis and multivariate analysis showed that Hb level was only independent predictor for PFS and baseline Hb level was significant prognostic factor influencing the OS. Only when patients had normal Hb level, anti-pd-1 monotherapy or combined with chemotherapy was superior to anti-pd-1 plus anti-angiogenic therapy with respect to PFS (10.3 m vs 2.8 m, HR 95% CI 0.37(0.15, 0.95), P=0.031) and OS(15 m vs 5.7 m, HR 95% CI 0.21 (0.08, 0.58), P=0.001).ConclusionsOur study have demonstrated that pretreatment Hb level was an independent prognostic biomarker in term of PFS and OS with immunotherapy for AGC and MGC patients. Correction of anemia for GC patients as immunotherapy would be a strategy to improve the survival. More data was warranted to further influence this finding.

When will it be better? Lenvatinib combined with TACE for unresectable hepatocellular carcinoma: A retrospective analysis of real-world evidence in China.

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 281-281
Author(s):  
Lan Zhang ◽  
Yanhong Wang ◽  
Ningling Ge ◽  
Yu-Hong Gan ◽  
ZhengGang Ren ◽  
...  
Keyword(s):  
Combination Treatment ◽  
Real World ◽  
Response Rate ◽  
Objective Response ◽  
Progression Free Survival ◽  
Combination Group ◽  
Optimal Timing ◽  
Real World Data ◽  
Combination Strategy ◽  
Significant Difference

281 Background: TACE and lenvatinib has each shown to prolong overall survival in patients with unresectable HCC, combination of which may also improve clinical outcomes and have been widely used in the real world accordingly. However, the optimal timing of adding on lenvatinb to TACE remains unclear. We are aiming to evaluate the efficacy and safety between two combination strategies. Methods: From Nov 2018 to Jun 2020, 79 consecutive patients had received a combination treatment of lenvatinib and TACE. Patients followed up for more than 2 months were included in this analysis. They were classified as early-combination group(add on lenvatinib before or after the first TACE ) and late-combination group(add on lenvatinib after at least two procedures of TACE ). Tumor response and progression-free survival (PFS,time from the first day of prescribing lenvatinib to progression or death) were assessed according to RECIST1.1 criteria. Liver function were also evaluated at baseline and every 2 months later. AEs were recorded during the combination treatment period according to CTCAE 5.0. Results: A total of 48 u-HCC patients was finally enrolled. Median follow-up in all patients was 9.3(5.3-14.3)months. Patients’ baseline characteristics were similar in two groups. For early-combination group(n=22)and late-combination group(n=26), the mean age was 65±9.7 and 61±11.6years(p=0.2);BCLC stage C HCC was 59% and 54%(p=0.89);and Child-Pugh A proportion was 81.8% and 77%(p=0.73) respectively. The objective response rate(ORR) was 22.9% in total 48 cases. There was no significant difference in response rate (18.2% vs 26.9%, P=0.51) or disease control rate (90.9% vs 92.3%, P=1.00). Median PFS was significantly longer in the early-combination group than that in late-combination group (14.5 vs 8.9 months; p=0.048). The safety profile was similar between two groups. Grade 3/4 adverse events were 3 (13.6%) and 2 cases(7.7%) respectively (P=0.65). Conclusions: This is to date the first real-world data of the combination timing of lenvatinib with TACE in u-HCC patients. Early-combination strategy may be a better option for the u-HCC patients with a longer mPFS.

A phase II, multicenter, randomized, open-label study to evaluate the safety and tolerability of proxalutamide (GT0918) in subjects with metastatic castrate-resistant prostate cancer (mCRPC).

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 108-108
Author(s):  
Tie Zhou ◽  
Dingwei Ye ◽  
Zhongquan Sun ◽  
Qinggui Meng ◽  
Dalin He ◽  
...  
Keyword(s):  
Dose Level ◽  
Response Rate ◽  
Objective Response ◽  
Specific Antigen ◽  
Stage Iv ◽  
Study Drug ◽  
Progression Free Survival ◽  
Open Label ◽  
Significant Difference ◽  
Psa Progression

