Author: Chrystal Lau
Physicians and scientists are constantly striving to improve ovarian cancer treatment through clinical trials. Clinical trials are research studies performed in people that aim to test novel strategies for preventing, diagnosing, and treating disease, as well as improving outcomes and quality of life in patients. This can include testing new drugs and drug combinations, new screening and prevention techniques, new surgical approaches, and more.
While there are so many advancements being made in the medical world, sifting through all of the information and the medical jargon can be frustratingly difficult. In this post, I will be summarizing a few recent clinical trials—what they did and how it turned out—to hopefully give you a small glimpse of what is being done in ovarian cancer research and where we hope to go!
Investigating Cediranib as a Useful Treatment in Front-line and Maintenance Therapy
Researchers conducted a study to test the efficacy (a drug’s ability to produce an effect) and safety of administering oral cediranib (Ricentin®) in combination with platinum-based chemotherapy, and as a continued maintenance treatment, in patients with first relapse of platinum-sensitive ovarian cancer. Cediranib was chosen for this study, because it has shown antitumor activity in recurrent ovarian cancer. It works by serving as an antiangiogenic vascular endothelial growth factor receptor 1-3 inhibitor. So what does this actually mean? Basically, tumors need a robust blood supply in order to grow. This drug blocks the tumors’ ability to get the blood supply they need to thrive.
This study included 456 women aged 18+ in over 63 centers located in Australia, Canada, New Zealand, Spain, and the UK. All patients received up to six cycles of platinum-based chemotherapy (once every 3 weeks) and then entered a maintenance phase. Patients were randomly sorted into one of three groups (Groups A, B, C): placebo + chemotherapy, followed by placebo-only maintenance (Group A – the reference group, 118 women), cediranib 20 mg once-daily + chemotherapy, followed by placebo-only maintenance (Group B, 174 women), and cediranib 20 mg once-daily + chemotherapy, followed by cediranib 20 mg once-daily maintenance (Group C, 164 women). The primary endpoint of this study was to determine if there was a significant difference in progression-free survival between the three groups.
At a 19-month follow-up, 113 (96%) of 118 women assigned to group A had disease progression, compared to 141 (86%) of 164 assigned to group C. Median progression-free survival was about 8 months in group A and 11 months in group C. 156 (90%) of 174 patients in group B had disease progression and a median progression-free survival of about 9 months. While there were reduced rates of disease progression and enhanced rates of progression-free survival, there were some downsides of taking cediranib that motivated many patients to discontinue cediranib. These adverse effects included diarrhea, neutropenia (low white blood cells), hypertension, hypothyroidism, and voice changes. Taking these adverse effects into consideration, researchers still believe that cediranib can provide women with a positive therapeutic option for recurrent ovarian cancer.
High Efficacy and Low Toxicity of Docetaxel/Carboplatin Combo
In another recent study, researchers investigated the efficacy and toxicity of utilizing a modified therapeutic approach to treat recurrent platinum-sensitive disease. In general, recurrent disease is treated with a combination similar to the one used in frontline therapy: paclitaxel (Taxol®, Abraxane®, Onxol®) and carboplatin (Paraplatin®). However, since a high incidence of neurotoxicity has been observed with this treatment, researchers decided to investigate the effects of a new combo—docetaxel (Taxotere®) with carboplatin (Paraplatin®).
Forty patients were enrolled, aged 39-79, and sorted into one of two groups—twenty received the classical paclitaxel/carboplatin regimen (Control group), and the other 20 received the experimental docetaxel/carboplatin regimen (Study group). Study group patients were followed up around 78 months and control group patients were followed up around 62 months.
