Efficacy and safety of PD-1/PD-L1 and CTLA-4 immune checkpoint inhibitors in colorectal cancer: a meta-analysis

2022 ◽  
Author(s):  
Chunhui Jin ◽  
Xiaodan Zhu ◽  
Xiaona Huang ◽  
Tingjie Gong ◽  
Zhipeng Wei ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Survival Rate ◽  
Mismatch Repair ◽  
Checkpoint Inhibitors ◽  
Meta Analysis ◽  
Objective Response ◽  
Progression Free Survival ◽  
Adverse Event Rate ◽  
Efficacy And Safety ◽  
Deficient Mismatch Repair

Aims: To evaluate the efficacy and safety of PD-1/PD-L1 and/or CTLA-4 inhibitors in the treatment of colorectal cancer (CRC) by meta-analysis. Methods: Electronic databases were searched. Eligible studies included investigations of efficacy and safety of anti-PD-1/PD-L1 or anti-CTLA-4 agents in patients with CRC. Corresponding indicators were calculated. Results: A total of 15 articles were included. The pooled objective response rate, overall survival rate, progression-free survival rate and adverse event rate were 33, 56, 46 and 59%, respectively. The objective response rates for CRC with deficient mismatch repair and CRC with proficient mismatch repair were 43 and 3%, respectively, in patients treated with PD-1 inhibitors. Conclusion: The authors' study indicates that PD-1/PD-L1 inhibitors manifest promising clinical responses in the treatment of CRC with deficient mismatch repair with acceptable treatment-related adverse events.

Efficacy and safety of regorafenib in combination with chemotherapy as second-line therapy in patients with metastatic colorectal cancer: A network meta-analysis.

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 115-115
Author(s):  
Xiaoyu Xie ◽  
Jianwei Zhang ◽  
Huabin Hu ◽  
Yue Cai ◽  
Zehua Wu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Meta Analysis ◽  
Objective Response ◽  
Progression Free Survival ◽  
Biological Agents ◽  
Line Treatment ◽  
Second Line ◽  
Efficacy And Safety ◽  
R Software

115 Background: Recent studies have shown efficacy of chemotherapy (CTX) in combination with different biological agents including regorafenib (REG) in second-line treatment of metastatic colorectal cancer (mCRC). As there is no evidence on the relative efficacy and safety of REG as compared to other biological agents in combination with CTX, we evaluated the same in this network meta-analysis (NMA). Methods: Randomized controlled trials (RCTs) comparing efficacy and safety of biological agents + CTX against CTX alone as second-line treatment of mCRC were retrieved from PubMed, EMBASE and Cochrane databases. Progression free survival (PFS) was the primary outcome, while objective response rate (ORR), overall survival (OS) and safety were secondary outcomes. Outcomes were compared by random/mixed-effects NMA using Bayesian (R software, Gemtc package) and frequentist (R software, netmeta package) approaches. Results: Twelve RCTs comparing 9 different treatment regimens with a total of 6805 patients were included for analysis. Hazard ratios (HR)/ odds ratio (OR)/ relative risk (RR) and 95% confidence intervals (CI) for PFS, ORR and grade> 3 adverse events (AE) of selected comparisons from the results of the NMA are shown in table. Conclusions: REG combined with CTX might be a potential alternative to conventional therapeutic options and could be considered as the best option for treating KRAS and BRAF mutated mCRC patients. Future RCTs are needed to confirm our results. [Table: see text]

Immunotherapy with checkpoint inhibitors in mismatch repair deficient (dMMR) cancers: Looking for a needle in a haystack— But, joy on finding one.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e14073-e14073
Author(s):  
Amit Rauthan ◽  
Poonam Patil ◽  
Tanvi Sood ◽  
Shriniwas Subhash Kulkarni ◽  
Nitin Yashas ◽  
...  
Keyword(s):  
Mismatch Repair ◽  
Solid Tumors ◽  
Checkpoint Inhibitors ◽  
Metastatic Cancer ◽  
Objective Response ◽  
Progression Free Survival ◽  
Skin Toxicity ◽  
Cost Effective ◽  
Limited Data ◽  
Deficient Mismatch Repair

