Androgen Receptor Inhibitor Active in Endometrial Cancer
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More than 70% of women with advanced or recurrent endometrial cancer responded to treatment that included the androgen receptor inhibitor (ARI) enzalutamide (Xtandi), a small phase II study showed.

Overall, 25 of 35 (71%) evaluable patients had objective responses when they received enzalutamide plus standard chemotherapy, including nine complete responses. Five other patients had stable disease. Additionally, 29 of 35 (83%) patients remained progression free at 6 months. Median progression-free survival (PFS) was 11.47 months for 49 treated patients, increasing to 14.42 months in the response-evaluable subgroup.

Toxicity was consistent with known side effects of chemotherapy, and no toxicities unique to enzalutamide were observed, reported Shannon N. Westin, MD, of the MD Anderson Cancer Center in Houston, at a late-breaking abstract session of the Society of Gynecologic Oncology virtual meeting.

“The combination of enzalutamide and paclitaxel and carboplatin yielded promising clinical outcomes in patients with chemo-naïve advanced and recurrent endometrioid endometrial cancer,” said Westin. “The combination was tolerable, and I’m excited to report that our translational analyses are now ongoing, looking at predictors of this important therapy.”

The rationale for evaluating adding an ARI to chemotherapy originated in evidence that AR is overexpressed in more than 90% of endometrioid endometrial cancers (EECs). Additionally, androgens are associated with endometrial cancer risk, AR protein expression is associated with endometrial cancer survival, and androgen-dependent signaling is associated with growth inhibition in endometrial cancer cell lines via cyclin D1 and KRAS protein expression.

Eligibility criteria for the phase II trial included untreated stage III/IV or recurrent EECs with measurable disease. Documentation of AR expression was not required.

Apatinib for Platinum-Resistant Ovarian Cancer

Adding the angiogenesis inhibitor apatinib (Aitan in China) to chemotherapy led to statistically significant improvement in PFS for platinum-resistant ovarian cancer, a randomized trial showed.

Median PFS increased from 3.3 months with pegylated liposomal doxorubicin (PLD) alone to 5.8 months with the addition of apatinib, representing a 56% reduction in the hazard ratio for disease progression or death (95% CI 0.28-0.71, P=0.0005). Among 129 patients with evaluable disease, the apatinib arm had an objective response rate of 43.1% as compared with 10.9% for PLD alone (P<0.0001).

After a median follow-up of 8.5 months, the disease control rates (response plus stable disease) were 84.6% with apatinib and 57.8% with PLD alone (P=0.0007). In 100 evaluable patients, 43 of 49 (87.8%) in the apatinib arm had some degree of tumor reduction as compared with 20 of 51 (39.2%) patients in the PLD group.

“Apatinib plus PLD was generally well tolerated, with manageable toxicities; no unexpected safety signals were identified beyond the established safety profile of each single agent,” said Tiantian Wang, MD, of the National Cancer Center and Peking Union Medical College in Beijing. “A randomized phase III trial is planned in platinum-resistant recurrent ovarian cancer.”

Investigators treated 146 randomized patients. Eligible patients had nonmucinous disease type and progression during or within 6 months after discontinuing any prior line of platinum-based chemotherapy. The trial’s primary endpoint was PFS.

PD-1 Inhibitor Active in Vulvar Cancer

Pembrolizumab (Keytruda) had durable activity in a portion of patients with recurrent or metastatic vulvar squamous cell carcinoma, results of a large phase I basket study showed.

Single-agent therapy led to an overall response rate of 10.9%. Patients with PD-L1-positive tumors (combined positive score ≥1) had a response rate of 9.5% (eight of 84), and two of seven patients with PD-L1-negative tumors also responded. Though infrequent, responses tended to be durable (median duration of 20.4 months).

The cohort had a median PFS of 2.1 months and median overall survival (OS) of 6.2 months. PFS at 6, 12, and 24 months was 19.8%, 9.9%, 6.4%, and OS at the same time points was 50.5%, 34.7%, and 14.0%, respectively.

Overall, the treatment was well tolerated. The most common treatment-related adverse events (TRAEs, all grades) were nausea (7.9%); diarrhea and hypothyroidism (6.9% each); asthenia, decreased appetite, fatigue, and pruritus (5.9%); hyperthyroidism and rash (5.0%). The most common grade ≥3 TRAEs were diarrhea, fatigue, and rash, occurring in about 1% of patients.

“This is a large cohort of vulvar disease, with no standard-of-care systemic therapy; yet, 10.9% of patients responded to pembrolizumab monotherapy,” said Ronnie Shapira Frommer, MD, of Sheba Medical Center in Ramat Gan, Israel. “Both PD-L1-positive and negative responses were durable. A meaningful subset of patients experienced prolonged overall survival. There were no new safety issues detected in this cohort.”

  • Charles Bankhead is senior editor for oncology and also covers urology, dermatology, and ophthalmology. He joined MedPage Today in 2007. Follow

Disclosures

The trial by Westin’s group was supported by the MD Anderson Cancer Center/NCI. Westin disclosed relevant relationships with AstraZeneca, ArQule, Bayer, Bio-Path, Clovis Oncology, Cotinga Pharmaceuticals, GlaxoSmithKline/Tesaro, Novartis, Roche/Genentech, Agenus, Circulogene, Eisai, Merck, Pfizer, and Zentalis.

The study by Wang’s group was supported by the National Key Research & Development Program of China, Jiangsu Hengrui Pharmaceuticals, and CSPC Pharmaceutical Group. Wang disclosed no relevant relationships with industry.

The study by Frommer’s group was supported by Merck. Frommer disclosed relevant relationships with Merck Sharp & Dohme, Bristol-Myers Squibb, AstraZeneca, Novartis, Roche, Clovis Oncology, and VBL Therapeutics.

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