What is the success rate of Durvalumab (Imfinzi) in cancer treatment?

Durvalumab Success Rates in Cancer Treatment

Durvalumab demonstrates a 5-year overall survival rate of 42.9% in stage III non-small-cell lung cancer (NSCLC) after chemoradiation, and achieves objective response rates of 17.8% in metastatic urothelial carcinoma, with success rates varying significantly by cancer type and treatment setting. 1

Stage III Non-Small-Cell Lung Cancer (Consolidation After Chemoradiation)

Survival Outcomes

• Median overall survival (OS) reaches 47.5 months with durvalumab versus 29.1 months with placebo (HR 0.72), representing an 18-month survival advantage in the PACIFIC trial. 1
• The 5-year OS rate is 42.9% with durvalumab compared to 33.4% with placebo, demonstrating durable long-term benefit. 1
• The 5-year progression-free survival (PFS) rate is 33.1% versus 19.0% with placebo, indicating sustained disease control in one-third of patients. 1

Response and Disease Control

• Median PFS is 16.8 months with durvalumab versus 5.6 months with placebo (HR 0.52), representing a clinically meaningful 11-month improvement. 1
• The objective response rate is 28.4% with durvalumab versus 16.0% with placebo, with 72.8% of responders maintaining response at 18 months. 2
• Median time to death or distant metastasis is 23.2 months versus 14.6 months with placebo. 2

Important Caveats for NSCLC

• Post hoc analysis suggests lack of benefit in PD-L1-negative tumors (HR 1.05) and EGFR-mutated patients (HR 0.97), though these analyses were performed in small subgroups and require further validation. 1
• Grade 3 or 4 pneumonitis occurs in only 4.4% of patients, representing the main higher-grade toxicity. 1

Limited-Stage Small Cell Lung Cancer (Consolidation After Chemoradiation)

Survival Outcomes from ADRIATIC Trial

• Median OS is 55.9 months with durvalumab versus 33.4 months with placebo (HR 0.73), representing a 22.5-month survival advantage. 1
• The 24-month OS rate is 68% versus 58.5% with placebo, and the 36-month OS rate is 56.5% versus 47.6%. 1
• The 2-year OS rate improves by approximately 10% with addition of consolidation durvalumab compared to chemoradiotherapy alone. 1

Disease Control

• Median PFS is 16.6 months with durvalumab versus 9.2 months with placebo (HR 0.76). 1
• The 24-month PFS rate is 46.2% versus 34.2% with placebo. 1

Safety Profile in SCLC

• Treatment-related grade 3-4 adverse events occur in 8.8% with durvalumab versus 6% with placebo. 1
• Drug discontinuation due to adverse events occurs in 16.4% versus 10.6% with placebo. 1

Metastatic Urothelial Carcinoma (Second-Line Setting)

Response Rates

• The objective response rate is 17.8% (95% CI 12.7%-24.0%), including 7 complete responses among 191 patients. 3
• Response rates are dramatically higher in PD-L1 high expressors at 27.6% versus only 5.1% in PD-L1 low/negative patients, representing a critical predictive biomarker. 3

Survival Outcomes

• Median OS is 18.2 months with a 1-year OS rate of 55%. 3
• Median PFS is 1.5 months, reflecting the advanced, heavily pretreated nature of this population. 3
• Responses are early (median time to response 1.41 months) and durable (median duration of response not reached). 3

Safety in Urothelial Carcinoma

• Grade 3/4 treatment-related adverse events occur in only 6.8% of patients. 3
• Treatment discontinuation due to adverse events occurs in 1.6% of patients. 3

Metastatic Non-Small-Cell Lung Cancer (First-Line Setting)

MYSTIC Trial Results

• In the first-line metastatic setting, durvalumab monotherapy failed to meet its primary endpoint, with median OS of 16.3 months versus 12.9 months with chemotherapy in PD-L1 ≥25% patients (HR 0.76, P=0.04, nonsignificant). 4
• Durvalumab plus tremelimumab showed median OS of 11.9 months versus 12.9 months with chemotherapy (HR 0.85, P=0.20). 4
• In patients with blood tumor mutational burden (bTMB) ≥20 mutations per megabase, durvalumab plus tremelimumab showed improved median OS of 21.9 months versus 10.0 months with chemotherapy (HR 0.49). 4

Chemotherapy-Ineligible Stage III NSCLC (After Radiotherapy Alone)

DUART Trial Results

• In patients receiving radiotherapy alone (without chemotherapy), median PFS is 9.2 months with 12-month landmark rate of 39.6%. 5
• Median OS is 21.1 months with 12-month landmark rate of 64.7%, demonstrating benefit even in this frailer, older population. 5
• Grade 3/4 possibly related adverse events occur in 9.8% within 6 months of durvalumab initiation. 5

Common Pitfalls and Clinical Considerations

Patient Selection

• Durvalumab should be initiated within 42 days of completing thoracic radiation in stage III NSCLC to maximize benefit. 1
• Patients must have no disease progression after definitive chemoradiotherapy and good performance status (ECOG 0-1). 1
• Consider avoiding durvalumab in EGFR-mutated NSCLC patients based on post hoc analysis, though definitive evidence is lacking. 1

Duration and Monitoring

• Standard treatment duration is up to 12 months in both NSCLC and SCLC settings. 1
• Monitor closely for pneumonitis, which represents the most significant immune-related adverse event. 1

Context-Specific Success Rates

• Success rates are highest in the consolidation setting after chemoradiation (stage III NSCLC and limited-stage SCLC). 1
• Monotherapy in first-line metastatic NSCLC shows inferior results compared to chemotherapy or combination approaches. 4
• PD-L1 expression significantly predicts response in urothelial carcinoma but not in NSCLC consolidation setting. 3, 1