FORCE has a strong commitment to promoting research to benefit our community. We advocate for more research funding, educate people about available studies, and report findings back to our community.
by Piri Welcsh, PhD
ENGOT- OV16/NOVA trial revisited
The previously reported ENGOT-OV16/NOVA phase III trial compared the PARP inhibitor niraparib versus placebo as maintenance treatment in patients with recurrent, platinum-sensitive ovarian cancer. This study showed that niraparib was associated with a significantly longer progression-free survival (PFS) than placebo, regardless of BRCA mutation status.
A new study assessed the long-term benefit of niraparib for recurrent ovarian cancer among patients who participated in the ENGOT-OV16/NOVA trial. This study evaluated PFS at 12, 18, and 24 months. At each of these intervals, regardless of BRCA mutation status, the percentage of disease-free patients was always higher among those receiving niraparib vs placebo.
Results of another study that also analyzed the initial ENGOT-OV16/NOVA results suggest that ovarian cancer patients who have only a partial response to chemotherapy can significantly benefit from niraparib when it is used as maintenance therapy.
SOLO2 trial revisited
The previously reported SOLO2 phase III trial compared olaparib to placebo in BRCA mutation carriers who had relapsed ovarian cancer that was sensitive to platinum therapy. SOLO2 showed a significant difference in PFS for olaparib vs placebo. However, this benefit comes at a cost, which is toxicity. For olaparib, specific toxicities included nausea, vomiting, and fatigue based on findings from earlier studies.
New findings that looked at the combined benefit of PFS plus quality of life were presented. Analysis of the SOLO2 data demonstrated a clear benefit for olaparib treatment over placebo when adjusting for patient-reported quality of life. Patient-centered benefits were further evaluated by means of the time without symptoms of disease or toxicity. Despite the toxicity associated with olaparib, results indicate a longer period of time without cancer-related symptoms or treatment toxicity for patients in SOLO2 who were treated with olaparib.
OlympiAD trail phase II trial
Results of late-phase development of PARP inhibitors for BRCA mutation carriers who develop breast cancer were reported. The OlympiAD clinical trial was designed to assess the efficacy and safety of olaparib in HER2-negative metastatic breast cancer patients with an inherited BRCA mutation. The results of this trial indicated that olaparib provided significantly prolonged progression-free survival benefit compared to physicians’ choice of a standard of care chemotherapy among BRCA mutation carriers with HER-2 negative-metastatic breast cancer. The trial showed that the risk of disease worsening or death was reduced by 42% in patients who were treated with olaparib compared to those who received chemotherapy.
ABRAZO phase II trial
Results of the phase II ABRAZO clinical trial that studied the effectiveness and safety of talazoparib, an investigational, dual-mechanism PARP inhibitor, were presented. This study was open to BRCA mutation carriers with metastatic triple-negative breast cancer (TNBC) who failed at least two prior chemotherapy treatments or were previously treated with a platinum regimen. The results showed that talazoparib was well tolerated and may have clinical benefit for patients who have a BRCA mutation and TNBC. Talazoparib is being further evaluated as a treatment option in the phase III EMBRACA trial, which has completed enrollment and is estimated to complete in December 2019.
TRITON3 clinical trial
Men with metastatic prostate cancer often initially receive androgen therapy, but their disease almost always progresses. PARP inhibitors have been shown to be clinically beneficial for a small group of men with a BRCA1, 2 or ATM mutation who have metastatic prostate cancer. Currently, the PARP inhibitor rucaparib is approved in the U.S. for treatment of ovarian cancer patients who have a BRCA1 or 2 mutation and who have received 2 or more chemotherapies. The ongoing TRITON3 trial is investigating rucaparib versus physicians’ choice of therapy as a treatment option in BRCA or ATM mutation carriers who have metastatic prostate cancer. The estimated completion date is April 2022.
Immunotherapy, a treatment that harnesses one’s own immune system to fight disease, has shown therapeutic promise in several cancers, including breast cancer. Furthermore, response rates have increased when immunotherapy is combined with chemotherapy.