e14073 Background: Pembrolizumab is approved for deficient mismatch repair (dMMR) or high microsatellite instability (MSI-H) metastatic solid tumors with objective response rate (ORR) of 39.6% and response lasting for more than 6 months in 78% patients. Nivolumab is also approved in dMMR metastatic colorectal cancers (mCRC) with ORR of 28% and response lasting greater than 6 months in 67% patients. But finding these patients is difficult as only about 5% of metastatic cancers have dMMR. There is limited data from India in this population. We report our experience with testing and treatment in these patients. Methods: This is a single centre, retrospective study of metastatic solid tumors which had progressed on standard treatment. 137 patients were tested between May 2017 and Dec 2018. MMR testing was done by immunohistochemistry (IHC). The aim was to identify patients with dMMR; and to see their ORR, progression free survival (PFS) at 1 year, and adverse events on treatment with Nivolumab. Results: 137 metastatic cancer patients were tested. 75 had colorectal cancer (mCRC), 30 gastric, 10 hepatobiliary, 10 pancreatic, 8 endometrial, 2 small bowel cancer and 2 had breast cancer. 15 (11%) patients had dMMR. 3 (37%) of endometrium, 5 (16.6%) of stomach, 6 (8%) of mCRC and 1(10%) of hepatobiliary tree cancer had dMMR. 5 of the 15 dMMR patients received immunotherapy with Nivolumab - 2 in mCRC, 2 in stomach and 1 in endometrium. ORR was 60% with 3 partial responses, stable disease was seen in 1 (20%) and progression in 1 (20%). PFS at 1 year was 80%. Treatment was well tolerated.1 patient had hypothyroidism and 1 patient had grade 1 skin toxicity. Conclusions: Testing for dMMR is important in metastatic solid tumors as these patients are ideal for treatment with immunotherapy. But finding dMMR is difficult due to its infrequent presentation, and has been seen in 11% of our unselected patients. We recommend testing for dMMR by IHC in our Indian patients, as this is fast and cost effective. Finding dMMR cancers, and then treating with immunotherapy is rewarding irrespective of the site of origin. High ORR of 60% and 1 year PFS of 80% is very heartening to see in this relapsed metastatic patient group. Treating more dMMR patients and longer followup, will further elucidate the benefit of immunotherapy in our patients.

Efficacy of immunotherapy with PD-1 inhibitor in colorectal cancer: a meta-analysis

2020 ◽  
Vol 9 (18) ◽  
pp. 1285-1292
Author(s):  
Shengqi He ◽  
Dongqing Hu ◽  
Haixia Feng ◽  
Ye Xue ◽  
Jin Jin ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Survival Rate ◽  
Objective Response Rate ◽  
Response Rate ◽  
Meta Analysis ◽  
Objective Response ◽  
Progression Free Survival ◽  
Overall Survival Rate ◽  
Free Survival

Aim: PD-1 inhibitors have a leading role among immunotherapy while its efficacy on colorectal cancer (CRC) patients did not reach consensus and the small sample size remains as a limitation. Therefore, we undertook a meta-analysis on the effects of the monotherapy anti-PD-1 inhibitors in treating metastatic colorectal cancer (mCRC). Materials & methods: We searched databases to identify studies on efficacy of anti-PD-1 inhibitor on CRC. Objectives were objective response rate, progression-free survival rate, disease control rate and overall survival rate with their 95% CI. Results: The overall survival rate at 1-year was 64.2% (95% CI: 0.46–0.83). Disease control rate was 56.5% (CI: 0.27–0.86) and the objective response rate as 19.7% (CI: 0.08–0.32). The 1-year-progression-free survival rate was 38.4% (CI: 0.12–0.66). Sensitivity analysis and subgroup analysis were also conducted. Conclusion: The monotherapy anti-PD-1 inhibitors are effective in treating mCRC and could be a new option for dMMR mCRC patient in first-line treatment.

The prognostic and predictive impact of BRAF mutations in deficient mismatch repair/microsatellite instability-high colorectal cancer: systematic review/meta-analysis

2021 ◽  
Author(s):  
Robin Park ◽  
Laercio Lopes ◽  
Sunggon Lee ◽  
Ivy Riano ◽  
Anwaar Saeed
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Microsatellite Instability ◽  
Mismatch Repair ◽  
Response Rate ◽  
Meta Analysis ◽  
Objective Response ◽  
Wild Type ◽  
Braf Mutations ◽  
Deficient Mismatch Repair

Aims: The authors present a systematic review/meta-analysis of the impact of BRAF mutations on prognosis and immune checkpoint inhibitor (ICI) response in deficient mismatch repair/microsatellite instability-high colorectal cancer. Methods: Hazard ratios for overall survival and odds ratios for objective response rate to ICIs were calculated in BRAF-mutated versus BRAF wild-type patients. Results: After screening, nine and three studies, respectively, were included for analysis of prognosis (analysis A) and ICI response (analysis B). Analysis A showed worse overall survival in BRAF-mutated compared with BRAF wild-type stage I–IV patients (hazard ratio: 1.57; 95% CI: 1.23–1.99), and analysis B showed no difference in objective response rate (odds ratio: 1.04; 95% CI: 0.48–2.25). Conclusion: BRAF mutations are associated with worse overall survival but not differential response to ICIs in deficient mismatch repair/microsatellite instability-high colorectal cancer.