108 Background: GT0918 is a 2nd generation of AR antagonist and capability to down-regulate AR level. This study is an open-label, randomized, multicenter, Ph II study to evaluate the safety and efficacy in patients with mCRPC, and to determine the optimal dose for Ph III study. Methods: Patients with historically confirmed mCRPC who progressed after/intolerant to/reluctant to receive Docetaxel and previously treated with abiraterone or enzalutamide were excluded. All the patients received up to 6 cycles or, unacceptable toxicity, or loss of clinical benefit as recommended by PCWG3. Primary endpoint was prostate-specific antigen (PSA) reduction from baseline. Secondary endpoints included time to PSA progression (TTPP), objective response rate (ORR), progression free survival (PFS), disease control rate (DCR) and safety profiles. Results: As of June 30, 2019, 108 treated with GT0918 at three dose levels: 100 mg (n =37), 200 mg (n = 35) and 300 mg (n = 36), the median age of patients was 70.0 years (range 63-77), 88% of patients had stage IV disease at the initial diagnosis and 69.4% had Gleason score ≥ 8. The median duration of disease was 2.88 years. All received prior endocrine therapy, 35.2% received prior chemotherapy, 29.6% received Docetaxel. The median PSA at baseline was 35.285ng/ml, PSA response rate (≥50 % reduction from baseline) was 41.9%. The median time to PSA progression was not reached. There was no significant difference among three arms. Of 19 evaluable patients with target lesions at baseline, the ORR was 15.8% (all were PR) assessed by IRC with RECIST v 1.1, with 20.0% (1/5), 22.2% (2/9), 0 (0/5) at 100, 200, 300 dose level, respectively. The DCR assessed by IRC was 78.9% (CR 0+PR15.8%+SD 63.2%). Of 26 evaluable patients with target lesions at baseline, the ORR was 19.2% assessed by investigators (CR 3.8%+PR 15.4%), with 11.1% (1/9), 20.0% (2/10), 28.6% (2/7) at 100, 200, 300 dose level, respectively. Overall, AEs were experienced by most of patients (94.4 %, n=102). AEs leading to drug interruption were reported in 13 patients (12.0%), 9 (8.3%)of them were suspected to be drug related. AEs leading to discontinuation were reported in 6 patients (5.6%), 3(2.8%) were possibly related to GT0918. 14 patients (13.0%) experienced Grade 3 and 4 AEs. 17 patients (15.7%)experienced SAE, 5(4.6%) of them were suspected to be related to study drug. Most of AEs were mild or moderate. The common suspected AE (≥10%) were asthenia (17.6%, n=19), anemia (14.8%, n=16), AST increased (14.8%, n=16), ALT increased (13.0%, n=14), decreased appetite (13.0%, N=14), white blood cell count decreased (12.0%, n=13), proteinuria (12.0%, n=13). Conclusions: GT0918 showed a manageable safety profile. This study provided preliminary anti-tumor activity in patients with mCRPC. 200mg/day is recommended dose for Ph III trial. Clinical trial information: CTR20170177.

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

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 4013-4013 ◽  
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]

The prognostic value of systemic inflammatory factors in patient with metastatic gastric cancer.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e15505-e15505 ◽  
Author(s):  
Georgy M. Manikhas ◽  
Natalia P. Beliak ◽  
Svetlana I. Kutukova ◽  
Natalia V. Zhukova ◽  
Natalia V. Popova ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Overall Survival ◽  
Inflammatory Markers ◽  
Prognostic Biomarker ◽  
Metastatic Gastric Cancer ◽  
Neutrophil To Lymphocyte Ratio ◽  
C Reactive Protein ◽  
Platelet To Lymphocyte Ratio ◽  
Lymphocyte Ratio ◽  
Reactive Protein