Researchers found that the study group had a higher overall response rate compared to controls— about 90% in the study patients and about 30% in the control patients. They found complete response rate (the disappearance of all measurable disease for at least 4 weeks) in 60% of study patients and 25% of controls. Study group patients also demonstrated superior 2-year survival rates of 75% compared to the 35% found in controls. Unfortunately, while there were great improvements in overall response and survival rates between patients who received the experimental docetaxel/carboplatin regimen compared to the traditional paclitaxel/carboplatin regimen, there were no differences in toxicity. This led to shared problems between study and experimental groups—hematological toxicity (10% study group, 5% control group), peripheral neuropathy (15% study, 5% control), and some degree of watery eyes (25% study, 0% control). Both groups also experienced similar levels of hypersensitivity reactions to the cisplatin, but patients were successfully treated with desensitization protocol.
Niraparib Maintenance Therapy in Platinum-Sensitive, Recurrent Ovarian Cancer
The European Network for Gynecological Oncological Trial and investigators from the United States, Canada, and Hungary sought to investigate the use of niraparib as a maintenance treatment in patients with platinum-recurrent ovarian cancer. Niraparib is an oral poly (adenosine diphosphate [ADP]-ribose) polymerase (PARP) inhibitor and has shown anti-tumor activity in previous clinical trials.
In this clinical trial, 553 patients were first categorized into two main groups according to the presence or absence of a germline BRCA mutation (gBRCA cohort and non-gBRCA cohort). They were then randomly assigned in a 2:1 ratio to receive niraparib (300 mg) or placebo once daily in 28-day cycles until disease progression was seen. Of the 553 enrolled patients, 203 belonged to the gBRCA cohort, in which 138 were assigned to niraparib and 65 to placebo. 350 patients were categorized into the non-gBRCA cohort, where 234 were assigned to niraparib and 116 to placebo. The primary endpoint of this study was to determine if niraparib can serve as a positive maintenance therapy and can delay disease progression.
Results show that patients receiving niraparib had a significantly longer duration of progression-free survival than those receiving placebo. Within the gBRCA cohort, the niraparib group had a median duration of progression-free survival of 21.0 months, while the placebo group had 5.5 months. In the non-gBRCA cohort, the niraparib group had a median duration of progression-free survival of 12.9 months vs. 3.8 months seen in the placebo group. Patients in the niraparib group (both in the gBRCA and non-gBRCA cohorts) also had longer chemotherapy-free interval and better results on an extended measure of progression-free survival. As you can probably tell from the numbers, niraparib maintenance therapy showed significant activity in keeping disease progression at bay. At this point, it is too early to assess the overall survival effects associated with niraparib, but it is encouraging to see that regardless of whether patients had the germline gBRCA mutation or not, niraparib provided great clinical benefit.
Like with most therapeutic drugs, niraparib did not come without its downsides. Patients taking niraparib were more likely to experience thrombocytopenia (61.3% in niraparib vs. 5.6% in placebo), anemia (50.1% vs. 6.7%), and neutropenia (30.2% vs. 6.1%). Among the patients in the niraparib cohort, the most common thrombocytopenia-associated clinical event was grade 1 or 2 petechiae (5%), which are basically small, speckled bruises. Thankfully, many of the adverse-effects of niraparib occurred within the first three treatment cycles of niraparib, which allowed investigators to adjust dosages and greatly reduce adverse-event frequency. In addition, patient feedback did not reveal any significant difference between the quality of life experienced between patients on niraparib vs. those on placebo. In conclusion, patients with platinum-sensitive, recurrent ovarian cancer had longer progression-free survival when taking niraparib than those in the placebo group, and negative side effects of niraparib could be managed with dose modifications.
I only chose three clinical trials to discuss here; otherwise this blog entry would be several pages long! But there are dozens and dozens of other trials going on and new data being gathered everyday. I hope this blog post gives you insight into some aspects of current ovarian cancer research. In the research world, results can be groundbreaking, but they can also be different from what we hoped for. Still, the body of knowledge surrounding ovarian cancer is growing daily. Many dedicated individuals are working endlessly to gain more answers and to grow our armory of therapies to help those striving to defeat ovarian cancer.