Immune-checkpoint inhibitors versus other systemic therapies in advanced head and neck cancer: a network meta-analysis

Immunotherapy ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 541-555
Author(s):  
Lingrong Tang ◽  
Tingting Liu ◽  
Jun Chen ◽  
Jun Dang ◽  
Guang Li
Keyword(s):  
Head And Neck Cancer ◽  
Head And Neck ◽  
Neck Cancer ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Meta Analysis ◽  
Objective Response ◽  
Progression Free Survival ◽  
Systemic Therapies

Aim: We assessed the efficiency of immune checkpoint inhibitors relative to other systemic therapies in previously treated recurrent/metastatic head and neck cancer. Materials & methods: Relative treatment effects were assessed from eligible randomized controlled trials using Bayesian network meta-analyses. Results: Among 15 trials evaluating 14 treatments, nivolumab achieved the best overall survival (OS) benefit; zalutumumab and buparlisib + paclitaxel provided the best progression-free survival benefit and objective response rate. Buparlisib + paclitaxel and zalutumumab were associated with the best OS rate at 6 and 12 months, respectively; nivolumab yielded the best OS rate at 18–24 months. Conclusion: Nivolumab was the most favorable treatment. Zalutumumab and buparlisib + paclitaxel had better efficiency, and might be a better selection for patients with programmed death-ligand 1-low/negative tumors than other treatments.

scholarly journals Combining Correlated Outcomes and Surrogate Endpoints in a Network Meta-Analysis of Colorectal Cancer Treatments

Cancers ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 2663
Author(s):  
Tung Hoang ◽  
Jeongseon Kim
Keyword(s):  
Colorectal Cancer ◽  
Meta Analysis ◽  
Progression Free Survival ◽  
Efficacy And Safety ◽  
Cancer Treatments ◽  
Free Survival ◽  
Hazard Ratios ◽  
Credible Intervals ◽  
Grade 3 ◽  
Selection Of

This study aimed to investigate the efficacy and safety of systemic therapies in the treatment of unresectable advanced or metastatic colorectal cancer. Predicted hazard ratios (HRs) and their 95% credible intervals (CrIs) for overall survival (OS) were calculated from the odds ratio (OR) for the overall response rate and/or HR for progression-free survival using multivariate random effects (MVRE) models. We performed a network meta-analysis (NMA) of 49 articles to compare the efficacy and safety of FOLFOX/FOLFIRI±bevacizumab (Bmab)/cetuximab (Cmab)/panitumumab (Pmab), and FOLFOXIRI/CAPEOX±Bmab. The NMA showed significant OS improvement with FOLFOX, FOLFOX+Cmab, and FOLFIRI+Cmab compared with that of FOLFIRI (HR = 0.84, 95% CrI = 0.73–0.98; HR = 0.76, 95% CrI = 0.62–0.94; HR = 0.80, 95% CrI = 0.66–0.96, respectively), as well as with FOLFOX+Cmab and FOLFIRI+Cmab compared with that of FOLFOXIRI (HR = 0.69, 95% CrI = 0.51–0.94 and HR = 0.73, 95% CrI = 0.54–0.97, respectively). The odds of adverse events grade ≥3 were significantly higher for FOLFOX+Cmab vs. FOLFIRI+Bmab (OR = 2.34, 95% CrI = 1.01–4.66). Higher odds of events were observed for FOLFIRI+Pmab in comparison with FOLFIRI (OR = 2.16, 95% CrI = 1.09–3.84) and FOLFIRI+Bmab (OR = 3.14, 95% CrI = 1.51–5.89). FOLFOX+Cmab and FOLFIRI+Bmab showed high probabilities of being first- and second-line treatments in terms of the efficacy and safety, respectively. The findings of the efficacy and safety comparisons may support the selection of appropriate treatments in clinical practice. PROSPERO registration: CRD42020153640.

scholarly journals Efficacy and safety of regorafenib as beyond second-line therapy in patients with metastatic colorectal cancer: an adjusted indirect meta-analysis and systematic review

