Low-dose radiotherapy concurrent with atezolizumab and chemotherapy as first-line treatment for extensive-stage small-cell lung cancer: 3-year follow-up of a multicenter, single-arm, phase 2 trial (MATCH)

Preclinical studies showed that low-dose radiation therapy (LDRT) may act synergistically with immunotherapy in small cell lung cancer (SCLC); however, its role in the treatment of extensive-stage SCLC (ES-SCLC) remains unclear. This single-arm, multicenter, Simon's 2-stage, phase 2 study enrolled treatment-naïve patients with ES-SCLC. Patients received 4 21-day cycles of intravenous cisplatin (75 mg/m2) or carboplatin (area under the curve value, 5 mg/mL/min), etoposide (100 mg/m2), and atezolizumab (1200 mg), with concurrent LDRT (15 Gy in 5 fractions [3 Gy/fraction]), followed by atezolizumab maintenance therapy until loss of clinical benefit, unacceptable toxicity, withdrawal of consent, or death. The primary endpoint was the confirmed objective response rate. The secondary endpoints were progression-free survival (PFS) and overall survival (OS). Fifty-six eligible patients were enrolled between December 16, 2020, and March 30, 2022. The median follow-up was 36.1 months (IQR, 30.9-38.7) at the cutoff date (June 30, 2024). The confirmed objective response rate was 87.5% (95% CI, 75.9-94.8). The median PFS and OS were 6.9 months (95% CI, 5.4-9.3) and 16.9 months (95% CI, 14.0-32.9), respectively. The PFS rates at 1 and 3 years were 27.3% and 20.7%, respectively, and the OS rates at 1 and 3 years were 69.6% and 35.1%. The median depth of tumor response among patients with confirmed objective response was 70.2%. The 3-year OS rates were 57.4% and 18.8% in patients above and below the median depth of tumor response, respectively (hazard ratio, 0.28; 95% CI, 0.13-0.60). The most common treatment-related grades 3 to 5 adverse events were decreased neutrophil count (60.7%) and decreased white blood cell count (58.9%). These findings suggest that upfront LDRT concurrent with atezolizumab plus chemotherapy was effective and tolerable as first-line treatment for ES-SCLC, warranting further verification in randomized controlled trials.