Response rate and local recurrence after concurrent immune checkpoint therapy and radiotherapy for non–small cell lung cancer and melanoma brain metastases

Abstract

BACKGROUND: Prior literature has suggested synergy between immune checkpoint therapy (ICT) and radiotherapy (RT) for the treatment of brain metastases (BrM), but to the authors' knowledge the optimal timing of therapy to maximize this synergy is unclear. METHODS: A total of 199 patients with melanoma and non-small cell lung cancer with BrM received ICT and RT between 2007 and 2016 at the study institution. To reduce selection biases, individual metastases were included only if they were treated with RT within 90 days of ICT. Concurrent treatment was defined as RT delivered on the same day as or in between doses of an ICT course; all other treatment was considered to be nonconcurrent. Multivariable Cox proportional hazards models were used to assess time to response and local disease recurrence on a per-metastasis basis, using a sandwich estimator to account for intrapatient correlation. RESULTS: The final cohort included 110 patients with 340 BrM, with 102 BrM treated concurrently and 238 BrM treated nonconcurrently. Response rates were higher with the use of concurrent treatment (70% vs 47%; P < .001), with correspondingly lower rates of progressive disease (5% vs 26%; P < .001). On multivariable analysis, concurrent treatment was found to be associated with improved time to response (hazard ratio, 1.76; 95% CI, 1.18-2.63 [P = .006]) and decreased local recurrence (hazard ratio, 0.42; 95% CI, 0.23-0.78 [P = .006]). This effect appeared to be greater for melanoma than for non-small cell lung cancer, although interaction tests were not statistically significant. Only 1 of 103 metastases which had a complete response later developed disease progression. CONCLUSIONS: Concurrent RT and ICT may improve response rates and decrease local recurrence of brain metastases compared with treatment that was nonconcurrent but delivered within 90 days. Further study of this combination in prospective, randomized trials is warranted.

International consensus on radiotherapy in metastatic non-small cell lung cancer

“…Chen et al retrospectively analyzed the survival outcomes of patients with NSCLC, melanoma, and renal cell carcinoma (RCC) with BM treated with concurrent SRS and ICI ( 145 ), and reported a superior median OS relative to those who underwent non-concurrent SRS/SRT and ICI (24.7 vs. 14.5 months; P = 0.006) or SRS/SRT alone (24.7 vs. 12.9 months; P = 0.002). These observations echo those of other recent studies ( 148 - 150 ), which suggest concurrent SRS and ICI is the preferred therapeutic strategy to sequential SRS and ICI to maximize the synergy between ICI and radiotherapy for the treatment of patients with BMs. Schapira et al reported patients who underwent concurrent SRS and anti-PD-1 therapy (defined as the receipt of SRS within 1 month of anti-PD-1 therapy) had improved local control and OS compared with those treated with SRS before or after anti-PD-1 therapy ( 150 ).…”

Brain metastases, patterns of intracranial progression, and the clinical value of upfront cranial radiotherapy in patients with metastatic non-small cell lung cancer treated with PD-1/PD-L1 inhibitors

“…To date, numerous studies have been published focusing on the impact and timing of cranial RT in relation to anti- PD-1/PD-L1 therapy for metastatic NSCLC (8,(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25).…”

Update on the Management of Brain Metastasis

“…This has led to incorporation into the ASCO-SNO-ASTRO guidelines for immunotherapy in NSCLC patients with asymptomatic brain metastases [ 38 ]. The use of multi-modality therapy has been shown to be useful in retrospective series compared to either drug alone of radiosurgery alone [ 123 ]. Surgery can remove tumor mass decreasing the need for steroid use [ 100 ].…”