Applauded as potentially practice changing, data from the phase III SOLO-1 multi-center clinical trial* that counted on the participation 19 internationally renowned experts across 10 countries, were presented today during the ESMO Congress Presidential Symposium co-chaired by VHIO’s Director, ESMO and ESMO Congress President, Josep Tabernero, and the Society’s Past President, Fortunato Ciardiello.
Led by Kathleen Moore, Associate Professor at the Stephenson Oklahoma Cancer Center (USA), and co-authored by Ana Oaknin, Principal Investigator of VHIO’s Gynecological Malignancies Group, findings from the SOLO-1 study that enrolled 391 patients with advanced serous or endometrioid ovarian cancer, provide fresh hope for patients with high-grade ovarian cancer.
More specifically, maintenance therapy with PARP inhibitor, olaparib, has not only shown an unprecedented extension of progression-free survival (PFS) by 3 years in over 50% of patients with newly diagnosed and advanced ovarian cancer, but also reduced the risk of disease progression by an impressive 70%.
Ovarian cancer is the eighth most commonly occurring cancer in women and ranks eighteen among the most commonly occurring cancer overall, with an estimated 300,000 new cases this year. Additionally, up to 80% of all cases are diagnosed at advanced stages of disease, with 20% of these patients carrying a BRCA mutation in either of the BRCA1 and BRCA2 genes.
Currently standard treatment consists of cytoreductive surgery followed by carboplatino/paclitaxel +/- bevacizumab chemotherapy. At first, patients respond to this regimen but between 70-80% of them unfortunately relapse within an estimated 3 years following initial diagnosis.
Commenting for VHIO Communications, Ana Oaknin, co-author and investigator of the study, observed, “This pivotal study has triumphed by spectacularly improving PFS compared with other therapies used to treat this particular subgroup of patients. Importantly too, maintenance with olaparib was shown to be well tolerated by the majority of patients.”
Highlighting the relevance of results and the where-to-next, she continued, “Our research marks critical progress in improving the prognosis and outcomes for these patients. Moving forward, we are already extending our approach to a broader group of patients with high grade serous or endometrioid ovarian carcinoma and exploring the efficacy of olaparib maintenance in combination with chemotherapy.”
Serving as additional testament to the practice changing potential of these findings, this present study was selected by ESMO for its Congress Media Program and was also timed to publish as an open access Original Article today by The New England Journal of Medicine**.
Ana was also interviewed by ESMO for one of its Expert Video Reports. As co-author of the study she commented on the importance of the reported findings and outlined some next step directions. To access this interview click here.
To discover more, please also see ESMO’s official press release below.
* LBA7_PR. Maintenance olaparib following platinum-based chemotherapy in newly diagnosed patients (pts) with advanced ovarian cancer (OC) and a BRCA1/2 mutation (BRCAm): Phase III SOLO1 trial. K.N. Moore, N. Colombo, G. Scambia, B.-G. Kim, A. Oaknin, M. Friedlander, A. Lisyanskaya, A. Floquet8, A. Leary, G.S. Sonke, C. Gourley, S. Banerjee, A.M. Oza, A. González-Martín, C. Aghajanian, W. Bradley, E.S. Lowe, R. Bloomfield, P. DiSilvestro.
