These results suggest that Zejula could increase quality of life in addition to slowing cancer growth.
The study, “Niraparib Maintenance Treatment Improves Time Without Symptoms or Toxicity (TWiST) Versus Routine Surveillance in Recurrent Ovarian Cancer: A TWiST Analysis of the ENGOT-OV16/NOVA Trial,” was published in the Journal of Clinical Oncology.
Zejula, by the GSK company Tesaro, is a PARP inhibitor that works by interfering with cancer cells’ ability to repair their DNA, thereby causing their death. It is a once-daily, oral medicine indicated for maintenance treatment for women with recurrent ovarian cancer who have had a response — complete or partial — to platinum-based chemotherapy.
Its approval by the U.S. Food and Drug Administration in March 2017 was based on data from a Phase 3 clinical trial called ENGOT-OV16/NOVA (NCT01847274). That trial enrolled 533 women with recurrent ovarian cancer, who were given either Zejula or a placebo while responding to platinum-based chemotherapy.
A previous analysis of the trial had shown that, compared with the placebo, Zejula extended the time patients lived before their disease progressed — a measure called progression-free survival. While BRCA mutations make tumors more susceptible to PARP inhibitors like Zejula, people without these mutations also benefited from the treatment, that analysis had also shown.
In the new study, researchers looked at a slightly different measurement, called time without symptoms or toxicity, or TWiST.
TWiST essentially is a measurement of how long a person goes without experiencing toxicities or adverse events — related to the treatment or the disease itself — that would affect quality of life. In a sense, it’s a measurement of how long the disease is not seriously impacting daily living, rather than just assessing time until a tumor starts to grow again.
Mathematically, TWiST was calculated by subtracting the time spent experiencing serious toxicities, such as nausea, vomiting, and fatigue, from progression-free survival time.
“When patients with recurrent ovarian cancer enter remission following platinum-based treatment, they now have the option to extend their progression-free survival with a PARP inhibitor,” Ursula Matulonis, MD, chief of the division of gynecologic oncology at the Dana-Farber Cancer Institute and a study co-author, said in a press release. “It’s really important to demonstrate that, if we’re adding a maintenance therapy, we’re not significantly altering women’s quality of life.”
The researchers calculated TWiST for participants in the trial who did, and did not, have inherited (germline) mutations in the gene BRCA, since these mutations can have a sizable impact on disease course and response to treatment.
For participants with a BRCA mutation, the average TWiST among those given Zejula was 3.8 years, compared with 0.9 years for those treated with a placebo. This meant that Zejula extended TWiST by nearly three years (2.9) in this group.
For those without a BRCA mutation, Zejula extended the average TWiST from 1.1 years to 2.5 years, a difference of 1.4 years.
“Patients receiving niraparib compared with control in ENGOT-OV16/NOVA experienced more time without symptoms or symptomatic toxicities and thus have the potential to experience longer undiminished QoL [quality of life],” the researchers concluded.