Highlights from the June 2016 American Society of Clinical Oncology (ASCO) Annual Meeting

(June 20, 2016) Highlights from the June 2016 American Society of Clinical Oncology (ASCO) Annual Meeting by Susan Leighton, Ovarian Cancer Survivor and Research Advocate

Since the first time I attended ASCO I have seen the number of abstracts presented about ovarian cancer increase significantly as understanding of the disease has expanded. No longer do we hear the one size fits all approach to ovarian cancer; ovarian cancer is a heterogeneous disease with several subtypes. It has become quite clear that low-grade and high-grade ovarian cancer present differently and respond to treatment differently. A potential therapeutic target may be present in high-grade serous ovarian cancer but not in clear cell ovarian cancer. Researchers are focusing on these differences and similarities. A few years ago the push was for one screening test, one silver bullet. Now we know that the questions are far more complex.

Another significant development has been the increasing focus on survivorship and quality of life. Recognizing that patients are living longer, the questions of how best to care for this population was the topic of great discussion. Survivors need to be advocates in their own care asking about potential long-term side effects of treatment, recommended surveillance and follow-up when treatment is completed, as well as other quality of life issues. Additionally survivors should consider lending their voice to the larger discussion. The patient perspective will continue to move the field of survivorship forward.

Clinical trial design and ways to improve patient accrual continue to take center stage. The patient voice is critical to understanding these issues. This was very apparent in a meeting of patient advocates and FDA patient representatives during which FDA officials asked for our input on what patients want and need from clinical trials. The take-away message is get involved and bring the patient voice to the table.

Intraperitoneal chemotherapy for Ovarian Cancer: Trials and Tribulations: Following the presentation of GOG252, a phase III trial, at the SGO annual meeting, many questions lingered and the presenters of this session attempted to offer some clarity. GOG252 compared intraperitoneal and intravenous chemotherapy. There were three trial arms, and patients in all three arms received IV bevacizumab. Arm 1: IV carboplatin AUC (area under the curve) 6/IV weekly paclitaxel at 80 mg/m2. Arm 2: IP carboplatin AUC 6/IV weekly paclitaxel at 80 mg/m2. Arm 3: IV paclitaxel at 135 mg/m2 on day 1/IP cisplatin at 75 mg/m2 on day 8.

Dr. Helen Mackay of the Princess Margaret Hospital in Canada noted that progression free survival (PFS) was similar for all three study arms. Although, IP chemo studied in GOG 172 had shown amazing results of 60.4 months PFS, in GOG 252 PFS was 33.8 months. Why the marked difference? Some questions include:
• All patients in GOG252 underwent 6-month CT scans (not done in GOG 172). Was PFS influenced by the results of the scans?
• Did dose reduction of paclitaxel and cisplatin and patient cross over from the IP arm to the IV arm confound the results?
• Did the introduction of bevacizumab negate the IP results seen previously?
Other panel participants including Dr. Charlie Gourley of the University of Edinburgh agreed with the need for further clarification of these results while emphasizing that previous trials (GOG 104, 114, and 172) resulted in longer PFS using intraperitoneal compared to intravenous chemotherapy and stating that BRCA1/2 patients could benefit from the use of IP. All agreed that there are unresolved issues regarding the use of IP chemotherapy and much work remains to better understand the microenvironment and biology of ovarian cancer and the role of IP chemotherapy in treatment.

Overall survival (OS) in patients with platinum-sensitive relapsed serous ovarian cancer (PSR SOC) receiving olaparib maintenance monotherapy: An interim analysis.

Dr. Jonathan Ledermann from the United Kingdom summarized findings to date of a phase II trial that found patients who received maintenance olaparib after responding to platinum therapy demonstrated an overall survival advantage. BRCA mutation and platinum sensitive relapsed serous ovarian cancer showed a significant progression free survival benefit from olaparib maintenance monotherapy, both with BRCA germline and somatic mutations.

Hormonal maintenance therapy for women with low-grade serous carcinoma of the ovary or peritoneum.
Dr. David Gershenson of MD Anderson explained that while low-grade serous carcinoma (LGSC) has been shown to be relatively chemoresistant, postoperative platinum-based chemotherapy remains the standard of care for women newly diagnosed with this subtype. Newly diagnosed patients with stage II-IV LGSC who had undergone treatment primary treatment with cytoreductive surgery followed by platinum-based chemotherapy and at least two years of follow-up who had not recurred were randomized to surveillance or hormonal maintenance therapy (letrozole, tamoxifen, anastrozole or leuprolide acetate). Women who received HMT had a statistically significant improvement in progression free survival compared to women in the surveillance arm of the study (34 months PFS versus 29.9 months).

Multicenter phase II study of intraperitoneal carboplatin plus intravenous dose-dense paclitaxel in patients with suboptimally debulked epithelial ovarian or primary peritoneal carcinoma.

Dr. Kosei Hasegawa of Japan reported on a multicenter phase II prospective trial conducted to evaluate the efficacy and safety of intraperitoneal carboplatin in combination with dose-dense paclitaxel and carboplatin (ddTCip) in patients with stage II-IV ovarian or primary peritoneal carcinoma suboptimally debulked at primary cytoreductive surgery. The trial results suggest that frontline chemotherapy with this regimen is safe and effective for those who are suboptimally debulked at initial surgery. A phase III randomized trial comparing ddTCip and ddTC (dose dense paclitaxel and carboplatin) is currently ongoing.

The MITO8 phase III international multicenter randomized study testing the effect on survival of prolonging platinum-free interval (PFI) in patients with ovarian cancer recurring between 6 and 12 months after previous platinum-based chemotherapy: A collaboration of MITO, MANGO, AGO, BCOG, ENGOT, and GCIG.

This study addressed the question of whether introducing a non-platinum based chemotherapy and prolonging the platinum-free interval would improve sensitivity to platinum. The trial concluded that prolonging the platinum-free interval by introducing a non-platinum based agent does not improve and even worsens efficacy outcomes in patients with partially platinum sensitive recurrent ovarian cancer.

Baseline quality of life (QOL) as a predictor of stopping chemotherapy early, and of overall survival, in platinum-resistant/refractory ovarian cancer (PRROC); The GCIC symptom benefit study (SBS).
Dr. Felicia Roncolato, of St. George Hospital in Sydney Australia, reported that assessing baseline quality of life in women with PRR-ROC might help identify which patients are unlikely to benefit from palliative chemotherapy. The SBS showed that Global Health status, physical function, role function and abdominal/GI symptoms were independent predictors for overall survival, and were significantly associated with stopping chemotherapy early. The worse the symptoms, the shorter the survival.

Association of ovarian cancer risk with mutations detected by multiple-gene germline sequencing in 96,561 women.

Dr. Alison Kurlan of Stanford presented the results of this study to attempt to assess ovarian cancer risk for genes on one commercially available panel of 25 genes. Multivariable regression analysis was used to examine the association between pathogenic/suspected pathogenic mutations and a personal history of ovarian cancer. Personal histories were also collected. Among nearly 100,000 women, multiple-gene sequencing detected ovarian cancer associated mutations in 11 genes.

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