Selective Personalized RadioImmunotherapy for Locally Advanced Non–Small-Cell Lung Cancer Trial (SPRINT)

Author(s): Nitin Ohri, MD, MS¹; Shruti Jolly, MD²; Benjamin T. Cooper, MD³; Rafi Kabarriti, MD¹; William R. Bodner, MD¹; Jonathan Klein, MD¹; Chandan Guha, MD, PhD¹; Shankar Viswanathan, PhD⁴; Elaine Shum, MD³; Joshua K. Sabari, MD³; Haiying Cheng, MD, PhD¹; Rasim A. Gucalp, MD⁵; Enrico Castellucci, MD⁵; Angel Qin, MD⁶; Shirish M. Gadgeel, MD⁷; Balazs Halmos, MD⁵

Source: https://doi.org/10.1200/JCO.23.0062

Dr. Maen Hussein's Thoughts

This is a small trial but really promising in patients with tumors expressing PDL-1 > 50%. We need larger randomized trials and longer follow up. Look at the rate of controlled release (CR) just by induction therapy. Do we really need radiation for those patients? This should be another area to study. Thoughts from radiation oncologists are welcomed.

PURPOSE

Standard therapy for locally advanced non–small-cell lung cancer (LA-NSCLC) is concurrent chemoradiotherapy followed by adjuvant durvalumab. For biomarker-selected patients with LA-NSCLC, we hypothesized that sequential pembrolizumab and risk-adapted radiotherapy, without chemotherapy, would be well-tolerated and effective.

METHODS

Patients with stage III NSCLC or unresectable stage II NSCLC and an Eastern Cooperative Oncology Group performance status of 0-1 were eligible for this trial. Patients with a PD-L1 tumor proportion score (TPS) of ≥50% received three cycles of induction pembrolizumab (200 mg, once every 21 days), followed by a 20-fraction course of risk-adapted thoracic radiotherapy (55 Gy delivered to tumors or lymph nodes with metabolic volume exceeding 20 cc, 48 Gy delivered to smaller lesions), followed by consolidation pembrolizumab to complete a 1-year treatment course. The primary study end point was 1-year progression-free survival (PFS). Secondary end points included response rates after induction pembrolizumab, overall survival (OS), and adverse events.

RESULTS

Twenty-five patients with a PD-L1 TPS of ≥50% were enrolled. The median age was 71, most patients (88%) had stage IIIA or IIIB disease, and the median PD-L1 TPS was 75%. Two patients developed disease progression during induction pembrolizumab, and two patients discontinued pembrolizumab after one infusion because of immune-related adverse events. Using RECIST criteria, 12 patients (48%) exhibited a partial or complete response after induction pembrolizumab. Twenty-four patients (96%) received definitive thoracic radiotherapy. The 1-year PFS rate is 76%, satisfying our efficacy objective. One- and 2-year OS rates are 92% and 76%, respectively. The most common grade 3 adverse events were colitis (n = 2, 8%) and esophagitis (n = 2, 8%), and no higher-grade treatment-related adverse events have occurred.

CONCLUSION

Pembrolizumab and risk-adapted radiotherapy, without chemotherapy, are a promising treatment approach for patients with LA-NSCLC with a PD-L1 TPS of ≥50%.

Author Affiliations

¹Department of Radiation Oncology, Montefiore Einstein Comprehensive Cancer Center, Bronx, NY; ²Department of Radiation Oncology, University of Michigan, Ann Arbor, MI; ³Department of Radiation Oncology, Perlmutter Cancer Center, New York University Grossman School of Medicine, New York, NY; ⁴Department of Epidemiology and Population Health, Montefiore Einstein Comprehensive Cancer Center, Bronx, NY; ⁵Department of Oncology, Montefiore Einstein Comprehensive Cancer Center, Bronx, NY; ⁶Department of Internal Medicine, Division of Hematology-Oncology, University of Michigan, Ann Arbor, MI; ⁷Department of Internal Medicine, Henry Ford Cancer Institute, Henry Ford Health System, Detroit, MI

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