Immunotherapy (IT) is a transformative cancer treatment approach that uses the body’s own immune system to recognize and attack malignant cells. Unlike traditional therapies that target the tumor directly, IT agents, such as checkpoint inhibitors, essentially remove the “brakes” that cancer cells use to evade immune detection. This strategy has led to remarkable outcomes in certain diseases, but the concept of a single “success rate” is misleading. Efficacy varies widely, depending on the specific cancer type, the individual patient’s biological profile, and the treatment regimen employed. Therefore, evaluating the success of immunotherapy requires a nuanced understanding of how clinical outcomes are measured and the biological factors that dictate response.
Defining Treatment Success Metrics
Oncologists rely on several metrics to gauge the effectiveness of cancer treatment, especially immunotherapy, which often shows unique response patterns. The most definitive measure is Overall Survival (OS), which tracks the length of time patients remain alive from the start of treatment. OS is considered the gold standard because it directly reflects patient benefit.
A second measure is Progression-Free Survival (PFS), the duration a patient lives without the cancer growing or spreading. While PFS indicates how long the therapy controls the disease, immunotherapy can cause a temporary tumor size increase (pseudoprogression) before shrinkage occurs. This makes PFS a less reliable early metric than for other therapies.
The Objective Response Rate (ORR) quantifies the percentage of patients whose tumors shrink to a specific size, including complete and partial responses. Finally, the Duration of Response (DOR) measures how long the tumor remains controlled or undetectable in patients who have responded. The durability of these responses, often lasting for years, is a key feature distinguishing immunotherapy.
Variability Across Cancer Types
The efficacy of immunotherapy is highly dependent on the biological characteristics of the tumor, leading to a wide spectrum of success rates across different malignancies. Some cancers are inherently more “immunogenic,” meaning they generate a strong natural immune reaction that checkpoint inhibitors amplify. This is often linked to a high number of mutations within the tumor cells, which produce unique targets, called neoantigens, for the immune system to recognize.
Cancers like advanced melanoma, non-small cell lung cancer (NSCLC), and kidney cancer show high success rates. In metastatic melanoma, objective response rates (ORR) with single-agent checkpoint inhibitors often range from 35% to 45%, and dual agents can push this range over 50%. Advanced kidney cancer also demonstrates significant responsiveness, with combination regimens showing 18-month overall survival rates exceeding 75% in some trials. A significant subset of advanced NSCLC patients, particularly those with high PD-L1 expression, experiences durable responses, with five-year survival rates reaching 30% or more.
Other cancers show moderate success, where immunotherapy is effective for a smaller portion of patients. In advanced urothelial (bladder) carcinoma, monotherapy checkpoint inhibitors achieve ORRs of approximately 20% to 25%, with one-year overall survival rates around 40%. Recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) also falls into this category, with single-agent ORRs typically ranging from 16% to 20% in previously treated patients, often leading to durable responses.
Conversely, some tumors, such as pancreatic cancer and most forms of prostate cancer, are considered “cold” tumors, exhibiting limited success with single-agent immunotherapy. For unselected patients with metastatic pancreatic cancer, ORRs to checkpoint inhibitors are consistently reported at less than 5%. In metastatic castration-resistant prostate cancer, monotherapy ORRs are also low, typically 3% to 5% in unselected patient populations.
Factors Influencing Individual Outcomes
The success of immunotherapy varies dramatically between patients, often depending on specific biological markers. One common predictive indicator is Programmed Death-Ligand 1 (PD-L1) expression on the surface of tumor or immune cells. High PD-L1 levels suggest the cancer is actively trying to shut down the immune response, making it a good target for blocking drugs.
Another significant marker is the Tumor Mutational Burden (TMB), which measures the total number of genetic mutations within the tumor DNA. A high TMB, particularly above ten mutations per megabase, is frequently associated with a higher likelihood of responding to checkpoint inhibitors, especially in cancers like melanoma and lung cancer.
The presence of Microsatellite Instability-High (MSI-H) or mismatch repair deficiency (dMMR) is a powerful predictor of response. Cancers identified as MSI-H, even those typically resistant to immunotherapy like colorectal or pancreatic cancer, can show remarkable and durable responses regardless of the tumor’s origin. Patient characteristics also contribute to effectiveness and tolerability:
- Overall health
- Pre-existing autoimmune conditions
- Composition of the gut microbiome
Combining Immunotherapy for Enhanced Efficacy
A strategy for improving immunotherapy success involves combining it with other treatments. These approaches aim to increase tumor visibility, generate a stronger immune response, or target multiple immune checkpoints simultaneously. Dual checkpoint inhibition, such as combining a PD-1 inhibitor with a CTLA-4 inhibitor, blocks two separate inhibitory pathways. This often results in higher objective response rates and more durable control compared to using either agent alone, as demonstrated in advanced melanoma and kidney cancer.
The integration of immunotherapy with conventional therapies is also highly effective. Immuno-chemotherapy combines a checkpoint inhibitor with standard cytotoxic chemotherapy, a regimen that is now a first-line standard of care for several cancers, including NSCLC and HNSCC. Chemotherapy kills tumor cells, releasing antigens and effectively turning a “cold” tumor into a “hot” one. Similarly, combining immunotherapy with targeted radiation can induce a localized immune response that sometimes leads to the shrinkage of tumors outside the radiation field, known as the abscopal effect.