2020 ◽  
Vol 12 ◽  
pp. 175883592094093
Author(s):  
Yinying Wu ◽  
Yangwei Fan ◽  
Danfeng Dong ◽  
Xuyuan Dong ◽  
Yuan Hu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Meta Analysis ◽  
Objective Response ◽  
Cochrane Library ◽  
Second Line ◽  
Efficacy And Safety ◽  
Line Therapy ◽  
Third Line Therapy ◽  
Third Line

Background: The evidence base for optimum third-line therapy for metastatic colorectal cancer (mCRC) is not conclusive. Recent studies have demonstrated the efficacy of regorafenib as third-line therapy in mCRC. This indirect meta-analysis compared the efficacy and safety of regorafenib with other available third-line therapies for mCRC. Methods: A literature search for randomized controlled trials (RCTs) was conducted in PubMed, Embase, and Cochrane Library for studies evaluating the efficacy and safety of fruquintinib, regorafenib, TAS-102, and nintedanib as third-line therapies in patients with mCRC. Overall survival (OS) and progression-free survival (PFS) were the primary outcomes, while objective response rate (ORR) and safety were the secondary outcomes. Hazard ratio (HR) and relative risk (RR) with their respective 95% confidence interval (CI) were used for analysis of survival, clinical response, and safety data. An adjusted indirect meta-analysis with placebo as the common comparator was performed. Results: We identified eight RCTs comparing regorafenib (two studies), fruquintinib (two studies), TAS-102 (three studies), and nintedanib (one study) against placebo. The OS with regorafenib was significantly better when compared with nintedanib (HR = 0.66; 95% CI: 0.45, 0.95, p = 0.02) but was similar to that of fruquintinib (HR = 1.01; 95% CI: 0.67, 1.52, p = 0.94) and TAS-102 (HR = 0.97; 95% CI: 0.68, 1.38, p = 0.88). The PFS and ORR for regorafenib were slightly better than those of TAS-102 (PFS: HR = 0.86, 95% CI: 0.54, 1.37, p = 0.5; ORR: RR = 1.13, 95% CI: 0.11, 11.05, p = 0.92) and nintedanib (PFS: HR = 0.68, 95% CI: 0.42, 1.10, p = 0.12; ORR: not reported) but were lower than those for fruquintinib (PFS: HR = 1.53, 95% CI: 0.93, 2.52, p = 0.08; ORR: RR = 0.68269, 95% CI: 0.045, 10.32, p = 0.79). Safety analysis showed that the RR of adverse events (AEs) was lesser in patients treated with regorafenib in comparison with that in patients treated with fruquintinib, but was similar to that in patients treated with nintedanib and TAS-102. Conclusion: Regorafenib has efficacy similar to that of TAS-102 and better safety when compared with fruquintinib. Considering the mechanism of action of regorafenib, which targets multiple factors in the angiogenic pathway, it could be an ideal option for treatment in the beyond second-line setting.

scholarly journals A meta-analysis comparing regorafenib with TAS-102 for treating refractory metastatic colorectal cancer

2020 ◽  
Vol 48 (7) ◽  
pp. 030006052092640
Author(s):  
Guan-Li Su ◽  
Yuan-Yuan Wang ◽  
Jin-Cheng Wang ◽  
Hao Liu
Keyword(s):  
Colorectal Cancer ◽  
Adverse Events ◽  
Metastatic Colorectal Cancer ◽  
Odds Ratio ◽  
Meta Analysis ◽  
Progression Free Survival ◽  
Similar Efficacy ◽  
Efficacy And Safety ◽  
Free Survival ◽  
Hand Foot Syndrome

Objective We performed this meta-analysis to compare the efficacy and toxicity of regorafenib and TAS-102. Methods Electronic databases were searched to identify studies comparing the efficacy and safety of regorafenib and TAS-102 in patients with chemotherapy-refractory metastatic colorectal cancer using pooled analyses. Results Three clinical trials were included in this analysis. Regarding the reasons for treatment discontinuation, regorafenib was significantly associated with disease progression (odds ratio [OR] = 0.33, 95% confidence interval [CI] = 0.21–0.50) and adverse events (OR = 4.38, 95% CI = 2.69–7.13). However, overall (OR = 0.97, 95% CI = 0.81–1.17) and progression-free survival (OR = 1.01, 95% CI = 0.86–1.18) did not significantly differ between the groups. The most common treatment-related adverse events in the regorafenib group were neutropenia (OR = 0.06, 95% CI = 0.03–0.11), hand–foot syndrome (OR = 50.34, 95% CI = 10.44–242.84), and liver dysfunction (OR = 34.51, 95% CI = 8.30–143.43). Conversely, the incidence of thrombocytopenia did not differ between the two groups. Conclusions Regorafenib and TAS-102 have similar efficacy but different adverse event profiles. Differences in the toxicity profiles of the two drugs will help guide treatment selection.

