New Standard Regimen Proposed For Recurrent Ovarian Cancer

Author: By Laura Cowen, medwireNews Reporter 

medwireNews: A treatment regimen containing bevacizumab, carboplatin and pegylated liposomal doxorubicin significantly delays disease progression and death relative to bevacizumab, carboplatin and gemcitabine in women with recurrent ovarian cancer, phase III study data show. 

“These results suggest that carboplatin–pegylated liposomal doxorubicin–bevacizumab is the new standard regimen for patients with recurrent ovarian cancer suitable for platinum-based and antiangiogenic treatment”, write Jacobus Pfisterer, from the Gynecologic Oncology Center in Kiel, Germany, and co-authors in The Lancet Oncology. 

Their multicentre study included 682 women with epithelial ovarian, primary peritoneal or fallopian tube carcinoma that had recurred more than 6 months after first-line platinum-based chemotherapy. 

In all, 345 patients were randomly assigned to receive the experimental treatment regimen consisting of bevacizumab (10 mg/kg, days 1 and 15), carboplatin (area under the concentration curve [AUC] 5, day 1) and pegylated liposomal doxorubicin (30 mg/m2, day 1) every 4 weeks. 

A further 337 patients were instead given a standard 3-weekly regimen of bevacizumab (15 mg/kg, day 1), carboplatin (AUC 4, day 1) and gemcitabine (1000 mg/m2, days 1 and 8).  

Both regimens were given for six cycles, followed by maintenance bevacizumab (15 mg/kg every 3 weeks) until disease progression or unacceptable toxicity. 

After a median 12.4 and 11.3 months of follow-up in the experimental and standard treatment groups, respectively, the risk of disease progression or death was a significant 19% lower with the experimental regimen than with the standard one, with median progression-free survival (PFS) times of 13.3 and 11.6 months, respectively. 

The risk of death was also a significant 19% lower with the experimental versus standard regimen after a median follow-up of 27.8 and 25.5 months, respectively. The median overall survival was 31.9 and 27.8 months, respectively. 

“[T]hus, although some might question the clinical meaningfulness of a 3-month median progression-free survival advantage, prolongation of overall survival represents the ultimate goal of treatment and a 4-month improvement in the recurrent setting is clinically meaningful”, Jacobus Pfisterer et al remark, adding that they did not detect any “clinically relevant differences in quality of life” between the arms. 

The researchers also note that the PFS advantage associated with the experimental treatment persisted in the subgroup of patients with previous antiangiogenic treatment, at a median of 11.3 months versus 10.1 months among those who received the standard treatment, and a corresponding hazard ratio of 0.73.  

There were no unexpected adverse events (AEs) with either treatment. At least one grade 3 or higher AE occurred in the majority of patients in both the experimental (75%) and standard (81%) treatment groups, most commonly hypertension (27 vs 20%) and neutropenia (12 vs 22%). 

There was one treatment-related death from a large intestine perforation in the experimental group, one due to osmotic demyelination syndrome in the standard group and one due to intracranial haemorrhage, also in the standard group. 

In an accompanying comment, Richard Penson, from Massachusetts General Hospital in Boston, USA, says that while the investigators refer to carboplatin–pegylated liposomal doxorubicin–bevacizumab as a new standard treatment option, he believes the findings “merit a more emphatic conclusion: that carboplatin–pegylated liposomal doxorubicin–bevacizumab should be the new standard of care, and clinicians need good reasons not to use it.” 

He adds: “Platinum-sensitive recurrent ovarian cancer is an increasingly crowded arena for clinical research with PARP inhibitors, DNA damage response-targeted therapy, antiangiogenics, immunotherapeutics, antibody–drug conjugates, and novel molecules. 

“The results of this trial suggest that carboplatin–pegylated liposomal doxorubicin–bevacizumab is the new back-bone, and studies such as PAOLA-1, with olaparib, show the additive benefit of PARP inhibitors and antiangiogenics in combination.” 

References 

Pfisterer J, Shannon CM, Baumann K, et al. Bevacizumab and platinum-based combinations for recurrent ovarian cancer: a randomised, open-label, phase 3 trial. Lancet Oncol; Advance online publication 16 April 2020. DOI: https://doi.org/10.1016/S1470-2045(20)30142-X

Penson RT. Platinum-sensitive ovarian cancer: liminal advances. Lancet Oncol; Advance online publication 16 April 2020. DOI: https://doi.org/10.1016/S1470-2045(20)30178-9