The Efficacy and Safety of Regorafenib in Combination With Anti-PD-1 Antibody in Refractory Microsatellite Stable Metastatic Colorectal Cancer: A Retrospective Study

Li, Jisheng; Liu, Cong; Liu, Jintao; Peng, Ling; Wang, Jun; Feng, Alei; Yue, Jinbo; Li, Li; Wang, Xiuwen; Wang, Xiangling

doi:10.3389/fonc.2020.594125

Cited by 27 publications

(29 citation statements)

References 33 publications

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Section: Immune Checkpoint Inhibitors Therapysupporting

confidence: 92%

“…In a retrospective study of 23 MSS or pMMR mCRC treated with regorafenib plus antiPD-1 antibody, ORR was 0% and DCR was 78.3% (18/23), with the median PFS of 3.1 months (95% CI, 2.32-3.89). The results are consistent with clinical trials above(48). In another retrospective study, Wang et al found that MSS CRC patients with no history of liver metastasis are more likely to benefit from this combination regorafenib plus antiPD-1 antibody(49).…”

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confidence: 79%

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Perspectives on Immunotherapy of Metastatic Colorectal Cancer

et al. 2021

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Colorectal cancer, especially liver metastasis, is still a challenge worldwide. Traditional treatment such as surgery, chemotherapy and radiotherapy have been difficult to be further advanced. We need to develop new treatment methods to further improve the poor prognosis of these patients. The emergence of immunotherapy has brought light to mCRC patients, especially those with dMMR. Based on several large trials, some drugs (pembrolizumab, nivolumab) have been approved by US Food and Drug Administration to treat the patients diagnosed with dMMR tumors. However, immunotherapy has reached a bottleneck for other MSS tumors, with low response rate and poor PFS and OS. Therefore, more clinical trials are underway toward mCRC patients, especially those with MSS. This review is intended to summarize the existing clinical trials to illustrate the development of immunotherapy in mCRC patients, and to provide a new thinking for the direction and experimental design of immunotherapy in the future.

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Section: Immune Checkpoint Inhibitors Therapysupporting

confidence: 92%

supporting

confidence: 79%

Perspectives on Immunotherapy of Metastatic Colorectal Cancer

et al. 2021

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“…However, a retrospective study of 18 MSS CRC patients at the American Cancer Center in 2019 failed to reveal the comparable clinical activity of regorafenib plus nivolumab, with a median PFS of 2.0 months (30). In a retrospective study, 23 Asian patients with MSS or pMMR mCRC treated with regorafenib combined with anti-PD-1 antibody had an ORR of 0% and a median PFS of 3.1 months (31). In our study, 23 MSS mCRC patients treated with regorafenib combined with PD-1 inhibitors had an ORR of 8.7% and a median PFS of 3.9 months, similar to those in the Asian population.…”

Section: Discussionmentioning

confidence: 99%

“…However, a retrospective study of 18 patients at the American Cancer Center failed to reveal comparable clinical activity of regorafenib plus nivolumab (30). In a retrospective clinical study of regorafenib combined with anti-PD-1 antibody in the treatment of MSS or pMMR mCRC patients in China, some potential benefits in disease control rate (DCR) and PFS were observed, albeit the results showed no objective effect (31). Therefore, additional evidence is needed to evaluate this joint strategy.…”

Section: Introductionmentioning

confidence: 99%

Efficacy and Safety of Fruquintinib Plus PD-1 Inhibitors Versus Regorafenib Plus PD-1 Inhibitors in Refractory Microsatellite Stable Metastatic Colorectal Cancer

Sun

Huang

et al. 2021

Front. Oncol.

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BackgroundMicrosatellite stability (MSS) or mismatch repair proficient (pMMR) metastatic colorectal cancer (mCRC) is resistant to immune checkpoint inhibitors. Studies have shown that antiangiogenic drugs combined with programmed death receptor-1 (PD-1) inhibitors can improve immunosuppression. The purpose of this study was to compare the efficacy of fruquintinib combined with PD-1 inhibitor (FP) and regorafenib combined with PD-1 inhibitor (RP) in the treatment of advanced mCRC with MSS or pMMR.Materials and MethodsWe retrospectively collected advanced MSS or pMMR mCRC patient data from The Second Affiliated Hospital of Nanchang, China, from June 2019 to March 2021. Then, we analyzed and compared the efficacy and safety of FP and RP.ResultsA total of 51 patients who met the criteria were divided into FP (n = 28) and RP groups (n = 23). The overall response rate of the FP and RP groups was 7.1% and 8.7% and the disease control rate was 89.3% and 56.5%, respectively. The median progression-free survival (PFS) time was higher in the FP group than in the RP group (6.4 vs. 3.9 months, respectively; P = 0.0209). Patients with no liver metastasis, KRAS wild type, and left colon tumor may benefit from FP. Eight patients (15.7%) had grade 3 toxicity related to treatment. Cox multivariate regression analysis showed that the treatment method was an independent risk factor for median PFS time.ConclusionOur study indicates that FP could improve PFS time of patients with advanced mCRC compared with RP.

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“…The most common immune checkpoint inhibitors in use and their molecular target are summarised in Table 1 . A summary of prospective trials of immune checkpoint inhibitors is shown in Table 2 [ 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 ].…”

Section: Colorectal Cancer and The Tumour Microenvironment—an Immunological Basis For Targeted Therapymentioning

confidence: 99%

Targeting Metastatic Colorectal Cancer with Immune Oncological Therapies

Galbraith

Wood

Steele

2021

Cancers

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Metastatic colorectal cancer carries poor prognosis, and current therapeutic regimes convey limited improvements in survival and high rates of detrimental side effects in patients that may not stand to benefit. Immunotherapy has revolutionised cancer treatment by restoring antitumoural mechanisms. However, the efficacy in metastatic colorectal cancer, is limited. A literature search was performed using Pubmed (Medline), Web of Knowledge, and Embase. Search terms included combinations of immunotherapy and metastatic colorectal cancer, primarily focusing on clinical trials in humans. Analysis of these studies included status of MMR/MSS, presence of combination strategies, and disease control rate and median overall survival. Evidence shows that immune checkpoint inhibitors, such as anti-PD1 and anti-PD-L1, show efficacy in less than 10% of patients with microsatellite stable, MMR proficient colorectal cancer. In the small subset of patients with microsatellite unstable, MMR deficient cancers, response rates were 40–50%. Combination strategies with immunotherapy are under investigation but have not yet restored antitumoural mechanisms to permit durable disease regression. Immunotherapy provides the potential to offer additional strategies to established chemotherapeutic regimes in metastatic colorectal cancer. Further research needs to establish which adjuncts to immune checkpoint inhibition can unpick resistance, and better predict which patients are likely to respond to individualised therapies to not just improve response rates but to temper unwarranted side effects.

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The Efficacy and Safety of Regorafenib in Combination With Anti-PD-1 Antibody in Refractory Microsatellite Stable Metastatic Colorectal Cancer: A Retrospective Study

Cited by 27 publications

References 33 publications

Perspectives on Immunotherapy of Metastatic Colorectal Cancer

Perspectives on Immunotherapy of Metastatic Colorectal Cancer

Efficacy and Safety of Fruquintinib Plus PD-1 Inhibitors Versus Regorafenib Plus PD-1 Inhibitors in Refractory Microsatellite Stable Metastatic Colorectal Cancer

Targeting Metastatic Colorectal Cancer with Immune Oncological Therapies

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