Pembrolizumab for previously treated, microsatellite instability–high/mismatch repair–deficient advanced colorectal cancer: final analysis of KEYNOTE-164

Le, Dung T.; Díaz, Luis A.; Kim, Tae Won; Cutsem, Éric Van; Jäger, Dirk; Burge, Matthew; O’Neil, Bert H.; Kavan, Petr; Yoshino, Takayuki; Guimbaud, Rosine; Taniguchi, Hiroya; Élez, Elena; Al-Batran, Salah-Eddin; Boland, Patrick M.; Cui, Yi; Leconte, Pierre; Marinello, Patricia; Thewis, André

doi:10.1016/j.ejca.2023.02.016

Cited by 22 publications

(16 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Instead, our data implied that even in the population that exhibited the NRAS or BRAF mutation, bevacizumab as a first‐line targeted therapy did not offer greater survival benefits over anti‐EGFR mAb. Immunotherapy was proven to be beneficial for microsatellite instability‐high colorectal cancer in multiple clinical trials, 36–38 but the enrollment period of our study was before the publication of these results. Many genetic alterations were found to be predictive of the efficacy of specific therapies, such as HER2 amplification and tumor mutation burden 39 .…”

Section: Discussionmentioning

confidence: 99%

Treatment outcome comparisons of first‐line targeted therapy in patients with KRAS wild‐type metastatic colorectal cancer: A nationwide database study

2023

View full text Add to dashboard Cite

BackgroundThe first‐line systemic therapy for metastatic colorectal cancer (mCRC) is a combination of one targeted therapy agent and a chemotherapy doublet. Whether bevacizumab or anti‐epidermal growth factor receptor (anti‐EGFR) monoclonal antibody (mAb) is the more effective addition to a chemotherapy doublet as the first‐line treatment for inoperable KRAS wild‐type mCRC remains controversial in prior clinical trials. Moreover, the association between the sidedness of primary tumors and the efficacy of anti‐EGFR mAb needs to be addressed.MethodsWe established a cohort of patients with KRAS wild‐type mCRC who were treated with first‐line targeted therapy plus doublet chemotherapy between 2013 and 2018 using Taiwan's National Health Insurance Research Database. Secondary surgery was defined as either resection of primary tumors, liver metastases, lung metastases, or radiofrequency ablation.ResultsA total of 6482 patients were included; bevacizumab and anti‐EGFR mAb were the first‐line targeted therapies in 3334 (51.4%) and 3148 (48.6%) patients, respectively. Compared with those who received bevacizumab, patients who received anti‐EGFR mAb exhibited significantly longer overall survival (OS; median, 23.1 vs. 20.2 months, p = 0.012) and time to treatment failure (TTF; median, 11.3 vs. 10 months, p < 0.001). Among left‐sided primary tumors, the OS and TTF benefits of anti‐EGFR mAb remained. Among right‐sided primary tumors, the OS and TTF were similar regardless of the type of targeted therapy. In multivariate analyses, first‐line anti‐EGFR mAb therapy remained an independent predictor of longer OS and TTF for left‐sided primary tumors. Patients who received anti‐EGFR mAb were more likely to receive secondary surgery (29.6% vs. 22.6%, p < 0.0001) than patients who received bevacizumab.ConclusionFor patients who received first‐line doublet chemotherapy for KRAS wild‐type mCRC, adding anti‐EGFR mAb was associated with significantly longer OS and TTF, especially for left‐sided primary tumors.

show abstract

Section: Discussionmentioning

confidence: 99%

Treatment outcome comparisons of first‐line targeted therapy in patients with KRAS wild‐type metastatic colorectal cancer: A nationwide database study

2023

View full text Add to dashboard Cite

show abstract

“…As a result, errors in DNA replication accumulate, leading to an increased mutational load in the tumor cells. This phenomenon is particularly relevant in the context of colorectal cancer, where dMMR is seen in approximately 15% of cases. , …”

Section: Molecular Profiling Of Colorectal Cancermentioning

confidence: 99%

“…This phenomenon is particularly relevant in the context of colorectal cancer, where dMMR is seen in approximately 15% of cases. 37,38 The presence of MSI and dMMR in colorectal cancer has several important clinical implications. First, it is associated with a more favorable prognosis.…”

Section: Molecular Profiling Of Colorectal Cancermentioning

confidence: 99%

“…These therapies harness the body’s immune system to attack cancer cells, exploiting the higher mutational burden in MSI-high tumors. The approval of pembrolizumab, a PD-1 inhibitor, for the treatment of dMMR or MSI-high colorectal cancer has provided a ground-breaking option for patients with these molecular features. , …”

Section: Molecular Profiling Of Colorectal Cancermentioning

confidence: 99%

See 1 more Smart Citation

Advances in Precision Medicine Approaches for Colorectal Cancer: From Molecular Profiling to Targeted Therapies

Kiran,

Yashaswini,

Maheshwari

et al. 2024

ACS Pharmacol. Transl. Sci.

