I-SABR phase II randomized study of nivolumab immunotherapy and stereotactic ablative radiotherapy in early stage NSCLC: Interim analysis adverse effects.

Abstract

9035 Background: Stereotactic Ablative Radiotherapy (SABR) provides > 95% local control and has become standard care of medically inoperable stage I NSCLC. However, cumulatively about 40% of patients develop recurrence in the regional lymph nodes, distant organs, or secondary lung cancer. Combined immunotherapy and SABR (I-SABR) may reduce these recurrences by stimulating stronger cancer specific immune response. Methods: This is an ongoing phase II randomized study (SABR vs. I-SABR) to evaluate the efficacy and toxicity of I-SABR in medically inoperable, early stage (T1-T3: < 7 cm, including multi-primary tumors), isolated recurrence NSCLC without lymph node or distant metastasis. The primary objective is event-free survival (any recurrence and/or death). Secondary objectives include rates of ≥Grade 2 toxicity. 4-D CT 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 (240 mg, every two weeks for total of 7 doses or 480 mg every four weeks for total of 4 doses). 140 patients are anticipated to enroll. We report here interim analysis of toxicity. Results: 92 patients (median age: 72, range: 57 to 90) were enrolled and randomized (47 to SABR; 45 to I-SABR). With median follow up of 14.5 months (range 2 to 28 months), there were no treatment-related grade 4/5 adverse events. For the I-SABR arm, there was one case of possible related grade 3 dyspnea, skin rash and 2 cases of probable grade 3 fatigue. There were possible/probable treatment related 2 cases of grade 2 pneumonitis, fatigue, pruritus and 1 case of grade 2 hyperthyroidism and arthralgia. No patients discontinued treatment due to adverse effects. For the SABR arm, there were possible treatment related 1 case of grade 2 fatigue and pneumonitis. All symptoms resolved with or without treatment. Conclusions: Combined Nivolumab immunotherapy and SABR (I-SABR) appear to be well-tolerated in this fragile patient population with no grade 4/5 toxicity. All toxicities were tolerable and resolved. The major barrier for patient enrollment and/or randomization is patient’s perception of potential toxicities and additional clinic visits. Continued enrollment and additional follow up are needed to validate these findings. Clinical trial information: NCT03110978.