I-SPY 2 clinical trial
Results were presented from the phase II I-SPY 2 trial evaluating pembrolizumab, an immunotherapy in combination with standard therapy (paclitaxel followed by doxorubicin and cyclophosphamide) as a neoadjuvant (before the main treatment) treatment for patients with locally advanced TNBC or hormone receptor–positive/HER2-negative breast cancer. The results showed that adding pembrolizumab increased the complete response rate nearly threefold (60% vs 20%) in patients with TNBC and in patients with hormone receptor–positive/HER2-negative breast cancer (34% vs 13%) compared to standard therapy. Laura J. Esserman, MD, MBA, Professor of Surgery and Radiology and Director of the Carol Franc Buck Breast Care Center at UCSF Helen Diller Family Comprehensive Cancer Center, and the principal investigator for the I-SPY trials said, “The regimen indicates a new and important treatment pathway and gives us well-grounded hope for new options for patients with these aggressive breast cancers—and that’s potentially very good news.”
Two other ongoing clinical trials that were described are also looking at combining immunotherapy and chemotherapy for patients with TNBC. One is a phase II clinical trial that is combining pembrolizumab and paclitaxel for patients with metastatic TNBC breast cancer who have received 2 or more lines of therapy. The other study is looking at whether a onetime treatment with cyclophosphamide, a cytotoxic drug, given prior to pembrolizumab immunotherapy will improve progression free survival for patients with advanced TNBC. Both of these studies are expected to conclude by the end of 2018.
Early results from a prospective study of pancreastic cancer patients suggests that more genes than previously thought likely increase risk for this disease. Findings were presented on the first 239 individuals enrolled in a study (to be completed when 300 pancreatic cancer patients have been evaluated) that is designed to identify which patients have inherited mutations in cancer-predisposing genes. The researchers used a gene panel test that looked at 32 genes previously assicated with inherited mutations that increase cancer risk.
Of the 239 individuals with pancreatic cancer, 11% had an inherited mutation in a gene known to increase risk of pancreastic cancer, including ATM, BRCA1, BRCA2, STK11, and CDKN2A. The results also revealed that 4% of patients had inherited a mutation in BARD1, NF1, RAD50, and CHEK2 — genes that are not currently considered to increase risk of pancreatic cancer. Of these, 9 patients had inherited mutations in CHEK2. In addition, though a significant portion of the patients met hereditary cancer testing criteria defined by the American College of Gastroenterology and the National Comprehensive Cancer Network, the researchers identified six individuals with inherited mutations in cancer genes that did not meet criteria for genetic testing. These results indicate that current guidelines should be updated so that genetic testing and the genes that are tested reflect the increasing number of genes that increase pancreatic cancer risk.
The preliminary results of this study (the remaining patients will undergo genetic testing over the next few months) suggest that a portion of pancreatic cancers involve the same sorts of inherited mutations that would prompt increased screening if found in individuals with breast or ovarian cancer. The patients involved in the study hope that the results will raise awareness about pancreatic cancer patients who have inherited mutations. However, questions remain about screening options for these patients, particularly since inherited mutations in these genes increase cancer risk in other organs (i.e. breast, ovary, prostate, etc.).
Results of a study presented indicate that pregnancy does not appear to increase the chance that breast cancer will recur in young breast cancer survivors. More than 1,200 breast cancer survivors were followed, on average, for 10 years. This research showed that those who became pregnant did not have any higher risk of cancer recurrence or death compared to those who did not become pregnant. This was true even if the women were initially diagnosed with estrogen receptor (ER)-positive tumors. These new findings may help dispel long-held fears that pregnancy could increase the chance of breast cancer's return. However, the researchers pointed out that women with ER-positive cancer will likely need to interrupt any post-surgery (adjuvant) hormone therapy if they are trying to get pregnant. This hormone therapy is used to help prevent recurrence; it is usually recommended that ER+ breast cancer survivors take hormone therapy for at least five years, and in some cases up to 10 years.