** Maintenance Olaparib in Patients with Newly Diagnosed Advanced Ovarian Cancer. Kathleen Moore, M.D., Nicoletta Colombo, M.D., Giovanni Scambia, M.D., Byoung-Gie Kim, M.D., Ph.D., Ana Oaknin, M.D., Ph.D., Michael Friedlander, M.D., Alla Lisyanskaya, M.D., Anne Floquet, M.D., Alexandra Leary, M.D., Gabe S. Sonke, M.D., Ph.D., Charlie Gourley, M.D., Ph.D., Susana Banerjee, M.D., Ph.D., Amit Oza, M.D., Antonio González-Martín, M.D., Ph.D., Carol Aghajanian, M.D., William Bradley, M.D., Cara Mathews, M.D., Joyce Liu, M.D., Elizabeth S. Lowe, M.D., Ralph Bloomfield, M.Sc., and Paul DiSilvestro, M.D. October 21, 2018. DOI: 10.1056/NEJMoa1810858
Source: The European Society for Medical Oncology (ESMO)
Olaparib maintenance extends progression-free survival by estimated 3 years in advanced ovarian cancer
Munich, Germany, 21 October 2018 – Two-year maintenance therapy with olaparib, a PARP (poly ADP ribose polymerase) inhibitor, olaparib, led to a substantial, unprecedented improvement in progression-free survival (PFS) in newly diagnosed patients with advanced ovarian cancer and a BRCA1 or 2 mutation, results from the phase 3 SOLO-1 trial show. (1)
“The median PFS for patients who received placebo was only 13.8 months while the median PFS for those who received olaparib was not reached but looks to be approximately three years longer than the placebo group [HR was 0.30; 95% CI: 0.23, 0.41; p<0.0001],” reported Dr Kathleen Moore, Associate Professor at the Stephenson Cancer Center, University of Oklahoma, US, presenting the results at ESMO 2018 Congress.
“While it is too early to say whether we have impacted the fraction of women who could be cured with their front-line therapy, the fact that it is estimated that over 50% of women on the olaparib arm were still progression free at four years as compared to only 11% for placebo speaks to this hope,” she remarked. “The results of SOLO-1 herald a new era in treatment for women diagnosed with advanced ovarian cancer who carry a BRCA mutation [a mutation in either of the BRCA1 and BRCA2 genes]. This study demonstrates an outstanding improvement in PFS over placebo which is maintained even after the olaparib is stopped at two years,” added Moore.
SOLO-1 is the first, double-blind, randomised, prospective phase 3 evaluating front line olaparib maintenance therapy after platinum-based chemotherapy in newly diagnosed advanced ovarian cancer (FIGO stage III–IV) with a BRCA mutation. “It provides the first large dataset of prospectively collected outcomes for this population of women,” said Moore.
A total of 391 patients with high grade serous or endometrioid ovarian cancer who were in clinical complete or partial response after chemotherapy upon entering the study, were randomised, 2:1, to olaparib tablets 300 mg bd (n=260) or placebo (n=131) for two years. The primary endpoint was investigator-assessed PFS from randomisation. Secondary outcomes included PFS2, which was time from randomisation to the second progression event a patient might experience; overall survival; and quality of life. Median follow-up was 41 months.
PFS2 remained significantly improved among patients who had received olaparib maintenance with a median PFS2 of 41.9 months for placebo versus median not reached for the olaparib group (HR: 0.50; 95%CI: 0.35, 0.72; p=0.0002).
The most common grade ≥3 toxicities with olaparib were anaemia (22%) and neutropenia (8%). There was no clinicaly relevant change in quality of life between groups and dosing was well tolerated with only 12% of patients discontinuing olaparib due to toxicity and not disease progression. Furthermore, there was no detriment to quality of life.
“These are outstanding results in a worsening disease setting. Not only was olaparib efficacious but it was also shown to be well tolerated,” said Prof Isabelle Ray-Coquard, from Université Claude Bernard Lyon Est, Lyon, France, commenting on the results for ESMO. “The findings promise to change practice in this subgroup of patients with a BRCA mutation.”
“Now, two questions remain. Can we expand this benefit to all high-grade serous carcinomas? Looking at existing results in relapse with PARP inhibitor maintenance in all comers, we can anticipate excellent results for all patients with high grade serous or endometrioid ovarian carcinoma,” added Ray-Coquard. “Also, what is the best maintenance therapy? Standard first line therapy in many countries is chemotherapy plus bevacizumab maintenance for the majority of advanced disease, but the question remains whether maintenance with olaparib alone, or in combination with bevacizumab is preferable. The PAOLA 1 trial will provide some information, and will probably be available next year.”