Combining Forces in Small Cell Lung Cancer

Small cell lung cancer (SCLC) makes up about 15% of all lung cancer cases. Although less common, this type spreads much faster and can be more difficult to treat. These patients have fewer treatment options than those with non-small cell lung cancer, so researchers are examining combinations and experimental therapies to help patients live longer.

In clinical trials, PARP inhibitors, which are approved by the Food and Drug Administration (FDA) to treat only certain gynecologic and breast cancers, have shown promise in patients with SCLC. In other studies, findings suggest benefits in combining immunotherapy with chemotherapy.

This year, two immunotherapy drugs were FDA approved to treat certain patients with SCLC based on data from two clinical trials. In March, Tecentriq (atezolizumab) combined with carboplatin and etoposide, both chemotherapy medications, was approved as a first-line treatment for adults with extensive-stage SCLC based on results of the phase 3 Impower133 study. The trial included more than 400 patients and showed a median overall survival of 12.3 months in the group who received Tecentriq plus chemotherapy compared with 10.3 months in those who got placebo plus chemotherapy.

“This regimen has very quickly come into standard practice,” Dr. Anna Farago, a thoracic oncologist at Massachusetts General Hospital Cancer Center and assistant professor of medicine at Harvard Medical School, both in Boston, said in an interview with CURE®.

More recently, in the phase 3 CASPIAN trial, adding Imfinzi (durvalumab) to chemotherapy raised median overall survival to 13 months from 10.3 months with chemotherapy alone in patients with extensive-stage SCLC.

“From both of these studies, we see a consistent result, which is that combination chemotherapy plus an immune checkpoint inhibitor is superior to chemotherapy alone in small cell lung cancer,” Farago said. “Talk to your doctor about whether there is a role for incorporating immune checkpoint inhibitors into your care.”

THE POWER OF PARP INHIBITORS

PARP inhibitors, a type of targeted therapy, are also being investigated in SCLC. The medications inhibit the PARP protein in cancer cells, which is responsible for repairing damaged DNA; unable to fix themselves, tumor cells will die.

Recently, Farago and a team of researchers paired Lynparza (olaparib), a type of PARP inhibitor, with the chemotherapy temozolomide in a phase 2 study that included 50 patients with SCLC who had received at least one prior line of therapy. The response rate was 41.7%, and the researchers noted a median overall survival of 9 months, better than typically expected with chemotherapy alone. In addition, patients lived a median of 4.3 months without their disease worsening.

“There is a signal of activity of PARP inhibitors combined with temozolomide,” Farago said. “This is an exciting potential new treatment pathway for small cell lung cancer. The rationale behind using PARP inhibitors in this disease is that it’s a disease that’s sensitive to inhibition of the DNA damage repair pathway, and the PARP inhibitor/temozolomide combination targets that pathway.”

Using these types of drugs is optimal because they are oral, so patients don’t have to go to a hospital for infusions. However, Farago expressed concern about the frequency of more severe side effects, such as thrombocytopenia (low platelet levels), anemia and neutropenia (low white blood cell count). Patients need to be monitored closely, she said.

Though it’s too early to change the standard of care, the results are exciting and warrant further investigation, according to Farago. Clinical trials can help advances in cancer care make their way to the FDA. “We learn how to better treat patients by doing clinical trials,” Farago said. “Ask your doctor if one is a good option for you, and think about participating, because it can guide us on how to better treat patients going forward.”