The efficacy and safety of CapeOX plus bevacizumab therapy with a planned oxaliplatin stop-and-go strategy in patients with metastatic colorectal cancer: A multi-center, single-arm, phase II study (CCOG-0902 study).

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 795-795
Author(s):  
Yuuki Sunakawa ◽  
Goro Nakayama ◽  
Kiyoshi Ishigure ◽  
Hiroyuki Yokoyama ◽  
Keisuke Uehara ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Maintenance Therapy ◽  
Metastatic Colorectal Cancer ◽  
Objective Response ◽  
Sensory Neuropathy ◽  
Progression Free Survival ◽  
Japanese Patients ◽  
Efficacy And Safety ◽  
Stop And Go ◽  
Grade 3

795 Background: The aim of this study was to evaluate the efficacy and safety of CapeOX plus bevacizumab with a planned oxaliplatin stop-and-go strategy in Japanese patients with metastatic colorectal cancer (mCRC). Methods: Patients with untreated mCRC were treated with 4 cycles of CapeOX plus bevacizumab therapy, followed by capecitabine plus bevacizumab maintenance therapy. Reintroduction of oxaliplatin was scheduled after 8 cycles of maintenance therapy or upon tumor progression. The primary endpoint was progression-free survival (PFS), and secondary end points included overall survival (OS), objective response rate to each treatment, reintroduction rate of oxaliplatin, frequency of peripheral sensory neuropathy (PSN), and safety. Results: The 52 patients who received the protocol treatment were included in the evaluation of efficacy and safety. Median PFS and OS were 12.4 months (95% confidence interval [CI], 10.0–14.8) and 30.6 months (95% CI, 27.6–33.5), respectively. The objective response rates were 55.8% for the initial CapeOX plus bevacizumab therapy, 17.8% for capecitabine plus bevacizumab maintenance therapy, and 31.0% for reintroduced CapeOX plus bevacizumab therapy. The frequency of PSN was 63.5%, including 3.8% of patients with grade 3 PSN. No patients required treatment discontinuation because of PSN during the induction or maintenance therapy. Conclusions: CapeOX plus bevacizumab therapy with a planned oxaliplatin stop-and-go strategy is a feasible first-line treatment for Japanese patients with mCRC. Clinical trial information: UMIN000006478.

scholarly journals Current Systemic Treatment Options in Metastatic Urothelial Carcinoma after Progression on Checkpoint Inhibition Therapy—A Systemic Review Combined with Single-Group Meta-Analysis of Three Studies Testing Enfortumab Vedotin

Cancers ◽  
2021 ◽  
Vol 13 (13) ◽  
pp. 3206
Author(s):  
Susanne Deininger ◽  
Peter Törzsök ◽  
David Oswald ◽  
Lukas Lusuardi
Keyword(s):  
Urothelial Carcinoma ◽  
Checkpoint Inhibitors ◽  
Meta Analysis ◽  
Treatment Options ◽  
Objective Response ◽  
Progression Free Survival ◽  
Current Treatment ◽  
Systemic Review ◽  
Single Group ◽  
Metastatic Urothelial Carcinoma

Background: In the first and second-line therapy of metastatic urothelial carcinoma (mUC), checkpoint inhibitors (CPI) such as Pembrolizumab and Atezolizumab have been widely implemented. Little is currently known about what therapeutic options are effective after therapy with CPI. This article presents a systemic review of current treatment options in this setting. Methods: From August 2020 to 15 April 2021, a literature search was performed through the PubMed/Medline. Subsequently, a single-group meta-analysis of three studies testing Enfortumab vedotin (EV) was conducted. Results: Five therapy regimens tested in the post-CPI setting with adequate data were identified: Chemotherapy (CT), Ramucirumab plus Docetaxel, Erdafitinib (Erd), EV, and Sacituzumab govitecan (SG). In n = 74 + 125 + 288 patients, the single-group meta-analysis showed an objective response rate of 42.1% for EV compared to 17.9% for CT in a similar setting. EV was also ahead in progression free survival (5.9 months with EV vs. 3.7 months with CT) and overall survival (12.8 months with EV vs. 9.0 months with CT). Conclusion: Most data are currently available for EV. Further research is needed on the question of which patients’ subcollectives particularly benefit from which therapeutic approach.

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