e15505 Background: Inflammation seems to be significant factor in carcinogenesis and tumor progression of numerous cancers. Blood calculated neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), C-reactive protein (CRP), lactate dehydrogenase (LDH), international normalized ratio (INR) can be evaluated as systemic inflammation markers and prognostic biomarker for many aims: survival outcomes, lymph node metastasis and recurrence, treatment responses in a variety of cancers. The purpose of this study was to investigate baseline associations between blood test parameters (NLR, PLR, LDH, CRP, INR) and their prognostic biomarker role for patient with metastatic gastric cancer, undergoing first-line chemotherapy Methods: Potential baseline inflammatory markers (platelets, neutrophils, lymphocytes, the platelet-lymphocyte ratio, the neutrophil-lymphocyte ratio, the serum C-reactive protein [CRP], the serum LDH, INR) were retrospectively analyzed in 32 patients with metastatic gastric cancer, IV stage (median of age – 60,50). Multivariate analyses were used to identify prognostic factors for overall survival (OS). Baseline values were compared with tumor characteristic and median survival times (MSTs). Results: Multivariate analysis identified due to Cox proportional-hazards regression showed significant longest OS in patients with: localization of primary tumor in antral part of gastric (HR 0,45, 95% CI 0,25-0,80, p = 0,0065); low baseline’s level of WBC (HR 1,17, 95% CI 1.02 - 1,35, p = 0,0219); low baseline’s level of neutrophil (HR 1,18, 95% CI 1.02 - 1,34, p = 0,0251). Level of LDH, CRP, INR didn’t show significant ratio for this cohort of patient. Peritoneum metastatic also didn’t significant affect on OS in patient with metastatic gastric cancer. Patients with low baseline’s platelet to lymphocyte ratio (HR 1,004, 95% CI 1,0009-1,0072, p = 0,0125) and low (from 0 to 3,0) neutrophil to lymphocyte ratio (HR 1,81, 95% CI 1,09-2,99, p = 0,0212) had a significantly longest OS time. Conclusions: Inflammatory markers can predict overall survival in stage IV gastric cancer. Simple and useful.

Comparison of efficacy of aspirin plus epirubicin, oxaliplatin, and capecitabine versus epirubicin, oxaliplatin, and capecitabine alone in patients with locally advanced and metastatic gastric cancer: A randomized clinical trial.

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 384-384
Author(s):  
Esha Jafa ◽  
Biswajit Dubashi ◽  
Smita Kayal ◽  
Vikram Kate ◽  
Rajesh Nachiappa Ganesh ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Clinical Trial ◽  
Protocol Analysis ◽  
Locally Advanced ◽  
Progression Free Survival ◽  
Response Rates ◽  
Complete Response ◽  
Metastatic Gastric Cancer ◽  
Response To Treatment ◽  
Significant Difference

384 Background: Aspirin was long known to prevent cancer, the last decade revealed its therapeutic role via varied mechanisms like inhibition of platelet activation, COX and PI3K pathway. Since PI3K/AKT/mTOR is one of the pathways activated in gastric cancer and Giampieri et al (2016) showed improved response rates, PFS and OS with addition of aspirin to capecitabine in heavily pretreated metastatic colorectal cancer,a cancer in which efficacy of aspirin is related to presence of PI3K mutations,we aimed to compare the efficacy of aspirin added to a standard regime EOX with EOX alone in locally advanced and metastatic gastric cancer. Methods: All patients with advanced gastric cancer coming to JIPMER,Department of Medical oncology between march 2017 to may 2019 were screened for eligibility in the trial.Those eligible were randomly assigned to standard EOX or standard EOX plus 150 mg of daily aspirin.Tumor measurements were performed at baseline,then after 3-4 cycles (interim response) and the response to treatment was assessed by the radiologist who was blinded to treatment arms according to RECIST1.1 criteria.Toxicity profiles were recorded as per CTCAE v 4.03.In per protocol analysis,response rates, PFS(progression free survival) and OS (overall analysis) were analysed for patients who received ≥3 cycles and had an evaluable interim response. Results: 95 patients were randomised.In per protocol analysis, 70 patients were included. The results are shown in table. Conclusions: No statistically significant difference was seen with respect to response rates, PFS, OS and toxicity, although there was a higher ORR (overall response rate=complete response,CR +partial response, PR) and OS seen in EOX plus aspirin arm. Clinical trial information: CTRI/2017/11/010651. JIPMER,Puducherry,India [Table: see text]

Updated results from a phase Ib trial of regorafenib plus nivolumab in patients with advanced colorectal or gastric cancer (REGONIVO, EPOC1603).

