The Selective Personalized Radio-immunotherapy for Locally Advanced NSCLC Trial (SPRINT): Initial results.

Abstract

8510 Background: Standard therapy for unresectable locally advanced non-small cell lung cancer (LA-NSCLC) is concurrent chemoradiotherapy followed by adjuvant durvalumab. We performed a prospective trial testing sequential pembrolizumab and risk-adapted radiotherapy without chemotherapy for biomarker-selected LA-NSCLC patients. Methods: Patients with stage III NSCLC or unresectable stage II NSCLC, ECOG performance status 0-1, and no contraindications to protocol-specified therapy were eligible for this trial. Subjects with PD-L1 tumor proportion score (TPS) ≥ 50% underwent baseline FDG-PET/CT, received three cycles of induction pembrolizumab (200 mg, every 21 days), underwent restaging FDG-PET/CT, received risk-adapted thoracic radiotherapy (55 Gy delivered to tumors or lymph nodes with metabolic tumor volume exceeding 20 cc and 48 Gy delivered to smaller lesions, all in 20 daily fractions), and then received up to 13 cycles of additional pembrolizumab. The primary study endpoint was one-year progression-free survival (PFS). Here we report response rates following induction pembrolizumab, PFS and overall survival (OS) rates, and adverse event rates (CTCAE v. 4.03). Results: Twenty-five subjects with PD-L1 TPS ≥ 50% from three institutions were enrolled between August 2018 and November 2021. Median age was 71 (interquartile range [IQR] 62 to 77). One subject had stage II disease, 13 had stage IIIA disease, nine had stage IIIB disease, and two had stage IIIC disease. Median PD-L1 TPS was 75% (IQR 60 to 80%). Two subjects (8%) developed disease progression during induction pembrolizumab, and two subjects discontinued pembrolizumab after one infusion due to immune-related adverse events. Using RECIST 1.1 criteria, 12 subjects (48%) exhibited a partial (n = 11) or complete (n = 1) response following induction pembrolizumab on CT. Using PERCIST criteria, 12 subjects (48%) exhibited a partial response following induction pembrolizumab on PET. Four subjects had responses on PET but not on CT, and four had responses on CT but not on PET. With a median follow-up duration of 13 months, the actuarial 1-year PFS rate is 74%, and the actuarial 1-year OS rate is 95%. Grade 3 adverse events have been limited to single cases of anemia, arthritis, diarrhea, esophagitis, and pneumonitis, and no grade 4-5 adverse events have occurred. Exploratory analyses suggest that response to induction pembrolizumab on PET predicts efficacy of this treatment approach, with a 1-year PFS rate of 100% for responders, compared to 61% for non-responders (logrank p = 0.007). Conclusions: Treatment with pembrolizumab and risk-adapted radiotherapy is a promising treatment approach for LA-NSCLC patients with PD-L1 TPS ≥ 50%. Response on PET following induction pembrolizumab may be useful for identifying patients who can be treated successfully without chemotherapy. Clinical trial information: NCT03523702.