Adding adjuvant chemotherapy to standard chemoradiotherapy (CRT) does not improve outcomes in patients with locally advanced cervical cancer, according to research published in The Lancet Oncology.
Adjuvant chemotherapy increased toxicity without improving overall survival (OS) or progression-free survival (PFS), researchers found.
The results come from the open-label, phase 3 OUTBACK study (ClinicalTrials.gov Identifier: NCT01414608), which included 919 patients with locally advanced cervical cancer. The median age of the patients was 46 years. Most patients were White (72%), had an ECOG performance status of 0 (74%), and had squamous cell carcinoma (81%).
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The patients were randomly assigned to receive standard CRT alone (n=456) or CRT followed by adjuvant chemotherapy (n=463). Baseline characteristics were similar between the treatment arms.
CRT consisted of cisplatin given at 40 mg/m² once weekly for 5 weeks, 45.0-50.4 Gy of external beam radiotherapy given in fractions of 1.8 Gy to the whole pelvis, and brachytherapy. Adjuvant chemotherapy consisted of 4 cycles of carboplatin (AUC 5) and paclitaxel (155 mg/m²) given on day 1 of each 21-day cycle.
The median follow-up was 60 months. The 5-year OS rate was 72% in the adjuvant chemotherapy arm and 71% in the CRT-alone arm (hazard ratio [HR], 0.90; 95%, 0.70-1.17; P =.81).
The 3-year PFS rate was 70% in the adjuvant chemotherapy arm and 66% in the CRT-alone arm (HR, 0.86; 95% CI, 0.69-1.08; P =.17). The 5-year PFS rate was 63% and 62%, respectively (HR, 0.86; 95% CI, 0.69-1.08; P =.58).
The rate of grade 3 or higher adverse events (AEs) was 81% in the adjuvant chemotherapy arm and 62% in the CRT-alone arm (P <.0001). Serious AEs occurred in 30% and 22% of patients, respectively.
The most common grade 3-4 AEs (in the adjuvant chemotherapy arm and CRT-alone arm, respectively) were decreased lymphocyte count (58% vs 46%), decreased neutrophil count (20% vs 8%), and anemia (18% vs 8%).
“[A]djuvant carboplatin and paclitaxel following CRT should not be used in this disease setting,” the researchers concluded. “Future studies should select participants with high-risk disease and overcome barriers to adherence with treatment.”
Disclosures: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.
Reference
Mileshkin LR, Moore KN, Barnes EH, et al. Adjuvant chemotherapy following chemoradiotherapy as primary treatment for locally advanced cervical cancer versus chemoradiotherapy alone (OUTBACK): An international, open-label, randomised, phase 3 trial. Lancet Oncol. Published online April 17, 2023. doi:10.1016/S1470-2045(23)00147-X
