SBRT Yields Promising Progression-Free Survival in NSCLC With Oligoprogression

Stereotactic body radiotherapy (SBRT) to sites of oligoprogression showed positive benefits to progression-free survival (PFS) for a cohort of patients who had oligoprogressive metastatic non–small cell lung cancer (NSCLC) and breast cancer, according to results presented at a press briefing during the 2021 American Society for Radiation Oncology.¹

At the interim analysis of the first and largest randomized trial regarding the use of radiotherapy for this patient population, the median PFS was 22 weeks in the SBRT arm compared with 10 weeks in the palliative standard-of-care (SOC) arm (P = .005). With a median follow-up was 45 weeks in the entire cohort, 78 of 106 patients had progressed on therapy and 37% (n = 39) of patients had died.

“In this pre-planned interim analysis, we demonstrated the benefit of SBRT to sites of oligoprogression on overall PFS, meeting the primary end point,” C. Jillian Tsai, MD, PhD, lead author of this study from Memorial Sloan Kettering Cancer Center.

Tsai pointed out that with oligoprogression in both tumor types, there is no SOC. For patients with NSCLC that is PD-L1 positive, pembrolizumab (Keytruda) results in a PFS of about 4 months with oligoprogression.² With ramucirumab (Cyramza) plus docetaxel after platinum therapy, PFS for this population is around 4.5 months.³ Additionally, for patients with breast cancer who are given fulvestrant plus a CDK4/6 inhibitor for estrogen receptor–positive disease after first-line endocrine therapy, PFS is between 9.5 to 20.5 months. For those with triple-negative breast cancer who are treated after first-line therapy, there is no SOC and their PFS is between 2.3 to 5.6 months.

The goal of this study was to add SBRT to treatment for patients with 5 or fewer extracranial oligoprogressive lesions. Patients were randomized 1:1 to arm 1 with SOC systemic therapy alone or arm 2 of SBRT to all progressive sites plus SOC systemic therapy.

Patients who received SBRT in addition to SOC had a median PFS of 31 weeks vs 11 weeks in those who did not have SBRT (log-rank P = .002).

Patients with NSCLC who received SBRT plus SOC had a median PFS of 44 weeks compared with 9 weeks in those who did not received SBRT (log-rank P = .001). A total of 40 of 59 patients progressed. Those with breast cancer who received SBRT plus SOC had a median PFS of 18 weeks compared with those who did not received SBRT who demonstrated a median PFS of 19 weeks (log-rank P = .478). A total of 38 of 47 patients progressed.

Forty percent of patients (15 out of 51) in the non-SBRT arm and 61% (23 out of 55) in the SBRT arm had any adverse effect of grade 2 or higher (P = .13). One event each of grade 2 pneumonitis, diarrhea, and gastrointestinal reflux were seen in the SBRT arm vs none in the no SBRT arm (P = .52). Grade 3 dyspnea was observed in 1 patient (2.0%) in the non-SBRT arm and in 0 in the SBRT arm (P = .48).

Forty-five percent of patients with NSCLC (N = 40) experienced new lesions, and 89% of those with breast cancer had (n = 34) of new lesions (P <.001). Patients who were treated with SBRT did not have progression in their lesions that were radiated. Progressing lesions occurred in those who did not receive SBRT or in patients who continued to grow new lesions that were not previously detected.

During this interim analysis, patients with oligoprogressive disease had a longer PFS than with any prior systemic therapy. However, investigators did not find any benefit of SBRT for patients with breast cancer.

“SBRT to oligoprogression had an acceptable toxicity profile. The mechanism of the differential benefits between NSCLC and breast cohorts merits further evaluation,” concluded Tsai.

References

1. Tsai J, Yang T, Guttmann DM, et al. Consolidative use of radiotherapy to block (CURB) oligoprogression: Interim analysis of the first randomized study of stereotactic body radiotherapy in patients with oligoprogressive metastatic cancer of the lung and breast. Presented at: 2021 American Society For Radiation Oncology; October 24-27 2021; Chicago IL. Abstract LBA-3.

2. Langer CJ, Gadgeel SM, Borghaei H, et al. Carboplatin and pemetrexed with or without pembrolizumab for advanced, non-squamous non-small-cell lung cancer: a randomised, phase 2 cohort of the open-label KEYNOTE-021 study. Lancet Oncol. 2016;17(11):1497-1508. doi:10.1016/S1470-2045(16)30498-3

3. Garon EB, Ciuleanu TE, Arrieta O, et al. Ramucirumab plus docetaxel versus placebo plus docetaxel for second-line treatment of stage IV non-small-cell lung cancer after disease progression on platinum-based therapy (REVEL): a multicentre, double-blind, randomised phase 3 trial. Lancet. 2014;384(9944):665-673. doi:10.1016/S0140-6736(14)60845-X