International journal of radiation oncology, biology, physics · 2024
A Phase 2 Single-Arm Trial of High-Dose Precision Targeted Radiation Therapy Added to Immunotherapy for Patients With Metastatic Non-Small Cell Lung Cancer.
СтатьяКлиническое исследование II фазыПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод пока не подготовлен
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Gensheimer Michael F, Kotha Nikhil V, Vitzthum Lucas K, Chin Alexander L, Jackson Scott, van 't Erve Iris, Pratapneni Aniket, Le-Budka My-Linh, Wong Samantha, Brown Eleanor, Barnick Katy, Wakelee Heather A, Das Millie, Ramchandran Kavitha J, Myall Nathaniel J, Padda Sukhmani, Marquez Carol M, Million Lynn, Chen Thomas T, Man Martha C, Cabebe Elwyn C, Chen May Cheng-Su, Hiniker Susan, Hancock Steven L, Swift Patrick S, Diehn Maximilian, Loo Billy W, Neal Joel W
Аннотация
PURPOSE: For metastatic non-small cell lung cancer, the addition of radiation therapy (RT) to immune checkpoint inhibitor (ICI) therapy could have synergistic anti-cancer effects and address the most threatening tumors. We posited that the addition of high-dose RT to ICI could prolong progression-free survival (PFS).
METHODS AND MATERIALS: In this single-arm phase 2 trial, 45 patients with metastatic non-small cell lung cancer who had received an anti-PD-1/anti-PD-L1 ICI for 4+ weeks were enrolled from July 2017 to May 2021. Patients received high-dose RT to 1 to 4 extracranial tumors and continued ICI until progression or unacceptable toxicity. The primary endpoint was PFS at 24 weeks, comparing with a historical control rate of 35%.
RESULTS: Of 44 evaluable patients, median age was 71, 75% had adenocarcinoma, 64% had polymetastatic disease, and 85% of cancers with known PD-L1 percentage were PD-L1-positive. Median number of treated tumors was 2 and most common dose was 40 Gy in 10 fractions (41/81 tumors). Median follow-up was 23.3 months. The trial met the primary outcome: 24-week PFS was 60% (95% CI, 44%-75%), higher than the historical control rate (P < .001). Median PFS was 6.9 months (95% CI, 4.0-13.5 months) and median overall survival was 27.4 months (95% CI, 20.4-not reached). Several patients with prestudy disease progression on ICI treatment achieved durable responses to study treatment, up to 53 months. Local recurrence rate was low: cumulative incidence of 5% at 1, 2, and 3 years. Two dose-limiting toxicities were observed (5%), including 1 grade 5 pneumonitis.
CONCLUSIONS: The strategy improved 24-week PFS compared with historical controls receiving ICI alone. The excellent local control supports the efficacy of high-dose RT in addressing macroscopic disease.
METHODS AND MATERIALS: In this single-arm phase 2 trial, 45 patients with metastatic non-small cell lung cancer who had received an anti-PD-1/anti-PD-L1 ICI for 4+ weeks were enrolled from July 2017 to May 2021. Patients received high-dose RT to 1 to 4 extracranial tumors and continued ICI until progression or unacceptable toxicity. The primary endpoint was PFS at 24 weeks, comparing with a historical control rate of 35%.
RESULTS: Of 44 evaluable patients, median age was 71, 75% had adenocarcinoma, 64% had polymetastatic disease, and 85% of cancers with known PD-L1 percentage were PD-L1-positive. Median number of treated tumors was 2 and most common dose was 40 Gy in 10 fractions (41/81 tumors). Median follow-up was 23.3 months. The trial met the primary outcome: 24-week PFS was 60% (95% CI, 44%-75%), higher than the historical control rate (P < .001). Median PFS was 6.9 months (95% CI, 4.0-13.5 months) and median overall survival was 27.4 months (95% CI, 20.4-not reached). Several patients with prestudy disease progression on ICI treatment achieved durable responses to study treatment, up to 53 months. Local recurrence rate was low: cumulative incidence of 5% at 1, 2, and 3 years. Two dose-limiting toxicities were observed (5%), including 1 grade 5 pneumonitis.
CONCLUSIONS: The strategy improved 24-week PFS compared with historical controls receiving ICI alone. The excellent local control supports the efficacy of high-dose RT in addressing macroscopic disease.