Pembrolizumab is a PD-1 checkpoint inhibitor and neoadjuvant immunotherapy agent that blocks the pd 1 axis, with benefit also linked to pd l1-positive disease in resectable locally advanced head and neck squamous cell carcinoma. It is used across multiple solid tumors, including cervical cancer, colorectal cancer, head and neck squamous cell carcinoma, her2 negative gastric cancer, melanoma, and triple negative breast cancer, and is an FDA-approved first-line option in head and neck squamous cell carcinoma. A key biomarker is mismatch-repair status: the literature describes it as a critical predictor of immune checkpoint inhibitor efficacy, and pembrolizumab produced marked radiologic tumor regression and complete pathological response in a dMMR tumor. Recent studies also highlight perioperative use in resectable locally advanced head and neck squamous cell carcinoma, where KEYNOTE-689 significantly prolonged event-free survival versus standard of care alone. In gastric cancer, pembrolizumab plus chemotherapy was evaluated in KEYNOTE-859 for untreated advanced HER2-negative gastric or gastroesophageal junction adenocarcinoma, while in metastatic non-small cell lung cancer it is used with chemotherapy as a first-line option. Emerging and translational reports include neoadjuvant use in early-stage triple-negative breast cancer and phase II combination therapy with carboplatin/paclitaxel in metastatic melanoma.
Biomarker-guided immunotherapy
- Mismatch-repair status was described as a critical predictive biomarker for immune checkpoint inhibitor efficacy, including pembrolizumab; in synchronous transverse colon cancers, discordant MMR status was associated with contrasting neoadjuvant responses, including complete pathological response in the dMMR tumor. (PMID:41936028)
- Pembrolizumab’s checkpoint blockade of pd 1 underpins its activity as a neoadjuvant immunotherapy agent in colorectal cancer. (PMID:41936028)
- The literature also notes benefit in pd l1-expressing resectable locally advanced head and neck squamous cell carcinoma, with PD-L1 CPS ≥ 1 highlighted as the responsive subgroup. (PMID:41730003)
Head and neck cancer
- Pembrolizumab was described as an FDA-approved first-line treatment for head and neck squamous cell carcinoma. (PMID:41593888)
- In KEYNOTE-689, perioperative pembrolizumab plus standard of care significantly prolonged event-free survival versus standard of care alone in resectable locally advanced head and neck squamous cell carcinoma. (PMID:41730003)
- The drug is also discussed as part of the evolving cervical cancer therapeutic landscape, with improved survival reported in review-level evidence. (PMID:41958269)
Gastrointestinal cancers
- Pembrolizumab plus chemotherapy was evaluated in KEYNOTE-859 for untreated advanced HER2-negative gastric or gastroesophageal junction adenocarcinoma. (PMID:41964430)
- In colorectal cancer, pembrolizumab was used as neoadjuvant immunotherapy in synchronous transverse colon cancers with discordant mismatch repair status. (PMID:41936028)
- Research trend analyses identify pembrolizumab as an early immunotherapy agent of interest in esophageal cancer. (PMID:41722038)
Thoracic and other solid tumors
- Pembrolizumab was evaluated as a first-line treatment option with chemotherapy for metastatic non-small cell lung cancer. (PMID:41861397)
- In early-stage triple-negative breast cancer, pembrolizumab-based neoadjuvant therapy was associated with pathological complete response, and immune-related adverse events were studied as potential predictors of response. (PMID:42011533)
- A phase II melanoma trial combined pembrolizumab with carboplatin and paclitaxel, with outcomes linked to a mixed inflammatory peripheral signature. (PMID:41732954)