Is immunotherapy (immunologic therapy) more effective than chemotherapy in terms of success rate and benefits?

Immunotherapy vs. Chemotherapy: Success Rates and Benefits

Immunotherapy demonstrates superior overall survival rates compared to chemotherapy, particularly in certain cancer types and histologies, with fewer severe adverse events and better quality of life outcomes.

Efficacy Comparison

Overall Survival Benefits

• Immunotherapy shows significant overall survival (OS) advantages over chemotherapy in multiple cancer types:
  • In non-epithelioid mesothelioma: 18.1 months with immunotherapy (ipilimumab plus nivolumab) vs. 8.8 months with chemotherapy (HR 0.46) 1
  • In epithelioid mesothelioma: 18.7 months with immunotherapy vs. 16.5 months with chemotherapy (HR 0.86) 1
  • Three-year OS rates of 23.2% with immunotherapy vs. 15.4% with chemotherapy in pleural mesothelioma 1
  • Meta-analyses of NSCLC trials show significantly improved OS and progression-free survival (PFS) with immunotherapy compared to chemotherapy (P<0.0001) 2

Response Patterns and Durability

• While chemotherapy may show initial responses, immunotherapy provides more durable responses:
  • Merkel cell carcinoma studies show similar response rates between immunotherapy and chemotherapy, but immunotherapy provides greater durability of response 1
  • Unique response patterns with immunotherapy include potential pseudo-progression that may be misinterpreted as disease progression with traditional RECIST criteria 1

Toxicity Profile Comparison

Adverse Events

• Immunotherapy generally has a more favorable toxicity profile:
  • In head and neck cancer trials, grade 3-5 toxicity was 10.3% for pembrolizumab vs. 43.8% for chemotherapy 1
  • Treatment-related adverse events were lower with immunotherapy (61.2%) compared to chemotherapy (87.5%) 1
  • However, combination of chemotherapy with immunotherapy increases the incidence of all-grade adverse events (RR 1.11) and serious adverse events (RR 1.16) compared to chemotherapy alone 1

Immune-Related Adverse Events

• Immunotherapy has unique immune-related adverse events (irAEs) that differ from chemotherapy toxicities:
  • irAEs occur in <20% of patients receiving avelumab for Merkel cell carcinoma 1
  • Common high-grade toxicities with chemoimmunotherapy include diarrhea, dyspnea, fatigue, rash, and elevated liver enzymes 1
  • Management strategies for irAEs differ from those for cytotoxic side effects, requiring specialized knowledge 1

Patient Selection and Biomarkers

Predictive Biomarkers

• PD-L1 expression is the primary biomarker for immunotherapy response:
  • High PD-L1 expression (≥50%) predicts better response to single-agent immunotherapy 3
  • Histology also impacts treatment choice - non-epithelioid mesothelioma shows dramatically better response to immunotherapy than chemotherapy 1
  • MSI-H/dMMR tumors are highly responsive to immune checkpoint inhibitors 4

Patient Factors

• Certain patient populations may particularly benefit from immunotherapy over chemotherapy:
  • Patients with poor performance status or elderly patients with targetable mutations may benefit from targeted therapies including immunotherapy 4
  • Patients with contraindications to immunotherapy (such as certain autoimmune conditions) may still require chemotherapy 1

Combination Approaches

Chemoimmunotherapy

• Combining chemotherapy with immunotherapy can provide synergistic effects:
  • Chemotherapy can enhance immunotherapy efficacy by promoting tumor antigen release and presentation 1
  • In pleural mesothelioma, chemoimmunotherapy showed improved median OS (20.1 months) with acceptable toxicity 1
  • For esophageal squamous cell carcinoma, OPDIVO with chemotherapy improved OS compared to chemotherapy alone (HR 0.74) 5

Sequencing Considerations

• Optimal sequencing of immunotherapy and chemotherapy remains under investigation:
  • For patients with non-epithelioid mesothelioma, first-line immunotherapy is preferred 1
  • For patients with epithelioid mesothelioma, either immunotherapy or chemotherapy can be considered first-line 1
  • After progression on chemotherapy, immunotherapy shows benefit as second-line treatment 1

Practical Considerations

Response Evaluation

• Different response criteria are needed for immunotherapy:
  • Traditional RECIST criteria may not accurately capture immunotherapy responses 1
  • Immune-modified response criteria (imRECIST) better assess immunotherapy benefits 1
  • Pseudo-progression may occur with immunotherapy, requiring continued treatment beyond initial progression in some cases 1

Treatment Duration

• Optimal duration of immunotherapy differs from chemotherapy:
  • Immunotherapy is typically continued for up to 2 years in the absence of progression or toxicity 1
  • Chemotherapy is usually given for a fixed number of cycles (4-6) due to cumulative toxicity

Conclusion

When considering immunotherapy versus chemotherapy, immunotherapy offers significant advantages in terms of overall survival, durability of response, and quality of life for many cancer types. The decision should be guided by tumor histology, biomarker status (particularly PD-L1 expression and MSI status), and patient-specific factors. While immunotherapy has revolutionized cancer treatment with its ability to provide durable responses and improved survival with fewer severe toxicities, certain patients may still benefit more from chemotherapy or combination approaches.