A combination of surufatinib and toripalimab alongside etoposide and cisplatin has shown promising results as a first-line treatment for extensive-stage small cell lung cancer (ES-SCLC). The phase Ib/II study, which included 39 patients, demonstrated a high objective response rate and encouraging survival outcomes, offering a potential new option for this aggressive cancer.
The study, conducted between December 2021 and August 2023, enrolled patients with a median age of 64 years, predominantly men with a history of smoking. The regimen consisted of surufatinib (200 mg daily) combined with toripalimab, etoposide, and cisplatin. Efficacy analysis was performed on 35 patients, while safety was assessed in 38 patients.
Efficacy Outcomes
The objective response rate (ORR) was remarkable at 97.1%, with a disease control rate (DCR) of 100%. All patients experienced tumor shrinkage. The median progression-free survival (mPFS) was 6.9 months (95% CI: 4.6-9.2 months), with a 6-month PFS rate of 50.44% and a 12-month PFS rate of 27.69%. The median overall survival (mOS) was 21.1 months (95% CI: 12.1-30.1 months), with a 12-month OS rate of 66.94%, an 18-month OS rate of 51.39%, and a 24-month OS rate of 38.54%.
Subgroup analysis indicated that patients without liver metastases had a significantly longer mPFS (9.4 months) compared to those with liver metastases (5.7 months, p = 0.0053). A similar trend was observed in patients without bone metastases (8.4 months vs. 5.8 months, p = 0.1927).
Biomarker Analysis
Baseline Ki-67 levels did not significantly influence tumor shrinkage rate, PFS, or OS. However, patients with low levels of serum neuron specific enolase (NSE) and pro-gastrin-releasing peptide (ProGRP) had significantly longer OS (27.1 months vs. 11.4 months, p = 0.0392; NR vs. 12.9 months, p = 0.0225) compared to those with high levels.
Limited data on PD-L1 expression and tumor mutational burden (TMB) suggested that PD-L1 positive or TMB-high patients had numerically longer OS compared to PD-L1 negative or TMB-low cases.
Safety Profile
All patients experienced treatment-emergent adverse events (TEAEs), with 63.2% experiencing grade ≥3 TEAEs. The most common TEAEs (≥20%) were anemia (68.4%), proteinuria (63.2%), decreased white blood cell count (52.6%), hair loss (52.6%), and diarrhea (50.0%). The most common grade ≥3 TEAEs were decreased neutrophil count (31.6%), decreased white blood cell count (23.7%), and decreased platelet count (10.5%). No unexpected adverse events were reported.
