Women with hereditary breast cancer, triggered by the BRCA1 or BRCA2 genes, stand a better chance of survival following successful trials of a drug that cuts the likelihood of the cancer returning after treatment, writes The Guardian.
A major trial carried out by academic researchers to see whether olaparib can prevent recurrence was stopped early – after two-and-a-half years instead of the planned 10 years – when the benefits of the drug became clear. The results, published in the New England Journal of Medicine and presented online at the American Society of Clinical Oncology conference, showed it reduced the relative risk of invasive recurrence, second cancers or death by over 40%.
In absolute terms, 85.9% of women given olaparib in pill form for a year after the end of their treatment remained alive with no return of their cancer for three years, compared with 77.1% on a placebo. The difference was similar when it came to metastatic disease, which is cancers occurring in other places in the body – 87.5% on olaparib and 80.4% on a placebo.
Out of 921 patients on olaparib, 106 had a recurrence of invasive cancer or died by three years, compared with 178 (of 915) patients on a placebo. “In curative therapy trial terms, this is a really major result,” said Prof Andrew Tutt from the Institute of Cancer Research in London, who led the international trial.
For every 100 women treated, it meant, he said, “an extra nine women – let’s say eight or nine women – who are alive and well, without evidence of a recurrence of breast cancer, or the development of any other cancer”.
Until this trial, there was nothing to help women with the inherited breast cancer genes – who are often young and suffer from the most severe forms of cancer – who feared their cancer would return.
Olaparib works by stopping cancer cells from being able to repair their DNA by inhibiting a molecule called PARP, causing cancer cells to die. It works particularly well for patients with faulty versions of the BRCA1 or BRCA2 genes, which are normally involved in another system for repairing DNA. In the trial, significant side-effects were reported to be relatively infrequent.
The drug is already licensed for use in treating genetic forms of breast, ovarian, prostate and pancreatic cancers, although it is expensive and not yet available on the NHS. The researchers hope their study will help speed up a licence for olaparib that will enable all women who have recovered from hereditary breast cancer to take it.
Adjuvant Olaparib for Patients with BRCA1- or BRCA2-Mutated Breast Cancer
Authors: Andrew N.J. Tutt, Judy E. Garber, Bella Kaufman, Giuseppe Viale, Debora Fumagalli, Priya Rastogi, Richard D. Gelber, Evandro de Azambuja, Anitra Fielding, Judith Balmaña, Susan M. Domchek, Karen A. Gelmon, et al., for the OlympiA Clinical Trial Steering Committee and Investigators
Published 3 June in New England Journal of Medicine
Poly(adenosine diphosphate–ribose) polymerase inhibitors target cancers with defects in homologous recombination repair by synthetic lethality. New therapies are needed to reduce recurrence in patients with BRCA1 or BRCA2 germline mutation–associated early breast cancer.
We conducted a phase 3, double-blind, randomized trial involving patients with human epidermal growth factor receptor 2 (HER2)–negative early breast cancer with BRCA1 or BRCA2 germline pathogenic or likely pathogenic variants and high-risk clinicopathological factors who had received local treatment and neoadjuvant or adjuvant chemotherapy. Patients were randomly assigned (in a 1:1 ratio) to 1 year of oral olaparib or placebo. The primary end point was invasive disease–free survival.
A total of 1836 patients underwent randomization. At a prespecified event-driven interim analysis with a median follow-up of 2.5 years, the 3-year invasive disease–free survival was 85.9% in the olaparib group and 77.1% in the placebo group (difference, 8.8 percentage points; 95% confidence interval [CI], 4.5 to 13.0; hazard ratio for invasive disease or death, 0.58; 99.5% CI, 0.41 to 0.82; P<0.001). The 3-year distant disease–free survival was 87.5% in the olaparib group and 80.4% in the placebo group (difference, 7.1 percentage points; 95% CI, 3.0 to 11.1; hazard ratio for distant disease or death, 0.57; 99.5% CI, 0.39 to 0.83; P<0.001). Olaparib was associated with fewer deaths than placebo (59 and 86, respectively) (hazard ratio, 0.68; 99% CI, 0.44 to 1.05; P=0.02); however, the between-group difference was not significant at an interim-analysis boundary of a P value of less than 0.01. Safety data were consistent with known side effects of olaparib, with no excess serious adverse events or adverse events of special interest.
Among patients with high-risk, HER2-negative early breast cancer and germline BRCA1 or BRCA2 pathogenic or likely pathogenic variants, adjuvant olaparib after completion of local treatment and neoadjuvant or adjuvant chemotherapy was associated with significantly longer survival free of invasive or distant disease than was placebo. Olaparib had limited effects on global patient-reported quality of life.
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