Encouraging results have emerged
from a Phase3 clinical trial that investigated the efficacy of Niraparib, an
orally administered poly ADP ribose polymerase (PARP) inhibitor, in patients
with newly diagnosed advanced ovarian cancer who were at high risk for relapse (González-Martín et al, 2019).
In such patients, Niraparib maintenance treatment resulted in significantly
increasing progression-free survival (the time when the cancer did not progress
further in the patient), compared to those treated with a placebo. Niraparib could
consequently become an integral part in the arsenal against advanced ovarian
cancer.
Ovarian cancer is characterised with the poorest survival rate among all gynaecological cancers resulting in 152,000 deaths worldwide each year. The main treatments for ovarian cancer are surgery, and combination chemotherapy with platinum and paclitaxel. However, up to 85% of the patients with advanced ovarian cancer have a relapse on completing chemotherapy. Even when treatments exist, there are safety concerns, or only a subset of patients is targeted. Therefore, there remains an unmet medical need for the vast majority of patients with advanced ovarian cancer.
The protein, poly ADP ribose
polymerase (PARP), plays a crucial role in DNA repair. PARP helps repair
damaged cells by mending single-strand breaks in the DNA. PARP inhibitors halt
DNA repair in cancer cells leading to cell death. Previous clinical studies
have focussed on PARP inhibitors in tumours with BRCA mutations as fault in
this gene too results in impaired DNA repair. The rationale is that blocking
PARP with a PARP inhibitor in such a context would prevent the cells from repairing
themselves leading to cell death. Therefore, clinical trials had been conducted
in selected patient populations. Niraparib, had been previously shown to be
significantly effective in ovarian cancer patients with BRCA mutations leading
to its regulatory approval. However, recent studies as evident in the PRIMA
trial show that Niraparib is effective in ovarian cancer patients regardless of
BRCA mutations.
The latest clinical trial involved 733
ovarian cancer patients. Patients were at Stages III or IV who have advanced disease and considered to have incurable disease with
chemotherapy alone, including those who had tumors with
homologous-recombination deficiency (with either mutated or unmutated BRCA) and
those with homologous-recombination proficiency. All patients had been previously
treated with platinum-based chemotherapy and had shown response to it. Patients
were randomised and treated with Niprarib or a placebo.
-The median progression-free
survival in patients having tumours with homologous-recombination deficiency,
was 21.9 months in the Niraparib group which was significantly longer than in
the placebo group (10.4 months).
Within the population with
homologous-recombination deficiency, the median duration of progression-free
survival in the subgroup with BRCA mutations was 22.1 months in the niraparib
group and 10.9 months in the placebo group. In the subgroup without BRCA
mutations progression-free survival was 19.6 months with niraprib and 8.2 months on
placebo
-In the subgroup of patients with
homologous-recombination proficiency, the median duration of
progression-free survival was 8.1 months in the niraparib group and 5.4 months
in the placebo group.
In patients with advanced ovarian
cancer in other subgroups with a poor prognosis, including in those who received
neoadjuvant chemotherapy, the median duration of progression-free survival 13.9
(Niraparib) vs. 8.2 months (placebo).
In the overall population, the
progression-free survival was 13.8 months in niraparib group and 8.2 months
with placebo.
References: González-Martín A et al, Niraparib in Patients with Newly
Diagnosed Advanced Ovarian Cancer, N
Engl J Med. 2019 Sep 28.
