Pembrolizumab versus bevacizumab plus modified FOLFOX6 in metastatic MSI-H/dMMR colorectal cancer: a multicenter retrospective study with CT evaluation

Frontiers in Oncology, Год журнала: 2025, Номер 15

Опубликована: Апрель 4, 2025

Objective The optimal therapeutic strategy for metastatic microsatellite instability-high/mismatch repair-deficient (MSI-H/dMMR) colorectal cancer (CRC) remains uncertain. This multicenter retrospective study compared the efficacy and safety of pembrolizumab monotherapy versus bevacizumab combined with modified FOLFOX6 (mFOLFOX6) in this molecularly defined population. Methods Consecutive patients MSI-H/dMMR CRC treated or plus mFOLFOX6 at two tertiary centers (2017–2024) were analyzed. Dual primary endpoints included overall survival (OS) progression-free (PFS); secondary encompassed incidence grade ≥3 treatment-emergent adverse events (AEs). Results Among 58 eligible (PE: n=30; BF: n=28), PE cohort demonstrated a significantly higher objective response rate (ORR) to BF (XX% vs XX%, p=0.030) after median follow-up 18.0 months (IQR: 1.0–24.0). Survival analyses revealed superior outcomes cohort, OS 12.0 (95% CI: 10.2–14.1) 8.8 7.1–9.6) (HR=0.55, 95% 0.29–0.56; p=0.02). Similarly, PFS was prolonged (7.0 months, 5.3–9.3) relative (3.7 2.2–5.4; HR=0.46, 0.24–0.89; p<0.001). No statistically significant intergroup differences observed AE rates. Conclusion Pembrolizumab improved over bevacizumab-based chemotherapy CRC, manageable profile. These results reinforce PD-1 inhibitors as first-line therapy population, while highlighting tumor mutation burden (TMB) critical biomarkers personalized strategies.

Язык: Английский

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Inflammation, Immunosuppression, and Immunotherapy in Pancreatic Cancer—Where Are We Now?

Cancers, Год журнала: 2025, Номер 17(9), С. 1484 - 1484

Опубликована: Апрель 28, 2025

Pancreatic cancer (PC) is one of the most commonly diagnosed and deadliest neoplasms in modern world. Over past few years, incidence PC has risen with only a slight improvement overall survival. Moreover, survival primarily driven by diagnoses localized stage disease, rather than new treatment methods. The inflammatory process key mediator development, yet also immune-resistant tumors. Patients rarely benefit from monotherapy immune checkpoint inhibitors; nevertheless, latest biological findings on complexity pancreatic tumor microenvironment might be translated into designing clinical studies that combine various approaches to overcome single-agent immunotherapy resistance. On other hand, focusing inflammation may lead development inflammation-based prognostic markers for patients. This review aims describe current state knowledge regarding complex relationships between systemic local inflammation, response, immunosuppression, therapeutic options PC.

Язык: Английский

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Non-operative management after immune checkpoint inhibitors for early-stage, dMMR/MSI-H gastrointestinal cancers

Cancer Treatment Reviews, Год журнала: 2024, Номер 128, С. 102752 - 102752

Опубликована: Май 12, 2024

Язык: Английский

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

Cancers, Год журнала: 2023, Номер 15(11), С. 2893 - 2893

Опубликована: Май 24, 2023

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

Язык: Английский

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Conversion therapy with pembrolizumab for a peritoneal metastasis of rectal cancer causing hydronephrosis in a patient with Lynch syndrome

Clinical Journal of Gastroenterology, Год журнала: 2024, Номер 17(3), С. 451 - 456

Опубликована: Фев. 23, 2024

Язык: Английский

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