Efficacy and safety of low-dose radiotherapy (LDRT) concurrent atezolizumab plus chemotherapy as first-line therapy for ES-SCLC : Interim analysis of Phase II MATCH trial.

Abstract

e20611 Background: The IMpower 133 trial represents the current SoC in the 1L setting for pts with ES-SCLC but still needs further efficacy improvement such as objective response rate (ORR, ̃60% in both arms) which may lead to survival benefit. LDRT could play a key role in the priming effect of immune system by acting as an immune adjuvant and having sensitive cytotoxic activity to SCLC. We have reported that LDRT plus ICIs in pretreated ES-SCLC was well tolerated with an improved efficacy. Here we conducted MATCH study to investigate the clinical benefits of adding LDRT to Atezo plus chemotherapy in ES-SCLC pts as 1L therapy. Methods: The MATCH study was a single-arm phase II trial conducted in eight centers across China. A Simon’s minimax two-stage design was adopted. Pts with measurable disease per RECIST v1.1 at baseline with ECOG 0-1 were eligible. Atezo (1200 mg IV, D1) + Cisplatin (75 mg/m2 IV, D1)/Carboplatin (AUC = 5 IV, D1) +Etoposide (100 mg/m2 IV, D1-D3) were administrated on a 21-day cycle for four cycles. Concurrent LDRT (15 Gy/5f) were conducted from D1-D5 in the first cycle. Then pts received Atezo maintenance until loss of clinical benefit or unacceptable toxicity. The primary endpoint was ORR confirmed by investigators after two consecutive evaluations ≥ 4 weeks apart. The secondary endpoints included disease control rate (DCR) and safety. Results: This is the report on the completed 1st phase of the trial. By the cutoff date of 26th August 2021, of the first 21 evaluable pts, 20 were males; mean age was 60.2 y and 85.7% pts had ECOG PS of 1. Previous smokers were 85.7%. Most pts were staged T4 (n = 15, 71.4%), N3 (n = 18, 85,7%) and M1(n = 17, 81.0%). The most common sites of metastasis were bone (47.1%) and liver (11.8%). Median follow-up was 4.0 m (range: 2.6-8.0 m). The confirmed ORR was 95.2% (95% CI, 76.2%-99.9%), among whom all pts were PR. DCR was 100%. The safety profile was consistent with the previous reports. Neutrophil count decreased (66.7%), white blood cell count decreased (42.9%) and anaemia (38.1%) were the most common grade 3-4 adverse events. No grade 5 AE occurred. Two pts experienced AEs leading to treatment withdrawal. IrAEs by preferred term were reported in 3(14.3%) pts: 2 were immune-mediated hyperthyroidism (grade 2) and 1 was immune-mediated enterocolitis (grade 3). No radiation pneumonitis occurred. Conclusions: The study met the response criteria for 1st phase. The combination of LDRT and Atezo plus chemotherapy showed promising benefit and was tolerable in pts with ES-SCLC. The 2nd phase is ongoing. Clinical trial information: NCT04622228.