Have We Given up on a Cure for Ovarian Cancer?

Abstract

A Countercurrents Series a with S.A. Narod md* In December 2014, on the force Web site, executive director Sue Friedman, heralded a game-changing holiday gift for people with BRCA mutations: "Today is a landmark for the hboc [hereditary breast and ovarian cancer] community" 1 . In an accompanying article 2 , Lisa Rezende wrote about the U.S. Food and Drug Administration (fda) decision to approve olaparib for the treatment of recurrent ovarian cancer in women with a BRCA1 or BRCA2 mutation:The fda has approved Lynparza [AstraZeneca, Wilmington, DE, U.S.A.] (also known as olaparib) to treat ovarian, fallopian tube, and primary peritoneal cancer in women who carry mutations in BRCA1 or BRCA2, and who have received three or more chemotherapy treatments. Lynparza is the first parp [poly adp ribose polymerase] inhibitor to be approved, and the first drug that requires patients to undergo testing for a BRCA mutation before they can receive it.While the approval of Lynparza is a great first step in treating cancers in BRCA mutation carriers, much work remains. Lynparza has been approved for use in ovarian cancer patients who received three prior chemotherapies, making it what is known as a "fourth line" drug. More research is still needed to determine if parp inhibitors will work in other settings. Ongoing clinical trials are enrolling patients with cancer to answer these questions."Much work remains" is an understatement-akin to saying that recurrent ovarian cancer is "difficult to treat." Notable in Rezende's words, and in statements elsewhere in the press, is that that no one says exactly how good olaparib actually is. What does Rezende mean when she says that a parp inhibitor "works"-in the fourth-line ovarian cancer setting or in any other setting?Olaparib is approved only for women with recurrent cancers who have received three or more lines of chemotherapy: that is, for those unfortunate women who are already destined to die of their cancer. In no study that I have seen does olaparib prevent women from dying of cancer or even delay their death. It has been associated with improvements in progression-free survival: that is, when given either alone 3 or in combination with cisplatin or carboplatin 4 to women who responded to platinum, olaparib delayed cancer recurrence.In the first study 3 , in women with a BRCA mutation and platinum-sensitive recurrent ovarian cancer, olaparib prolonged the time to recurrence to 11.2 months from 4.3 months, but the median time to death was a stolid 34.9 months in the olaparib group compared with 31.9 months in the control group (p = 0.19). In the second study 4 , in an overall patient population, time to progression was 12.2 months in the chemotherapy plus olaparib group and 9.6 months in the chemotherapy-alone group. The difference was greater in the BRCA-positive subgroup, but that group was small (41 patients), and compared with women who did not take olaparib, mutation-positive women who took olaparib did not experience an extended time to death (hazard ratio: 1.28; 95% confid...

Comparative Study of Multicellular Tumor Spheroid Formation Methods and Implications for Drug Screening

“…Only two ovarian cancer drugs have been approved by the U.S Food and Drug Administration (FDA) in the past 10 years. 66 Therefore, there is a pressing need to more accurately model ovarian cancer in vitro to better identify effective treatments. In this study, OCAS from patient-derived samples were compared to an established ovarian cancer cell line formed in MCTS in polyNIPAAM.…”

“…Finally, we compared our polyNIPAAM MCTS to patient-derived ovarian cancer ascites, because drug approval for ovarian cancer therapy has begun to stagnate. Only two ovarian cancer drugs have been approved by the U.S Food and Drug Administration (FDA) in the past 10 years . Therefore, there is a pressing need to more accurately model ovarian cancer in vitro to better identify effective treatments.…”

Why have ovarian cancer mortality rates declined? Part II. Case-fatality

“…Maintenance therapy refers to the administration of treatment for extended periods of time or until the time of relapse, in patients with residual macroscopic disease after surgery or in patients with recurrent ovarian cancer [18]. The goal of maintenance therapy is typically to improve progression-free survival, symptom-free survival or overall survival, but not necessarily cure [19]. In recent years, progression-free survival has replaced overall survival as the primary endpoint of ovarian cancer clinical trials.…”