How effective is immunotherapy (immune therapy) in treating cancer?

Immunotherapy in Cancer Treatment: Effectiveness and Response Durability

Immunotherapy can provide durable, long-lasting responses in cancer patients when effective, functioning like a "vaccine effect" as the immune system "remembers" the cancer, though it doesn't work for all patients. 1

Mechanism of Action and Effectiveness

Immunotherapy works by enhancing the body's own immune response against cancer cells. Key mechanisms include:

• Checkpoint inhibition: Drugs like nivolumab block PD-1 receptors on T cells, releasing PD-1 pathway-mediated inhibition of the immune response against tumors 2
• Immune memory: Unlike conventional therapies, immunotherapies can induce immune memory that propagates a successful rebalancing between tumor and host 1

Response Patterns and Durability

Immunotherapy demonstrates unique response characteristics compared to traditional treatments:

• Durable responses: When effective, immunotherapy can produce long-lasting responses that persist even after treatment discontinuation 1
• Response durability: In Merkel cell carcinoma, immunotherapy shows similar response rates to chemotherapy but with significantly greater durability of response 1
• Memory effect: The immune system "remembers" the cancer similar to a vaccine effect, allowing for continued surveillance and control of cancer cells 1

Effectiveness by Cancer Type

Response to immunotherapy varies significantly by cancer type and patient characteristics:

• Mesothelioma: In non-epithelioid mesothelioma, immunotherapy (ipilimumab plus nivolumab) shows median overall survival of 18.1 months versus 8.8 months with chemotherapy (HR 0.46) 1
• Three-year survival rates: In pleural mesothelioma, 23.2% with immunotherapy compared to 15.4% with chemotherapy 1
• Gynecologic cancers: Immune checkpoint inhibitors have improved outcomes for patients with cervical and endometrial cancers, offering durable responses for some patients 3
• Renal cell carcinoma: Immunotherapy continues to produce durable responses in a subset of patients, with some achieving complete remissions 3

Biomarkers for Response Prediction

Not all patients respond to immunotherapy, making biomarker identification crucial:

• Histology: Non-epithelioid mesothelioma shows dramatically better response to immunotherapy than chemotherapy 1
• MSI-H/dMMR status: Tumors with high microsatellite instability or deficient mismatch repair are highly responsive to immune checkpoint inhibitors 1
• PD-L1 expression: Used to predict response in several cancer types, though not universally reliable 4
• Tumor mutational burden: Higher mutation burden often correlates with better immunotherapy response 4

Safety Profile

Immunotherapy generally has a more favorable toxicity profile than chemotherapy:

• Lower overall toxicity: In head and neck cancer trials, grade 3-5 toxicity was 10.3% for pembrolizumab versus 43.8% for chemotherapy 1
• Treatment-related adverse events: Lower with immunotherapy (61.2%) compared to chemotherapy (87.5%) 1
• Immune-related adverse events: These unique side effects require different management approaches than chemotherapy toxicities 3
• Combination therapy caution: Adding chemotherapy to immunotherapy increases adverse events (RR 1.11) and serious adverse events (RR 1.16) compared to chemotherapy alone 3

Pitfalls and Considerations

Important considerations when evaluating immunotherapy:

• Pseudo-progression: Initial tumor growth followed by response can occur with immunotherapy, requiring modified response criteria 1
• Delayed responses: Benefits may take longer to manifest compared to chemotherapy 1
• Patient selection: Certain autoimmune conditions may contraindicate immunotherapy use 1
• Response evaluation: Traditional RECIST criteria may not accurately capture immunotherapy benefits; immune-modified criteria are preferred 1

Future Directions

The field of immunotherapy continues to evolve:

• Combination approaches: Combining immunotherapies or adding them to other treatment modalities may enhance efficacy 3
• Biomarker refinement: Better predictive markers will improve patient selection 4
• Novel immune targets: Beyond PD-1/PD-L1 and CTLA-4, new immune checkpoints are being investigated 5

Immunotherapy represents a paradigm shift in cancer treatment, offering the potential for durable responses and improved quality of life for responding patients, though careful patient selection and monitoring remain essential.