View full text Add to dashboard Cite

Precision medicine is transforming colorectal cancer treatment through the integration of advanced technologies and biomarkers, enhancing personalized and effective disease management. Identification of key driver mutations and molecular profiling have deepened our comprehension of the genetic alterations in colorectal cancer, facilitating targeted therapy and immunotherapy selection. Biomarkers such as microsatellite instability (MSI) and DNA mismatch repair deficiency (dMMR) guide treatment decisions, opening avenues for immunotherapy. Emerging technologies such as liquid biopsies, artificial intelligence, and machine learning promise to revolutionize early detection, monitoring, and treatment selection in precision medicine. Despite these advancements, ethical and regulatory challenges, including equitable access and data privacy, emphasize the importance of responsible implementation. The dynamic nature of colorectal cancer, with its tumor heterogeneity and clonal evolution, underscores the necessity for adaptive and personalized treatment strategies. The future of precision medicine in colorectal cancer lies in its potential to enhance patient care, clinical outcomes, and our understanding of this intricate disease, marked by ongoing evolution in the field. The current reviews focus on providing in-depth knowledge on the various and diverse approaches utilized for precision medicine against colorectal cancer, at both molecular and biochemical levels.

show abstract

“…Food and Drug Administration approvals of immunotherapeutic drugs for mCRC are the result of different clinical trials, such as KEYNOTE-164, KEYNOTE-177 and CheckMate-142. The first two explored the functionality and safety of pembrolizumab (anti-PD-1), while the third examined nivolumab (anti-PD-1) plus ipilimumab (anti-CTLA4) [63][64][65][66][67]. KEYNOTE-164 was an international phase II multicenter study that enrolled a total of 124 patients with locally advanced or metastatic MSI-H and/or dMMR CRC.…”

Section: Ilc3s Microbiota and Crc Immunotherapy 41 Colon Cancer And R...mentioning

confidence: 99%

Crosstalk between ILC3s and Microbiota: Implications for Colon Cancer Development and Treatment with Immune Check Point Inhibitors

Drommi,

Calabrò,

Vento

et al. 2023

Cancers

View full text Add to dashboard Cite

Type 3 innate lymphoid cells (ILC3s) are primarily tissue-resident cells strategically localized at the intestinal barrier that exhibit the fast-acting responsiveness of classic innate immune cells. Populations of these lymphocytes depend on the transcription factor RAR-related orphan receptor and play a key role in maintaining intestinal homeostasis, keeping host–microbial mutualism in check. Current evidence has indicated a bidirectional relationship between microbiota and ILC3s. While ILC3 function and maintenance in the gut are influenced by commensal microbiota, ILC3s themselves can control immune responses to intestinal microbiota by providing host defense against extracellular bacteria, helping to maintain a diverse microbiota and inducing immune tolerance for commensal bacteria. Thus, ILC3s have been linked to host–microbiota interactions and the loss of their normal activity promotes dysbiosis, chronic inflammation and colon cancer. Furthermore, recent evidence has suggested that a healthy dialog between ILC3s and gut microbes is necessary to support antitumor immunity and response to immune checkpoint inhibitor (ICI) therapy. In this review, we summarize the functional interactions occurring between microbiota and ILC3s in homeostasis, providing an overview of the molecular mechanisms orchestrating these interactions. We focus on how alterations in this interplay promote gut inflammation, colorectal cancer and resistance to therapies with immune check point inhibitors.

show abstract

Pembrolizumab for previously treated, microsatellite instability–high/mismatch repair–deficient advanced colorectal cancer: final analysis of KEYNOTE-164

Cited by 22 publications

References 30 publications

Treatment outcome comparisons of first‐line targeted therapy in patients with KRAS wild‐type metastatic colorectal cancer: A nationwide database study

Treatment outcome comparisons of first‐line targeted therapy in patients with KRAS wild‐type metastatic colorectal cancer: A nationwide database study

Advances in Precision Medicine Approaches for Colorectal Cancer: From Molecular Profiling to Targeted Therapies

Crosstalk between ILC3s and Microbiota: Implications for Colon Cancer Development and Treatment with Immune Check Point Inhibitors

Contact Info

Product

Resources

About