Chemo With Benmelstobart Plus Anlontinib Improves Survival Outcomes in ES-SCLC

The treatment combination of benmelstobart and anlotinib with Vepesid (etoposide) plus Paraplatin (carboplatin) as first-line treatment significantly improved survival outcomes for patients with extensive-stage small cell lung cancer (ES-SCLC), according to data from a phase 3 trial.

The researchers from the phase 3 trial, ETER701, analyzed progression-free survival (PFS, time during and after treatment when the disease does not worsen) and overall survival (OS, period from diagnosis or treatment where patients remain alive).

The 738 patients included in the trial with ES-SCLC did not previously receive systemic treatment (treatment for the entire body) and were randomly assigned to two groups: one with a placebo with Vepesid plus Paraplatin and one with benmelstobart and anlotinib with Vepesid plus Paraplatin.

According to clinicaltrials.gov, benmelstobart is a type of monoclonal antibody or checkpoint inhibitor that targets PD-L1, a protein that is found in abnormal amounts on some types of cancer cells.

Anlotinib, according to a study from the journal Oncology Letters, is a “novel oral receptor tyrosine kinase inhibitor targeting vascular endothelial growth factor (a substance made by cells that creates new blood vessels).”

Vepesid and Paraplatin are both chemotherapy drugs, often used to treat SCLC.

Data presented at the 2023 World Conference on Lung Cancer showed that in the intention-to-treat (ITT) population, the benmelstobart regimen resulted in a median PFS of 6.93 months for 246 patients in the study, versus 4.21 months with placebo with Vepesid plus Paraplatin for 247 patients

These findings demonstrated a 68% reduction in the risk of disease progression and death. The six-month PFS rates in the benmelstobart and placebo groups were 59.11% and 16.55%, respectively. The 12-month PFS rates were 27.91% and 2.29%, respectively.

The benmelstobart combination also reduced the risk of death by 39%, versus placebo with Vepesid plus Paraplatin in this population. The median OS was 19.32 months with benmelstobart vs. 11.89 months with placebo. The 12-month OS rates were 64.12% vs. 49.00%, respectively, and the 24-month OS rates were 41.83% vs. 24.24%, respectively.

“The addition of (the) antiangiogenic agent to immunochemotherapy in the first-line treatment of ES-SCLC resulted in the historically longest PFS and OS, supporting the use of immunochemotherapy plus anlotinib as a new treatment option for [this] patient population,” Dr. Ying Cheng, a first-class professor, doctoral tutor and postdoctoral supervisor, as well as chief physician in the department of thoracic oncology at the JiLin Province Cancer Hospital in China, said in a press briefing during the conference.

SCLC is known to be a recalcitrant malignancy, Cheng said, which is a disease that is difficult to detect. Although chemoimmunotherapy regimens have provided 2- to 4-month OS benefits to those with ES-SCLC, approaches that can boost long-term survival are needed.

At the time of the data cutoff of May 14, 2022, 54 patients in the benmelstobart arm were still receiving treatment vs. nine patients in the placebo arm. Moreover, 47.6% and 74.8% of patients, respectively, received subsequent therapy, with 13% and 21.5% of patients, respectively, receiving subsequent immunotherapy.

“The safety profile (of the benmelstobart regimen) is tolerable and manageable,” Cheng noted.

Any-grade treatment-related side effects were experienced by 246 safety-evaluable patients who received the benmelstobart regimen, compared with 246 safety-evaluable patients who were given placebo and Vepesid plus Paraplatin. Treatment-related side effects of grade 3 or higher were experienced by 93.1% and 87% of patients, respectively. In the benmelstobart group, any-grade treatment-related side effects resulted in dose reduction or interruption for 50.4% of patients, any discontinuation in 8.5% and death in 4.5%; in the placebo group, these rates were 23.2%, 2.8% and 1.6%, respectively.

The most common any-grade treatment-related experienced by 10% or more of patients in the benmelstobart and placebo groups, respectively, included decreased platelet count (89% vs 81.7%), decreased white cell count (90.7% vs. 91.5%), weight loss (18.3% vs. 6.9%), increased thyroid hormone levels (13.4% vs 3.3%), positive occult (stool) blood (11.8% vs 6.9%) and decreased lymphocyte (type of white blood cell) count (11.8% vs 9.8%).

“As you all know, seeing separation of survival curves in SCLC like that is quite remarkable and simply something we don’t see often in lung cancer, so hopefully this presentation will be robustly discussed,” Dr. Brendon M. Stiles, moderator and chair of the IASLC Communications Committee, said during the briefing.

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