Stereotactic ablative radiotherapy (SABR) provides >95% local control and has become standard of care for medically inoperable stage I non–small-cell lung cancer (NSCLC). However, cumulatively, approximately 40% of patients develop recurrence in regional lymph nodes, distant organs, or secondary lung cancer. Combined immunotherapy and SABR (I-SABR) may reduce these recurrences by stimulating a stronger cancer-specific immune response.
I-SABR is an ongoing phase 2 randomized study comparing SABR and I-SABR to evaluate the efficacy and toxicity of I-SABR in patients with medically inoperable, early-stage (T1 to T3: <7 cm, including multi-primary tumors), isolated-recurrence NSCLC without lymph node or distant metastasis. The primary objective of the I-SABR trial is event-free survival, where event is defined as any recurrence and/or death. Secondary research objectives include rates of grade ≥2 toxicity. Four-dimensional computed tomography image-guided SABR (50 Gy in 4 fractions or 70 Gy in 10 fractions) was delivered to all patients.
Patients randomized to I-SABR received additional concurrent nivolumab at a dose of 240 mg intravenously every 2 weeks for a total of 7 doses, or 480 mg every 4 weeks for a total of 4 doses. Researchers expect 140 patients to enroll in I-SABR.
To date, 92 patients have enrolled in I-SABR. Their median age is 72 years (range, 57-90 years). These patients were randomized to SABR (N = 47) or I-SABR (N = 45). After median follow-up of 14.5 months (range, 2-28 months), there were no treatment-related grade 4 or grade 5 adverse events. For the I-SABR arm, there was 1 case of possible related grade 3 dyspnea and skin rash, and 2 cases of probable grade 3 fatigue. There were possible or probable treatment-related events, including 2 cases of grade 2 pneumonitis, fatigue, and pruritus, and 1 case of grade 2 hyperthyroidism and arthralgia. No patients discontinued treatment due to adverse effects. Among patients in the SABR arm, there were possible treatment-related events, including 1 case of grade 2 fatigue and pneumonitis. All symptoms resolved with or without treatment.
Nivolumab immunotherapy combined with SABR appears to be well-tolerated in this frail patient population. All toxicities were tolerable and resolved. The major barrier for patient enrollment and/or randomization in this study has been patients’ perception of potential toxicities and additional clinic visits. Continued enrollment and additional follow-up time are needed to validate these safety findings.
Chang JY, Lin SH, Yao L, et al. I-SABR phase II randomized study of nivolumab immunotherapy and stereotactic ablative radiotherapy in early-stage NSCLC: interim analysis of adverse effects. J Clin Oncol. 2020;38:suppl (abstract 9035).