Paclitaxel, carboplatin, and durvalumab in extensive stage small-cell lung cancer (ES-SCLC; IFCT-2203 TAXIO phase II trial): Can we improve the chemotherapy (CT) immunotherapy combination in SCLC?

Abstract

8091 Background: Etoposide+platinum-based CT and anti-PD-L1 is the backbone of ES-SCLC treatment. We hypothesize a deleterious action of etoposide on lymphocyte activation. A “proof-of-concept”, multicenter and single arm phase II trial was designed to assess the efficacy and safety of an etoposide-free chemotherapy combining durvalumab (Durva) to paclitaxel and carboplatin (Pac-Carbo) CT in ES-SCLC. Methods: Patients (pts) with ES-SCLC, PS 0-1 were enrolled and received 4 induction cycles of Durva 1500 mg + paclitaxel 200 mg/m² + carboplatin AUC6 (PCD), every 3 weeks followed by single-agent Durva every 4 weeks until progression or unacceptable toxicity. The primary endpoint was overall survival at 12 months (OS@12m), secondary endpoints were overall response rate (ORR), overall survival (OS), OS at 24 and 36 months, progression-free survival (PFS), duration of response, safety (CTC v5.0) and quality of life (EORTC QLQ-C30 LC13). PFS and ORR were also assessed by independent reviewer committee. To reject the null hypothesis and achieve a 12-month survival rate of at least 34 patients (55.7%), 61 patients were required. Safety was assessed in all patients who received at least one dose of their study treatment. Results: 68 pts were enrolled between Nov 2023 and Feb 2025. Pts characteristics at baseline were: median age 66.6 years; 51.5% female, 67.6% PS1, 19.1% brain metastasis and 51.5% liver metastasis. The median number of cycles was 4 for chemotherapy and 6 for Durva injections. With a median follow-up of 17.1 months, the primary objective was reached. The OS@12m of the first 61 enrolled pts was 57.4% [IC95%: 44.1-70.0]. Median OS was 14.5 months [IC95%: 9.9-17.6]. ORR was 82.4% [IC95%: 73.3-91.4]. Median PFS was 4.6 months [IC95%: 4.4-4.7]. Treatment-related adverse events (TRAE) of grade 3-5 occurred in 48.5% of pts. TRAE leading to death occurred in 2 pts (sepsis). Conclusions: In the IFCT-2203 TAXIO phase 2 trial, the PCD regimen showed a signal of improved OS@12m and reached its statistical objective. Safety findings were consistent with the known safety profiles of all drugs received with no new safety signal for this population. PCD regimen is an active, easy to administer one-day regimen in ES-SCLC and should be integrated in future trials of new IO agents. Pac-Carbo is an alternative to etoposide platinum with potentially better synergy with durvalumab. Clinical trial information: 2023-504670-38-00.