ASCO 2016: Targeted therapy shows efficacy in advanced small cell lung cancer

by Bruce Sylvester: Investigative rovalpituzumab tesirine (Rova-T) appears to be safe and shows efficacy in treating advanced small cell lung cancer (SCLC), researchers reported in June, 2016 at American Society of Clinical Oncology (ASCO) Annual Meeting.

Notably, subjects responded better to treatment when their tumors expressed high levels of delta-like protein 3 (DLL3), the protein that rovalpituzumab tesirine  targets.

“The goal is always to give the right patient the right drug at the right time, but patients with advanced small cell lung cancer have not benefited from any of the new targeted therapies available to patients with other types of cancer,” said investigator Charles Rudin, MD, PhD, Chief of the Thoracic Oncology Service at Memorial Sloan Kettering Hospital in New York, “They desperately need new treatment options, so the ability to predict whether a patient might respond to Rova-T by testing their tumor for overexpression of the DLL3 protein is crucial because it may ultimately help us give this drug to the patients most likely to benefit from it, and avoid giving it to patients who won’t.”

As background, the authors noted that the DLL3 protein is highly expressed in approximately two-thirds of SCLC tumors. Rovalpituzumab tesirine binds to DLL3 on the surface of tumor cells and delivers a toxic load into each cell.

The investigators enrolled 74 subjects with SCLC that had progressed after at least one course of therapy.

Of 60 evaluable patients treated with doses in the active range of 0.2-0.4 mg/kg, 68 percent achieved at least stabilization/non-worsening of disease, and 18 percent achieved significant tumor reductions.

Twenty-six evaluable patients had tumors that overexpressed DLL3, and 89 percent of them achieved. stable/non-worsening disease, while 39 percent achieved significant tumor reductions.

Twelve of the subjects whose tumors overexpressed DLL3 received rovalpituzumab tesirine as third-line treatment. No approved third-line therapy yet exists. Half of these subjects achieved significant tumor reductions, and 92 percent experienced at least stabilization/non-worsening  of disease. Four of these patients lived over six months, and two lived for at least 18 months.

Treatment side effects were manageable.