Carboplatin–Paclitaxel Recommended For Elderly Advanced Ovarian Cancer Patients

Author: By Lynda Williams, Senior medwireNews Reporter 

medwireNews: Findings from the Elderly Women With Ovarian Cancer (EWOC)-1 trial demonstrate significant progression-free survival (PFS) and overall survival (OS) benefits with use of paclitaxel alongside carboplatin in newly diagnosed patients with a high Geriatric Vulnerability Score. 

“Contrary to the current practice of considering single-agent carboplatin in frail patients, these results suggest that even vulnerable older women with newly diagnosed ovarian cancer should be offered carboplatin–paclitaxel combination therapy”, say Claire Falandry, from Centre Hospitalier Lyon Sud in France, and co-investigators.  

The study included 120 women aged a median 80 years with FIGO stage III–IV epithelial ovarian, fallopian tube or primary peritoneal cancer, with or without successful debulking surgery.  

All of these patients had a Geriatric Vulnerability Score (GVS) of 3 or higher calculated from daily living activity scores, albuminemia and lymphopenia, and indicative of “a particularly vulnerable population with significantly worse OS, treatment completion, and toxic effects”, the authors explain in JAMA Oncology. 

The primary endpoint of treatment feasibility, defined as completion of six cycles without disease progression, adverse events (AEs) leading to discontinuation, hospitalisation, prolonged dose delays or reductions, or death, was achieved by 65% of the 40 patients who were randomly assigned to receive the standard regimen of carboplatin AUC 5 mg/mL per min plus paclitaxel 175 mg/m2 every 3 weeks. 

Similarly, 60% of the 40 women given weekly carboplatin AUC 2 mg/mL per min plus paclitaxel 60 mg/m2 on days 1, 8 and 15 of each 4-week cycle achieved this endpoint. 

But this rate was just 48% for the 40 patients given single-agent carboplatin, at a dose of either AUC 5 or 6 mg/mL per minute every 3 weeks, the investigators say. 

The standard and weekly combination regimen patients each received a median of 6.0 cycles versus 4.5 cycles for the carboplatin monotherapy patients. Although the rate of early discontinuation for toxicity was comparable in the three groups (20, 23 and 15%, respectively), patients given the combination regimens were less likely to discontinue treatment early because of lack of efficacy than those given only carboplatin (8, 5 and 30%, respectively). 

Median PFS was significantly longer with standard combination treatment than single-agent carboplatin at 12.5 versus 4.8 months and a hazard ratio (HR) for progression or death of 2.51. The corresponding values for OS were unreached versus 7.4 months and a significant HR for death of 2.79.  

 
The median PFS and OS durations for the weekly combination arm were 8.3 and 17.3 months, respectively. 

And there were similar survival patterns found with the different regimens when assessing patients with a GVS score of 3 and in more vulnerable patients with a GVS score of 4 or 5, the team notes. 

The researchers add that treatment-related AEs were less common with the chemotherapy combination given every 3 weeks than the weekly combination regimen or the single-agent carboplatin option, affecting 43%, 58% and 58% of patients, respectively. 

Patients given the weekly regimen were more likely to experience grade 3 or more severe neutropenia than those given only carboplatin, and low-grade gastrointestinal toxicity, neuropathy and alopecia were more common with either of the combination versus single-agent carboplatin. By contrast, patients given carboplatin alone had a higher rate of grade 3 or more severe thrombocytopenia and anaemia than women given a combination regimen. 

Both of the combination arms had two treatment-related deaths whereas there were no such events in the carboplatin alone arm.  

The EWOC-1 investigators note that the trial was prematurely discontinued on the basis of excessive toxicity in all treatment arms and inferior efficacy of the single-agent carboplatin versus the combination regimens, “although no definitive conclusions about the relative feasibility, efficacy, and safety of the 2 combination regimes could be reached”, they remark. 

While encouraging further research in this patient population, Claire Falandry et al advise: “Management of vulnerable older patients with ovarian cancer should include, from cancer diagnosis, a personalized plan for oncogeriatric care, including both oncologic and geriatric treatment plans. 

“If the oncologic plan considers the survival advantage provided by carboplatin–paclitaxel doublets, the geriatric plan must be prioritized in parallel, given the high toxic effects observed in this population, and should address the major components of the GVS (functionality, malnutrition, mood disorders).”

Reference  

Falandry C, Rousseau F, Mouret-Reynier M-A, et al. Efficacy and safety of first-line single-agent carboplatin vs carboplatin plus paclitaxel for vulnerable older adult women with ovarian cancer. A randomized clinical trial. JAMA Oncol; Advance online publication 22 April 2021. doi:10.1001/jamaoncol.2021.0696