Adjuvant chemotherapy did not lead to survival improvements vs standard chemoradiotherapy alone in patients with locally advanced cervical cancer and resulted in more severe adverse events, according to OUTBACK trial data.
There was no overall survival improvement seen when adjuvant carboplatin and paclitaxel chemotherapy was given after standard cisplatin-based chemoradiotherapy for unselected locally advanced cervical cancer, according to findings from the OUTBACK trial (NCT01414608).1
Finding showed that at the data cutoff date of April 12, 2021, the median follow-up was 60 months (IQR, 45-65). The 5-year overall survival rate was similar between groups at 72% (95% CI, 67-76) in the adjuvant chemotherapy group and 71% (95% CI, 66-75) in the chemoradiotherapy only group (95% CI, 0.70-1.17; P = .81).
“Giving adjuvant carboplatin and paclitaxel chemotherapy after standard chemoradiation to the pelvis for locally-advanced cervical cancer did not improve the efficacy of treatment or overall survival, but did significantly increase [adverse events] for women,” Linda R. Mileshkin, MD, medical oncologist, Peter MacCallum Cancer Centre, and principal investigator on the study, told Targeted OncologyTM.
The multicenter, open-label, randomized, phase 3 trial was done in 157 hospitals in locations including the United States, Australia, China, Canada, New Zealand, Saudi Arabia, and Singapore.
Patients enrolled in the trial were aged 18 years or older with histologically confirmed squamous cell carcinoma, adenosquamous cell carcinoma, or adenocarcinoma of the cervix, and ECOG performance status 0 of 2, and adequate bone marrow and organ function.
Patients were randomly assigned in a 1:1 ratio to receive standard cisplatin-based chemoradiotherapy at a dose of 40 mg/m2 cisplatin intravenously (IV) once-a-week for 5 weeks, during radiotherapy with 45.0-50.4 Gy external beam radiotherapy which was delivered in fractions of 1.8 Gy to the whole pelvis plus brachytherapy (chemoradiotherapy only group) or to receive standard cisplatin-based chemoradiotherapy followed by adjuvant chemotherapy with 4 cycles of carboplatin and paclitaxel at 155 mg/m2 given via IV infusion on day 1 of the 21 day cycle (adjuvant chemotherapy group).
The primary end point of the trial was overall survival at 5 years. Secondary end points were progression-free survival at 5 years, adverse events (AEs), patterns of disease recurrence, radiation protocol compliance, and quality-of-life for global health status.2
A total of 926 patients were enrolled and randomly assigned between April 15, 2011, and June 26, 2017. There were 461 patients enrolled in the chemoradiotherapy only group and 465 in the adjuvant chemotherapy group, and 919 were eligible and included in the analysis (456 in the chemoradiotherapy only group and 463 in the adjuvant chemotherapy group).1
The median age of patients 46 years (interquartile range [IQR], 37-55 years), 663 (72%) were White, 121 (13%) were Black or African American, 53 (6%) were Asian, 24 (3%) were Aboriginal or Pacific islander, and 57 (6%) were other races.
The PFS rates were similar at 63% vs 61%, respectively, in the adjuvant chemotherapy vs chemoradiotherapy only group. For safety, there was a higher percentage of women experiencing severe AEs within a year of randomization when receiving adjuvant chemotherapy (81%) compared with those given standard chemotherapy (62%).
The most common grade 3-4 AEs included decreased neutrophils in 71 (20%) patients in the adjuvant chemotherapy group vs 34 (8%) patients in the chemoradiotherapy only group, and anemia in 66 (18%) vs 34 (8%). A total of 107 (30%) patients in the adjuvant chemotherapy group vs 98 (22%) in the chemoradiotherapy only group had serious AEs, most commonly due to infectious complications, and there were no treatment-related deaths.
“A recent analysis of the United States National Cancer Database suggested that 1 in 10 patients were receiving multi-agent adjuvant chemotherapy in addition to chemo-radiation with no survival benefit. Concerningly, there was also a lower rate of brachytherapy completion in those treated with adjuvant chemotherapy, which is essential to get local control of the cancer,” added Mileshkin.
Overall, these data confirm that the current best standard treatment for women with locally advanced cervical cancer is chemoradiation alone as the addition of adjuvant chemotherapy did not improve 5-year survival rates and added significant AEs.