open access: Olaparib Maintenance Therapy in Platinum-Sensitive Relapsed Ovarian Cancer — NEJM

Olaparib Maintenance Therapy in Platinum-Sensitive Relapsed Ovarian Cancer — NEJM

......"We evaluated the efficacy of olaparib monotherapy as maintenance treatment in patients with platinum-sensitive, relapsed, high-grade serous ovarian cancer who had had a response to their most recent platinum-based chemotherapy......"

In conclusion, the results from this randomized, phase 2 study show that maintenance treatment with olaparib was associated with a significant improvement in progression-free survival among patients with platinum-sensitive, relapsed, high-grade serous ovarian cancer. However, at the interim analysis, this did not translate into an overall survival benefit. As of this writing, 21% of the patients were still receiving olaparib (and 3% were still receiving placebo), which indicates that the disease is controlled for a prolonged period in some patients.

(Pre-)Clinical Pharmacology and Activity of Pazopanib, a Novel Multikinase Angiogenesis Inhibitor

"In a phase I trial, a generally well-tolerated dose was identified at which the majority of patients achieved pazopanib plasma concentrations above the concentration required for maximal in vivo inhibition of VEGFR-2 phosphorylation in preclinical models.
Administered as monotherapy, evidence of antitumor activity was observed in phase II studies in several tumor types, including soft tissue sarcoma, renal cell cancer (RCC), ovarian cancer, and non-small cell lung cancer.
Recently, the U.S. Food and Drug Administration granted approval for treatment with pazopanib in patients with RCC based on the longer progression-free survival time observed with this agent in a placebo-controlled, randomized trial.
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"Furthermore, preliminary data from a small phase II study in women with progressive, platinum-pretreated ovarian cancer showed a cancer antigen 125 response (defined as a confirmed decrease 50% from baseline) in 11 (31%) patients, with a median duration of response of 113 days.*>"

(*Annals of Oncology 19 (Supplement 8): viii211–viii216, 2008
doi:10.1093/annonc/mdn512:
PAZOPANIB (GW786034) IS ACTIVE IN WOMEN WITH
ADVANCED EPITHELIAL OVARIAN, FALLOPIAN TUBE AND
PERITONEAL CANCERS: RESULTS OF A PHASE II STUDY
M. Friedlander1, K.C. Hancock2, B. Benigno3, D. Rischin4, M. Messing5,
C.A. Stringer6, J.P. Hodge7, B. Ma7, G. Matthys7, J.J. Lager7
1Oncology Day Center, Prince of Wales Hospital, Randwick, Sydney/
AUSTRALIA, 2Oncology, Texas Oncology, Fort Worth/UNITED STATES OF
AMERICA, 3Oncology, SE Gynecologic Oncology, Atlanta/UNITED STATES OF
AMERICA, 4Oncology, Mercy Hospital for Women, Melbourne/AUSTRALIA,
5Oncology, Texas Oncology, Bedford/UNITED STATES OF AMERICA,
6Oncology, Texas Oncology, Dallas/UNITED STATES OF AMERICA, 7Scientific
Communications, GlaxoSmithKline, Research Triangle Park/UNITED STATES
OF AMERICA )

" Putting pazopanib into perspective and comparing it with other VEGFR TKIs that have been approved for a longer time are difficult and have to be done on the basis of indirect comparisons, given the lack of data from comparative trials among the several treatment options."

Platinum-based adjuvant chemotherapy for early-stage ovarian cancer (abstract)

Conclusions
Combination therapy is administered more often than carboplatin; especially in those with younger age, better PS and nonmucinous histology. Recurrence and death rates were similar with both treatments. Well-designed trials are needed to identify the optimum chemotherapy regimen in this group.