Experimental Drug Combination Shows Potential in Early-Phase Trial of Lung, Ovarian Cancers

Researchers may have found a potential new way to treat patients with ovarian or lung cancer who had previously failed other treatments, according to early trial findings published in Annals of Oncology.

The drug combination of vistusertib (AZD2014) plus Taxol (paclitaxel) stopped cancer from progressing for nearly six months. Additionally, tumors shrank in more than half of patients with ovarian cancer and in more than a third of patients with lung cancer.

“The trial showed tolerable schedules in expansion cohorts of over 20 patients,” the study authors wrote. “The response rates and progression-free survival in these non-randomized phase 1 expansions show promise.”

Vistusertib, an oral drug that attacks the protein mammalian target of rapamycin (mTOR), was tested in combination with the chemotherapy drug Taxol in 25 women with high-grade, serous ovarian cancer and 40 people with squamous non-small cell lung cancer (NSCLC).

Researchers from The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust, both in London, studied the dosing schedule of vistusertib across two schedules to determine safety and found it to be well tolerated. The most common side effects across both schedules were grade 1/2 fatigue, nausea, anemia and diarrhea.

In the group of patients with ovarian cancer, 12 percent of patients were platinum refractory, meaning they did not respond to that particular anticancer therapy; 48 percent had progressed within 6 months of the last platinum treatment and 96 percent had progressed within a year of their last platinum treatment. However, when given vistusertib and Taxol, 52 percent of patients responded to the treatment.

“This phase 1 study of recurrent, ovarian cancer patients shows that the combination of standard Taxol plus a new biological drug, vistusertib, results in tumor shrinkage in over 50 percent of the 25 patients treated,” Rick Boulay, M.D., chief of gynecologic oncology at the Lehigh Valley Health Network, who is not an author on the study, said in an interview with CURE. “Though the drugs’ activity is much higher than expected and the side effects were well tolerated, unfortunately, the tumor shrinkage, on average, lasted slightly less than six months.”

In the lung cancer group, 35 percent of patients responded. “These data exceed traditional outcomes for the squamous NSCLC population beyond first-line therapy and demonstrate potential for benefit and warrant further evaluation,” the study authors wrote.

Previous research has found that chemotherapy-resistant ovarian cancers typically have high levels of the molecule p-S6K, according to a press release. That molecule helps cancer cells grow. The proteins mTOR1 and 2, which vistusertib blocks, “turn on” p-S6K. However, if mTOR1 and 2 are blocked, cancer cells can’t use p-S6K to grow, the researchers explained.

“This study is a significant step forward in researchers’ understanding of manipulating the abnormal genes in ovarian cancer cells, causing those cells to temporarily stop growing,” said Boulay. “However, more work is required to find where to best use vistusertib and other novel biological drugs in the treatment of ovarian cancer. To best answer these questions and possible improve individual cancer outcomes, we encourage patients to enroll in clinical trials such as this one.”

A phase 2 trial is currently underway that is testing the combination therapy in a larger group.