Adebrelimab plus chemo almost doubles OS, triples PFS in extensive-stage SCLC

Adding adebrelimab to chemotherapy improves survival outcomes over chemotherapy alone in patients with extensive-stage small-cell lung cancer (SCLC) in the phase III CAPSTONE-1 study presented at AACR 2022. This brings hope to SCLC patients with limited treatment options and poor prognoses.

Adebrelimab nearly doubled the 2-year overall survival (OS) rate and more than tripled the 1-year progression-free survival (PFS) rate.

“Our findings support adebrelimab plus carboplatin and etoposide as a new first-line treatment option for extensive-stage SCLC,” said lead author Dr Ying Cheng from the Jilin Cancer Hospital in Changchun, China. “The progression-free survival [PFS], overall response rate [ORR], and duration of response [DOR] are all favourable in the adebrelimab plus chemotherapy group.”

A closer look at the CAPSTONE-1 population

CAPSTONE-1 investigators compared adebrelimab with placebo, each in combination with carboplatin plus etoposide, as a first-line treatment for extensive-stage SCLC. [AACR 2022, abstract CT038]

A total of 462 patients were randomly assigned to adebrelimab 20 mg/kg (n=230) or placebo (n=232) plus chemotherapy every 3 weeks for 4–6 cycles. This was followed by adebrelimab alone or placebo maintenance therapy every 3 weeks until disease progression, unacceptable toxicity, or the 2-year mark.

In the adebrelimab group, 213 patients ultimately discontinued treatment vs 229 in the placebo group because of disease progression (162 vs 185, respectively), withdrawal of consent (19 vs 22), death (11 vs 4), maximum treatment duration (8 vs 2), investigator decision (7 vs 7), or adverse effects (AEs; 6 vs 7).

Seventeen patients in the adebrelimab group and 3 in the placebo remained on treatment at the data cut-off of October 8, 2021. Median follow-up was 13.5 months in all patients and 22.5 months in patients who were still alive.

Baseline characteristics were similar between the treatment arms. Patients’ median age was 62 years in both arms. Roughly 80 percent of patients were men, had an ECOG performance score of 1, and were former smokers. About 97 percent of patients in each arm had stage IV disease, 32 percent had liver metastasis, and 2 percent had brain metastasis. 

OS, PFS rates

At a median follow-up of 13.5 months, the median OS was 15.3 months with adebrelimab and 12.8 months with placebo (hazard ratio [HR], 0.72; p=0.0017). 

At 1 year, the OS rates were 62.9 percent with adebrelimab and 52.0 percent with placebo. Two-year OS rates were 31.3 percent and 17.2 percent, respectively. 

The median PFS via blinded-independent central review was 5.8 months with adebrelimab and 5.6 months with placebo (HR, 0.67; p<0.0001). At 6 months, the PFS rate was 49.4 percent with adebrelimab vs 37.3 percent with placebo. At 1 year, the PFS rate was 19.7 percent and 5.9 percent, respectively. 

Adverse events

In both treatment arms, the most common treatment-related adverse events (TRAEs) of any grade were haematologic events, alopecia, ALT/AST increase, and gastrointestinal events. 

Grade 3/4 TRAEs occurred in 84.8 percent of those in the adebrelimab arm and 84.1 percent of patients in the placebo arm. Immune-mediated events occurred in 27.8 percent and 17.2 percent, respectively. Each arm had two fatal TRAEs.

Additionally, 12 patients in the adebrelimab group discontinued treatment due to TRAEs vs 9 in the placebo. Two patients in each group had TRAEs that led to death. Additionally, 64 patients in the adebrelimab group had immune-mediated AEs vs 40 in the placebo group.

Common grade 3/4 TRAEs included decreased neutrophil count, decreased white blood cell count, anaemia, and decreased platelet count.