A novel topoisomerase-I inhibitor designated NKTR-102 demonstrated clinically significant activity as a single agent in patients with heavily pretreated ovarian cancer who failed prior pegylated liposomal doxorubicin (PLD), according to results of a phase II trial presented at the 2011 ASCO meeting in June.
“NKTR-102 exhibits an exceptionally high response rate and long median survival compared to what would be expected in this group of heavily pretreated women with platinum-resistant and refractory ovarian cancer,” said presenting author Agustin Garcia, MD, associate professor of clinical medicine at USC Norris Comprehensive Cancer Center in Los Angeles, California.
Initial response rates to platinum-based therapy are achieved in up to 80% of women with ovarian cancer, but most patients will recur. Over time, nearly all ovarian cancers will become resistant or refractory to platinum-based therapy. Treatment options after relapse are limited and long-term survival is poor. There are currently no good treatment options for women who progress on PLD, Garcia explained.
The phase II study was an international, multicenter, open-label, randomized 2-stage study to evaluate NKTR-102 given either every 14 days or every 21 days. Investigators randomized 71 women to treatment with either the every-14-day regimen or the every-21-day regimen. Women were either platinum-resistant or platinum-refractory with a platinum-free interval of at least 6 months. Forty-six percent (33 patients) had failed prior treatment with PLD. Women who enrolled in the study had a median of 4 prior treatments; 15% had prior bevacizumab; 58% had prior gemcitabine; and 100% had prior taxane.
The analysis presented at ASCO focused on the 33 patients who progressed on PLD. Confirmed objective response rates using RECIST criteria were 19% for the q14day regimen and 21% for the q21day regimen. Confirmed objective response rates using GCIG criteria were 38% and 35% for the 2 regimens, respectively.
Median progression-free survival (PFS) for the 33 patients previously treated with PLD was 54 months and median overall survival (OS) was 13.9 months. Median duration of confirmed response was 4.2 months in the q14day schedule and 4.4 months in the q21day schedule.
NKTR-102 was generally well tolerated in the subset of women previously treated with PLD, especially those on the q21day schedule. The most common grades 3 and 4 adverse events were diarrhea (31% for the q14day regimen and 18% for the q21day regimen), hypokalemia (31% and 0%, respectively), and nausea (31% and 6%, respectively). Most events were grade 3 in severity
Garcia AA, Vergote IB, Micha JP, et al. The role of NKTR- 102 in women with platinum resistant/refractory ovarian cancer and failure on pegylated liposomal doxorubicin. J Clin Oncol. 2011;29(suppl; abstr 5047).