Which Cancers Respond Best to Checkpoint Inhibitors?

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Which Cancers Respond Best to Checkpoint Inhibitors?

By Peter Teoh, Science Writer

The strongest and most consistent responses to checkpoint inhibitors are seen in a handful of highly immunogenic advanced cancers, plus any advanced solid tumor with certain DNA-repair defects. Responses vary a lot by cancer type and by individual. pmc.ncbi.nlm.nih

Cancers with best-established benefit

These are the advanced/metastatic cancers where checkpoint inhibitors have become core, often first-line, treatment because of relatively high response rates and durable control:

• Melanoma and some other advanced skin cancers (e.g., Merkel cell carcinoma, cutaneous squamous cell carcinoma) show some of the most durable responses and long-term survivals with PD-1/PD-L1 and CTLA-4 blockade, especially with combinations. pmc.ncbi.nlm.nih
• Non-small cell lung cancer (NSCLC) has robust benefit, particularly when PD-L1 expression is high, with response rates around 40-50% for some PD-1/PD-L1 regimens. sciencedirect
• Kidney (renal cell) cancer responds well, and ICI-based combinations (PD-1/PD-L1 inhibitors alone or with CTLA-4 or targeted VEGF/tyrosine-kinase inhibitors) are standard for metastatic disease. ascopubs
• Bladder (urothelial) cancer shows meaningful responses and survival gains in advanced stages, and checkpoint inhibitors are widely used after or instead of chemotherapy. pmc.ncbi.nlm.nih
• Hodgkin lymphoma has very high response rates to PD-1 blockade because of strong PD-L1/PD-L2 expression driven by genetic changes. cancer

Other solid tumors with clear, but more selective, benefit

Several other advanced cancers benefit from checkpoint inhibitors, but often only in subsets or in combination with chemotherapy/targeted therapy:

• Liver (hepatocellular) cancer: atezolizumab plus bevacizumab and other ICI-based regimens improve progression-free and overall survival vs older systemic therapies. pmc.ncbi.nlm.nih
• Triple-negative breast cancer: benefit mainly in PD-L1-positive disease, especially when pembrolizumab is combined with chemotherapy. cancer
• Head and neck squamous cell carcinoma: PD-1 inhibitors improve survival in recurrent/metastatic disease versus standard chemotherapy. mdanderson
• Esophageal and gastric cancers: PD-1/PD-L1 inhibitors, often with chemotherapy, improve outcomes in PD-L1-expressing advanced disease. mdanderson
• Some gynecologic cancers (e.g., endometrial) and others like small-cell lung cancer also have approved ICI indications, usually in biomarker-defined or treatment-line-specific settings. blog.dana-farber

DNA-repair-deficient and MSI-H tumors (any primary site)

A special group that tends to respond unusually well are advanced solid tumors that are:

• Microsatellite instability-high (MSI-H) or mismatch-repair deficient (dMMR)
• Have very high tumor mutational burden

These tumors produce many abnormal proteins (neoantigens), making them highly visible to the immune system once checkpoints are blocked. PD-1 inhibitors are approved in a “tumor-agnostic” way here, meaning any advanced solid tumor with MSI-H/dMMR status can be treated regardless of where it started (colon, endometrium, stomach, etc.). pmc.ncbi.nlm.nih

Tumors that generally respond poorly

Some common advanced cancers, such as microsatellite-stable (MSS) colorectal cancer and many pancreatic cancers, usually have low response rates to checkpoint inhibitors unless special features (like MSI-H, high mutational burden, or specific combinations in trials) are present. In these, ICIs are mainly used in biomarker-defined subgroups or clinical trials rather than as routine therapy. blog.dana-farber