MSI-H/dMMR

Individual patient data (IPD) from the KEYNOTE-177 and CheckMate-8HW trials were collected with IPDfromKM and used to develop a Markov model with a 30-year duration and three mutually exclusive health states, providing a framework for the evaluation of the cost-effectiveness of first-line nivolumab together with ipilimumab, pembrolizumab, and chemotherapy for treating MSI-H/dMMR advanced CRC. In addition, the established model is stable. First-line immunotherapeutic treatments for MSI-H/dMMR advanced CRC cases in the USA appears to be cost-effective, with a dual-immunotherapeutic regimen consisting of nivolumab plus ipilimumab being preferable.

shows a cCR rate of 100% that allowed sparing chemoradiation and surgery to all included patients. Here, we present three clinical cases of patients with dMMR and MSI-H LARC treated with neoadjuvant dostarlimab at three Italian institutions with radiological evidence of disease progression while on treatment and discuss potential similarities among them to understand when and how this apparently rare event may occur.

The safety profile was well tolerated. ClinicalTrials.gov identifier: NCT03852823.

While the biological and molecular determinants underlying the response rates observed in the NICHE-2 trial remain to be fully elucidated, the work by Tan et al. suggests that biomarker-guided neoadjuvant immunotherapy could represent a valuable strategy to achieve pathological responses in early-stage pMMR CC, despite its clinical relevance requiring further evaluation.

We report promising downstaging and pCR/cCR rate of ICI for initially-unresectable MMRd CRC. ICI-first can permit curative resection, with risk of local complication from significant treatment response. Larger, multi-centre studies are needed to validate these findings.

Early use of anti-PD-(L)1 therapy is associated with prolonged disease control and may be linked to enhanced responsiveness to subsequent therapies, mostly based on NSCLC data. Additionally, EFS2/PRFS2/PFS2 are solid candidate surrogates for OS and could be considered for routine inclusion and prespecified into immunotherapy RCTs to better capture long-term benefit and inform regulatory, clinical, and reimbursement decision-making.

HER2 2 + /3 + immunoreactivity was detected in 16.7 % of advanced non-p53abn EC, particularly enriched in CCC. These findings highlight the potential clinical significance of HER2 testing in non-p53abn patients.

These data highlight the importance of dMMR testing in patients with advanced solid tumors in China to optimize biomarker testing and treatment decisions.

After 5 months, the treatment is ongoing. This illustrates that pembrolizumab can have an effect in some patients with prostate cancer and underscores the importance of molecular diagnostics.

Consequently, the patient was diagnosed with pancreatic medullary carcinoma. To our knowledge, only 33 cases of pancreatic medullary carcinoma have been reported to date, and this is the first report to describe its cytological features.

It demonstrates that targeting these lesions can yield outcomes that meet or exceed the benchmarks set by the NAPOLI-1 trial (liposomal irinotecan plus 5-fluorouracil and leucovorin), with a median overall survival of 6.2 months and progression-free survival of 3.1 months. Objective response rates reach 33% with adagrasib in KRAS G12C PDAC, 22% with olaparib maintenance in germline BRCA1/2 cancers, and over 50% with RET or NTRK inhibitors with fusion alterations; pembrolizumab produces durable benefit in the 1-3% of tumours that are MSI-H/dMMR. Emerging data highlight NRG1 fusions (overall response rate 42% with zenocutuzumab), HER2 amplification, MTAP deletion with PRMT5 dependency and variant-specific (MRTX1133) or pan-RAS (daraxonrasib) inhibitors as the next frontier...Taken together, these advances represent a substantive therapeutic progress in PDAC over the past decades, even though they currently apply to a minority of patients. These findings underscore the necessity of comprehensive next-generation sequencing for every patient with advanced disease, enabling identification of rare, yet clinically meaningful, targets and moving PDAC management towards a precision-oncology paradigm.

MSS/EMAST-L tumors aligned with chromosomally stable, KRAS/Wnt-driven CRC. In conclusion, MSS/EMAST-H tumors represent an underrecognized CRC subtype with intermediate genomic instability and a distinctive molecular profile, with potential implications for prognostic assessment and personalized therapeutic strategies.