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Efficacy of PD-1 Inhibitors With nCRT in LARC

June, 06, 2024 | Colorectal Cancer, Gastrointestinal Cancer

KEY TAKEAWAYS

  • The study aimed to investigate the efficacy and safety of PD-1/PD-L1 inhibitors combined with nCRT in treating pts with microsatellite-stable LARC.
  • Researchers noticed that PD-1/PD-L1 inhibitors combined with nCRT resulted in promising response rates and manageable toxicity.

Several studies have explored the effectiveness of PD-1/PD-L1 inhibitors combined with neoadjuvant chemoradiotherapy (nCRT) in the treatment of locally advanced rectal cancer (LARC), particularly in patients with microsatellite stable (MSS) or mismatch repair proficient (pMMR) LARC.

Lei Yang and the team undertook a single-arm systematic review to comprehensively evaluate the advantages and potential risks associated with the use of PD-1/PD-L1 inhibitors in conjunction with nCRT for patients diagnosed with LARC.

They performed an inclusive analysis by searching PubMed, Embase, Cochrane Library, ClinicalTrials.gov, ASCO, and ESMO for related studies. The main outcomes evaluated were pathologic complete response (pCR), major pathological response (MPR), anal preservation, and adverse effects (AEs).

About 14 articles, including 533 patients with LARC, were analyzed. The pooled pCR, MPR, and anal preservation rates were 36%, 66%, and 86%. Grade ≥3 AE’s occurred in 20%. Subgroup analysis showed that dMMR/MSI-H had a pooled pCR of 100% and MPR of 100%, while pMMR/MSS had a pooled pCR of 38% and MPR of 60%.

Short-course radiotherapy and long-course radiotherapy pooled pCR rates of 51% and 30%, respectively. The rates of pCR for the concurrent and sequential immuno-chemoradiotherapy subgroups were 30% and 40%, respectively, mirroring pCR rates for the PD-L1 and PD-1 inhibitor subgroups at 32% and 40%, respectively.

The study concluded that in LARC cases, PD-1/PD-L1 inhibitors combined with nCRT have shown promising response rates and acceptable toxicity profiles. This combination therapy has demonstrated positive outcomes even in patients with MSS LARC.

The study was funded by the Natural Science Foundation of Hebei Province (H2020206311), the Central Guiding Local Science and Technology Development Fund Project (Hebei Science and Technology Department Project) (226Z7712G), and the government-funded Clinical Medicine Excellent Talents Project of Hebei Provincial Department of Finance (2022-180).

Source: https://pubmed.ncbi.nlm.nih.gov/38846948/

Yang L, Cui X, Wu F, et al. (2024). “The efficacy and safety of neoadjuvant chemoradiotherapy combined with immunotherapy for locally advanced rectal cancer patients: a systematic review.” Front Immunol. 2024 May 15;15:1392499. doi: 10.3389/fimmu.2024.1392499. PMID: 38846948; PMCID: PMC11154111.

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