PD-1 and Checkpoint Inhibitors May Benefit Some Patients With SCLC

Antibodies such as nivolumab and pembrolizumab that target the programmed cell death protein-1 (PD-1), as well as ipilimumab, which targets cytotoxic T-lymphocyte antigen-4 (CTLA-4), may be promising for patients with small cell lung cancer (SCLC), according to a study published in The Oncologist.¹

“There have been no major changes in the last 5 years. I don’t know if it will be in 12 to 24 months, but within the next 5 years we will hopefully see a checkpoint inhibitor approved,” said lead study author Leora Horn, MD, MSc, associate professor of medicine and clinical director of the thoracic oncology program at the Vanderbilt-Ingram Cancer Center in Nashville, Tennessee.

Preliminary data have shown promising response rates with both nivolumab alone, nivolumab and ipilimumab, and the single agent pembrolizumab, with durable responses and low toxicity profiles. “There are multiple clinical trials, including an ongoing phase 3 study comparing nivolumab to topotecan as second line therapy, a maintenance study after first-line platinum-based therapy with nivolumab or nivolumab/ipilimumab, and a phase 2 trial of pembrolizumab following platinum-based chemotherapy,” said Dr Horn.

She and her colleagues noted that up to 80% of patients respond to first-line chemotherapy, though SCLC is an aggressive lung cancer subtype, and most patients eventually relapse. There are no approved agents beyond the second-line, but researchers hope that will soon change. They report that the identification of molecular targets in SCLC may point to combinations of immune checkpoint inhibitors and new targeted therapies.

“The toxicity profile of these agents in non-small cell lung cancer (NSCLC) is significantly lower than chemotherapy; the same differences are anticipated in SCLC. If approved, they will be a major change, especially for patients with recurrent or extensive stage disease, where there are limited treatment options,” said Dr Horn.

Hossein Borghaei, DO, chief of thoracic oncology and associate professor in the department of hematology/oncology at Fox Chase Cancer Center in Philadelphia, Pennsylvania, said we are moving into a new era in the treatment of SCLC in general, though particularly with immunotherapy. According to Dr Borghaei, there are many potentially active treatments under investigation for SCLC, and the clinical landscape could change very soon.

“It is very hard to estimate survival improvements with immunotherapy,” Dr Borghaei told Cancer Therapy Advisor. “We have had many disappointments before. I think based on what we have seen with immunotherapy agents so far in other diseases and the limited data in SCLC, I am hopeful that we will see improvements in survival.”

M. Catherine Pietanza, MD and colleagues recently reported at 40th Congress of the European Society for Medical Oncology (ESMO) that rovalpituzumab tesirine (Rova-T), which is an antibody drug conjugate (ADC), may be promising for patients who relapse after first-line therapy. Preliminary data suggest positive overall response rates (ORR) with acceptable side effects.²

In this phase 1b SCLC trial, it was found that there was an ORR of 44% and a clinical benefit rate of 78%. The study included 73 patients; researchers found that most common adverse event (AE) was fatigue (6% experienced grade 3 or 4). The researchers noted that the responses were durable and there was a trend toward an improved overall survival (OS).