Topotecan has been the standard chemotherapy drug for when SCLC comes back or spreads.
In 2020, the FDA approved the new chemotherapy drug lurbinectedin (Zepzelca) to treat metastatic SCLC that has progressed on or after platinum-based chemotherapy. Lubinectedin works by selectively blocking oncogenic transcription, or the process by which tumor cells reproduce. It interferes with the tumor cells’ reproduction cycle and causes cell death.
Lubinectedin’s approval was based on a phase 2 trial that evaluated the drug’s effectiveness in previously treated patients with advanced solid tumors. The study showed an overall response rate of 35 percent with a median duration response of 5.3 months.
The results of a recent phase 1b/2 trial presented at the World Conference on Lung Cancer in January 2021 showed a combination of lurbinectedin and irinotecan could be an effective second-line treatment for patients. Both patients with platinum-sensitive and nonsensitive disease exhibited improvements, as well as patients with brain metastases. The overall response rate (ORR) was 62 percent.
The safety and efficacy of lurbinectedin in combination with the immune checkpoint inhibitors nivolumab (Opdivo) and ipilimumab (Yervoy) is currently being investigated in a clinical trial among patients with relapsed or recurrent SCLC.
Tyrosine Kinase Inhibitor (TKI): Apatinib
Apatinib (Rivoceranib) is a tyrosine kinase inhibitor (TKI). TKIs decrease tumor growth by blocking tyrosine kinases enzymes, which are used for cell growth and division. Specifically, apatinib works by inhibiting vascular growth in tumor tissue while limiting damage to other cells.
Data from a phase 2 trial presented at the World Conference on Lung Cancer in 2021 showed improved outcomes for patients who have received prior treatment when apatinib is combined with a single-agent chemotherapy. The results showed promising efficacy and high tolerability for patients with advanced SCLC. Patients with limited-stage disease benefited as well, showing higher progression free survival rates (PSF).
This is good news, as the drug currently has Orphan Drug status in the US, with approval pending on the demonstration of efficacy and safety.
TKIs are a type of targeted therapy. Targeted therapies are treatments where the specific genetic makeup of a person’s lung cancer tumor (biomarker or oncogene) defines what treatment works for them. Previously these treatments had not been found helpful for SCLC patients. But with new drugs like apatinib and a new understanding of small cell lung cancer, these treatments could expand soon.