Serplulimab Delivers the Best Results Yet in Small Cell Lung Cancer

Small cell lung cancer is one of the two main types of lung cancer and tends to grow rapidly and spread early. Small cell lung cancer (SCLC) usually occurs in people who smoke heavily and accounts for around 15-20% of all lung cancers.

SCLC consists of clusters of cells that appear small under the microscope. Compared with non-small cell lung cancer (NSCLC), the other main lung cancer type, SCLC grows and spreads more quickly. A more aggressive treatment plan is therefore generally used after an SCLC diagnosis. Most cases are diagnosed at an advanced stage and tend to develop early metastases.

The standard treatment of advanced SCLC changed following FDA approval of atezolizumab immunotherapy in March 2019, and chemotherapy plus immunotherapy has now become the most effective known first-line option. This article discusses a new immunotherapy agent for advanced SCLC: serplulimab.

Hansizhuang, whose active ingredient is serplulimab, is an intravenously administered immunotherapy developed for solid tumours by the Chinese biotechnology company Shanghai Henlius. It is an anti-PD-1 antibody. Serplulimab’s first approval covered adults with advanced, unresectable or metastatic microsatellite instability-high (MSI-H) solid tumours that had not responded to previous standard treatments. It received this approval in China on 25 March 2022. Although applications have been submitted, it has not yet received FDA or European Medicines Agency (EMA) approval.

The ASTRUM-005 Study

On 27 September 2022, JAMA published an interim analysis of the phase III ASTRUM-005 trial by Cheng and colleagues. Adding the PD-1 inhibitor serplulimab to chemotherapy improved overall survival in first-line treatment of advanced small cell lung cancer.

Study Details

The double-blind trial included 585 patients at centres in China, Georgia, Poland, Russia, Türkiye and Ukraine. Overall, 67% of patients in the serplulimab group and 71% in the control group were Asian.

Survival Results

At the October 2021 data cutoff for the interim analysis, median follow-up was 12.3 months, with a range of 0.2-24.8 months.

• Median overall survival was 15.4 months in the serplulimab group (95% confidence interval [CI] = 13.3 months to not evaluable) and 10.9 months in the control group (95% CI = 10.0–14.3 months), with a hazard ratio [HR] of 0.63 (95% CI = 0.49–0.82; P < 0.001).
• By independent radiology review, median progression-free survival was 5.7 months with serplulimab (95% CI = 5.5–6.9 months) and 4.3 months with placebo (95% CI = 4.2–4.5 months), with HR = 0.48 (95% CI = 0.38–0.59).
• Objective responses occurred in 70.4% versus 80.2% of patients, and complete responses in 0% versus 0.8%.
• Median response durations were 5.6 versus 3.2 months.

Adverse Effects

Treatment-related grade ≥ 3 adverse effects occurred in 33.2% of the serplulimab group and 27.6% of the control group. Immune-related adverse effects of any grade were reported in 18.4% versus 37% (grade ≥ 3, 9.5% versus 5.6%). Hypothyroidism (11.6% versus 1.5%) and hyperthyroidism (9.0% versus 3.1%) were more common with serplulimab. Deaths attributed to serplulimab-related adverse effects occurred in three patients (0.8%), due to acute coronary syndrome, pyrexia and decreased platelet count.

Commentary

In initial treatment of advanced small cell lung cancer (SCLC), adding immunotherapy to chemotherapy is now standard. Atezolizumab (Tecentriq) received approval for this use in 2019, followed by FDA approval of durvalumab (Imfinzi) in 2020. Both drugs are also licensed by the Turkish Ministry of Health for this purpose, but they have not yet been included in reimbursement coverage.

Before immunotherapy, median overall survival in this setting was around 10 months; with serplulimab, it now exceeds 15 months.

Below is an indirect comparison of the results of 3 notable first-line studies in advanced SCLC.