Concurrent chemoradiation with consolidation immunotherapy for localized lung cancer
| Treatment | Schedule | Dose |
| Paclitaxel | Weekly for 6-7 weeks | 45-50 mg/m² |
| Carboplatin | Weekly for 6-7 weeks | AUC 2 |
| Radiation Therapy | Daily for 6-7 weeks | 60-66 Gy in 30-33 fractions |
| Durvalumab (Consolidation) | Every 2 weeks for up to 12 months | 10 mg/kg |
- Chemoradiation phase:
– Paclitaxel and carboplatin are administered concurrently with radiation therapy.
- Consolidation phase (Durvalumab):
– Initiated 1-42 days after completing chemoradiation.
– An alternative dosing schedule of 1500 mg every 4 weeks is also approved.
Trial Results:
The PACIFIC trial, a phase III study, compared durvalumab with placebo in patients with unresectable stage III NSCLC who had not progressed after chemoradiotherapy. Key findings include[1][2][4]:
– Median progression-free survival (PFS): 16.8 months with durvalumab vs 5.6 months with placebo
– Median overall survival (OS): 47.5 months with durvalumab vs 29.1 months with placebo
– 5-year overall survival rate: 42.9% with durvalumab vs 33.4% with placebo
– 5-year PFS rate: 33.1% with durvalumab vs 19.0% with placebo
– Objective response rate: 28.4% with durvalumab vs 16.0% with placebo
– Median time to death or distant metastasis: 23.2 months with durvalumab vs 14.6 months with placebo
These results demonstrate a robust and sustained overall survival benefit and durable progression-free survival with durvalumab following chemoradiotherapy, establishing the PACIFIC regimen as the standard of care for patients with unresectable stage III NSCLC.
Toxicity Profile:
| Adverse Event | Frequency |
| Grade 3-4 neutropenia | 23% |
| Grade 3-4 esophagitis | 21% |
| Grade 3-4 pneumonitis | 9% |
| Any grade immune-related adverse events | 75-96.8% |
| Pneumonitis (any grade) | 33.9-43% |
| Grade 3-4 pneumonitis | 3-15% |
References:
[1] https://ascopubs.org/doi/10.1200/JCO.21.01308
[2] https://pubmed.ncbi.nlm.nih.gov/35108059/
[3] https://pmc.ncbi.nlm.nih.gov/articles/PMC11693428/
[4] https://pubmed.ncbi.nlm.nih.gov/28885881/
[5] https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2817855
[6] https://ascopubs.org/doi/abs/10.1200/JCO.21.01308
[7] https://www.cancer.gov/about-cancer/treatment/clinical-trials/search/v?id=NCI-2024-04361
[8] https://pmc.ncbi.nlm.nih.gov/articles/PMC5949435/