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 135-135
Author(s):  
Kohei Shitara ◽  
Hiroki Hara ◽  
Naoki Takahashi ◽  
Takashi Kojima ◽  
Akihito Kawazoe ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Phase 1 ◽  
Randomized Study ◽  
Objective Response ◽  
Progression Free Survival ◽  
Maximum Tolerated Dose ◽  
Dose Finding ◽  
Significant Difference ◽  
One Year ◽  
Anti Tumor Activity

135 Background: In the phase 1 REGONIVO study, regorafenib of 80 mg/day plus nivolumab showed manageable safety profiles and encouraging anti-tumor activity for advanced colorectal cancer (CRC) or gastric cancer (GC) with objective response rate (ORR) of 36% in CRC and 44% in GC (Fukuoka, et al. ASCO 2019). Updated efficacy results are presented. Methods: Enrolled patients (pts) received regorafenib plus nivolumab in a dose-finding phase to estimate the maximum tolerated dose (MTD). Additional pts were enrolled in a dose-expansion phase. Regorafenib of 80 to 160 mg was administered once daily for 21 on 7 days off with nivolumab 3 mg/kg every 2 weeks. The primary endpoint was dose-limiting toxicity (DLT) during cycle one to estimate the MTD and the recommended dose. PD-L1 combined positive score (CPS) was assessed using the anti–PD-L1 28-8 antibody. Tumor mutation burden (TMB) was measured using Oncomine tumor mutation load assay. Results: Fifty pts were enrolled (25 CRC; 25 GC) until October 2018 with median prior treatment line of 3. Efficacy results were updated as of September 1st 2019. One CRC pt was with MSI-high but all other pts were with MSS or MMR-proficient. Among the 20 pts (9 CRC and 11 GC) with objective response (40%), responses are still ongoing in 13 pts (7 CRC and 6 GC) and the median duration of response was not reached (NR). Median progression free survival (PFS) was 7.8 months in CRC (95% CI, 2.8- NR) and 5.5 months (95% CI, 2.6-10.2 months) in GC. One-year PFS rate was 41.7% in CRC and 22.4% in GC. Median overall survival (OS) was not reached in CRC (95% CI, 9.7-NR) and 12.1 months (95% CI, 5.2-NR) in GC. One-year OS rate was 68% in CRC and 55.3% in GC. No significant difference of PFS and ORR was observed in CRC according to PD-L1 and TMB. Conclusions: Encouraging anti-tumor activity of the combination of regorafenib plus nivolumab had been maintained with long-term follow-up. A randomized study for MSS CRC is under planning. Clinical trial information: NCT03406871.

A phase Ib study of alofanib, an allosteric FGFR2 inhibitor, in patients with advanced or metastatic gastric cancer.

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. TPS466-TPS466
Author(s):  
Galina Statsenko ◽  
Mikhail Fedyanin ◽  
Vladimir Moiseyenko ◽  
Liubov Yu Vladimirova ◽  
Ilya Tsimafeyeu ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Standard Dose ◽  
Objective Response ◽  
Growth Factor Receptor ◽  
Progression Free Survival ◽  
Metastatic Gastric Cancer ◽  
Maximum Tolerated Dose ◽  
Inhibitory Effect ◽  
Pharmacokinetic Parameters ◽  
And Function

TPS466 Background: Fibroblast growth factor receptor 2 (FGFR2) is amplified or overexpressed in 3% to 61% of patients with gastric cancer and associated with a poor prognosis. Acquired mutations in FGFR2 develop resistance to multikinase inhibitors. Besides, resistance to monoclonal antibodies depends on the type of FGFR2 isoforms IIIc or IIIb expressed by cancer cells. Alofanib (RPT835) is a novel selective allosteric inhibitor of FGFR2. Alofanib could bind to the non-active site of FGFR2 extracellular domain and had an inhibitory effect on FGF2-induced phosphorylation of FRS2α. On preclinical models no severe organ and function test changes were observed. Based on these results, alofanib has advanced into clinical evaluation. Methods: RPT835GC1B is a Phase 1b study, being conducted in at least four sites in Russia, evaluating the safety and preliminary efficacy of alofanib in patients with advanced and metastatic gastric adenocarcinoma pretreated with ≥ 1 previous lines of therapy. This trial consists of two parts. The standard dose-escalation part (design 3+3) aims to establish the maximum tolerated dose (MTD) or recommended phase 2 dose (R2PD) as a primary endpoint. The first part of the study includes a 28-day period when alofanib is administered daily intravenously for 5-days followed by a 2-day interval (rest). There are five dose levels: 50, 100, 165, 250, and 350 mg/m2. The dose-expansion phase accrues additional 20 patients, where comprehensive information to be collected. Secondary endpoints include pharmacokinetic parameters, rate of adverse events, progression-free survival, overall survival, and objective response rate. All patients will receive alofanib until disease progression or unacceptable toxicity. FGFR2 amplification, fusion, and overexpression will be assessed as well. Clinical trial information: NCT04071184.

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