Efficacy and Safety of Bevacizumab-Containing Therapy in Newly Diagnosed Ovarian Cancer: (35 countries)

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 Hypertension also seemed to be more common in ROSiA than in ICON7  or GOG-0218.

 Overall survival results are immature with events in only
23% of patients. Unfortunately, further long-term follow-up is
not planned within the framework of the study, as the ROSiA
safety study was designed with PFS as the primary efficacy
outcome rather than OS.
In summary, results from this large multinational
frontline study in ovarian cancer indicate that extended
bevacizumab-containing therapy is both tolerable and feasible.
The single-arm study design does not allow us to draw definitive
conclusions on the impact of treatment duration on efficacy;
however, the median PFS of 25.5 months is the longest
reported to date.

 Abstract

Objective: The aim of this study was to assess the safety and efficacy of extending bevacizumab therapy beyond 15 months in nonprogressive ovarian cancer.

Patients and Methods: In this multinational prospective single-arm study (ClinicalTrials.gov NCT01239732), eligible patients had International Federation of Gynecology and Obstetrics stage IIB to IV or grade 3 stage I to IIA ovarian cancer without clinical signs or symptoms of gastrointestinal obstruction or history of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the preceding 6 months. Prior neoadjuvant chemotherapy was permitted. After debulking surgery, patients received bevacizumab 15 (or 7.5) mg/kg every 3 weeks (q3w) with 4 to 8 cycles of paclitaxel (investigator's choice of 175 mg/m2 q3w or 80 mg/m2 weekly) plus carboplatin AUC 5 to 6 q3w. Single-agent bevacizumab was continued until progression or for up to 24 months. The primary end point was safety.

Results: Between December 2010 and May 2012, 1021 patients from 35 countries began study treatment. Bevacizumab was administered at 15 mg/kg in 89% of patients and for more than 15 months in 53%. Median follow-up duration was 32 months (range, 1-50 months). The most common all-grade adverse events were hypertension (55% of patients), neutropenia (49%), and alopecia (43%). The most common grade 3 or higher-grade adverse events were neutropenia (27%) and hypertension (25%). Bevacizumab was discontinued because of proteinuria in 5% of patients and hypertension in 3%. Median progression-free survival (PFS) was 25.5 months (95% confidence interval, 23.7-27.6 months).

Conclusion: Extended bevacizumab demonstrated increased incidences of proteinuria and hypertension compared with 12 or 15 months of bevacizumab in previous trials, but these rarely led to bevacizumab discontinuation. Median PFS is the longest reported for frontline bevacizumab-containing therapy. The longer bevacizumab duration beyond 15 months in this study may improve PFS without substantially compromising safety.

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              Study Design and Patients
Generally, eligibility criteria were designed to recruit a
patient population similar to that enrolled in ICON7. Patients
had to be aged 18 years or older with Eastern Cooperative
Oncology Group performance status 0 to 2. Eligible patients
had histologically confirmed epithelial ovarian carcinoma,
fallopian tube carcinoma, or primary peritoneal carcinoma of
International Federation of Gynecology and Obstetrics
(FIGO) stage IIB to IV (any grade) or stage I to IIA (grade 3),
or clear cell carcinoma, or carcinosarcoma. Patients should
have already undergone maximal surgical debulking unless
they had inoperable stage III or IV disease. Unlike ICON7,
patients could be enrolled after neoadjuvant chemotherapy
and interval debulking surgery, with bevacizumab initiated
after surgery.

Histologic classification†
Serous 750 (73.5)
Endometrioid 90 (8.8)
Clear cell 68 (6.7)
Mucinous 23 (2.3)
Mixed 65 (6.4)
Adenocarcinoma NOS 88 (8.6)
Other 48 (4.7)