P2.02-060 SBRT and Sequential Chemotherapy for Stage IIA to IIIA Non-Small Cell Lung Cancer - A Phase I Dose Escalation Study

Abstract

Stereotactic Body Radiation Therapy (SBRT) has become the standard of care for inoperable early-stage non-small cell lung cancer (NSCLC) due to excellent local control and survival outcomes. Its role in larger tumors is undefined, and patients with inoperable locally advanced NSCLC patients are treated with conventionally fractionated radiation therapy and chemotherapy. Our phase I dose escalation trial evaluates the maximum tolerated dose (MTD) of SBRT in patients with stage IIA to IIIA NSCLC involving a larger primary tumor and/or hilar involvement. Patients with inoperable stage IIA to IIIA (T2b-T4N0M0 and TanyN1M0) NSCLC fit for SBRT and sequential chemotherapy were eligible. SBRT dose escalation levels in a classic 3+3 design were 40Gy, 50Gy, and 60Gy in 5 fractions, delivered every other day. Platinum-based doublet chemotherapy was initiated 6 to 8 weeks after SBRT. The primary endpoint was the MTD based on SBRT-related acute (<3 months) ≥ grade 4 or persistent ≥ grade 3 toxicities (per Common Terminology Criteria for Adverse Events [CTCAE] v4.03). Patient reported outcomes were assessed using the NCI PRO-CTCAE questionnaire. Nine patients were enrolled, three at the 40 Gy and six at the 50 Gy dose level. All patients received SBRT to the prescribed dose. Two patients receiving 50 Gy were no longer eligible for chemotherapy after SBRT. Median follow-up time was 6.3 months (range: 2.5 - 28.9). At the 40 Gy dose level, there was one patient with late (≥3 months post-SBRT) grade 3 pneumonia and one with late grade 3 bronchial obstruction. The dose was escalated to 50 Gy. At the 50 Gy dose level, two patients experienced persistent grade 3 radiation pneumonitis. One patient also had acute grade 4 respiratory insufficiency and contralateral pneumothorax. In the expanded 50 Gy cohort, one patient experienced persistent grade 3 nausea, vomiting, and abdominal pain, and another developed grade 3 chest wall pain. Therefore 50 Gy was determined to be the MTD. On PRO-CTCAE questionnaires patients most frequently reported fatigue (75%), dyspnea (50%), cough (38%), and pain (38%) as interfering “quite a bit” or “very much” with their daily activities. We determined that 50 Gy in five fractions followed by sequential chemotherapy is the MTD for SBRT in patients with stage IIA to IIIA NSCLC. Long-term outcomes and larger trials will be needed to assess whether SBRT results in superior local control and survival compared to conventional chemoradiation. Made possible by the generous support of the DallePezze Foundation.