Journal of Clinical Oncology | Phase III PACIFIC-2 Study of Concurrent Durvalumab and Platinum-Based Chemoradiotherapy for Unresectable Stage III Non-Small Cell Lung Cancer

This article summarizes the results of the Phase III PACIFIC-2 clinical trial, evaluating the efficacy and safety of Durvalumab combined with concurrent chemoradiotherapy in patients with unresectable stage III non-small cell lung cancer, providing new clinical evidence for the application of immunotherapy in this field.

 

Literature Overview
The article, titled 'Simultaneous Durvalumab and Platinum-Based Chemoradiotherapy in Unresectable Stage III Non–Small Cell Lung Cancer: The Phase III PACIFIC-2 Study', published in the 'Journal of Clinical Oncology', reviews and summarizes the efficacy and safety of Durvalumab during concurrent chemoradiotherapy in patients with unresectable stage III non-small cell lung cancer (NSCLC). The study aims to explore whether earlier administration of Durvalumab during chemoradiotherapy could further enhance therapeutic outcomes rather than being used solely as consolidation therapy. The original article ends with a Chinese period.

Background Knowledge
For the treatment of unresectable stage III NSCLC, Durvalumab consolidation therapy following concurrent chemoradiotherapy (cCRT) has been established as the standard regimen, significantly prolonging progression-free survival (PFS) and overall survival (OS). However, approximately 27%-50% of patients cannot receive Durvalumab consolidation therapy due to early disease progression, radiation pneumonitis, or other toxicities. Therefore, the researchers hypothesized that initiating Durvalumab earlier during chemoradiotherapy might enhance immune synergy and improve efficacy. This study was designed to test that hypothesis, exploring the potential benefits of combining concurrent immunotherapy with chemoradiotherapy.

 

 

Research Methods and Experiments
This phase III, double-blind, placebo-controlled clinical trial enrolled 328 patients who were randomly assigned in a 2:1 ratio to receive either Durvalumab or placebo, starting from the initiation of concurrent chemoradiotherapy, followed by continuation as consolidation therapy until disease progression. The primary endpoint was progression-free survival (PFS) assessed by blinded independent central review. Secondary endpoints included objective response rate (ORR), overall survival (OS), 24-month overall survival rate (OS24), and safety. The study utilized Kaplan-Meier analysis, with hazard ratios (HR) and 95% confidence intervals (CI) calculated using the Cox proportional hazards model. All analyses were based on the intent-to-treat (ITT) population.

Key Conclusions and Perspectives

• No significant difference was observed in PFS between the Durvalumab and placebo groups (HR=0.85, P=0.247).
• OS analysis also showed no significant difference between the Durvalumab and placebo groups (HR=1.03, P=0.823).
• The ORR was 60.7% for the Durvalumab group and 60.6% for the placebo group (P=0.976).
• Grade 3-4 adverse events were less frequent in the Durvalumab group compared to the placebo group (53.4% vs 59.3%).
• The rate of treatment discontinuation due to adverse events was higher in the Durvalumab group (25.6% vs 12.0%).
• Fatal adverse events were more common in the Durvalumab group (13.7% vs 10.2%), especially within the first four months of treatment.
• The incidence of pulmonary infections or radiation pneumonitis was similar between the two groups (approximately 28.7%–28.8%).
• The study concluded that early administration of Durvalumab during concurrent chemoradiotherapy did not significantly improve efficacy, but the safety profile was consistent with known data.

Research Significance and Prospects
Although Durvalumab did not provide additional efficacy when administered concurrently with chemoradiotherapy, the findings offer important insights for future immunotherapy combination strategies. The study suggests that Durvalumab may still hold value in specific subgroups, requiring further investigation to optimize treatment timing and patient selection. Future studies may focus on earlier immune intervention or combination with other immunomodulators to enhance therapeutic outcomes.

 

 

Conclusion
In patients with unresectable stage III non-small cell lung cancer, the phase III clinical trial of concurrent Durvalumab with concurrent chemoradiotherapy did not significantly improve progression-free survival or overall survival. The study demonstrated that Durvalumab had comparable efficacy to placebo during concurrent therapy, with a safety profile consistent with previously reported data. While Durvalumab did not offer additional benefit during chemoradiotherapy, it remains the standard of care as a consolidation treatment. These results suggest that the use of immune checkpoint inhibitors during concurrent therapy may not be suitable for all patients, and future research should focus on optimizing treatment timing and patient selection strategies.

 

Jeffrey D Bradley, Shunichi Sugawara, Ki Hyeong Lee, Mustafa Özgüroğlu, and on behalf of the PACIFIC-2 Investigators. Simultaneous Durvalumab and Platinum-Based Chemoradiotherapy in Unresectable Stage III Non–Small Cell Lung Cancer: The Phase III PACIFIC-2 Study. Journal of Clinical Oncology.