Lack of survival benefit with adjuvant chemotherapy in locally advanced cervical cancer

Chemoradiotherapy is the standard treatment for patients with locally advanced cervical cancer. However, many patients still relapse and die of metastatic disease. In this setting, the OUTBACK trial was conducted to investigate the effect of adjuvant chemotherapy after chemoradiation on survival in these patients. The results, recently published in The Lancet Oncology, showed that adjuvant chemotherapy after standard cisplatin-based chemoradiotherapy increases short-term toxicity without improving survival. Based on these results, adjuvant chemotherapy should not be administered in this setting.

Cervical cancer is the fourth most frequently diagnosed cancer and the fourth leading cause of cancer death in women, with an estimated 604,000 new cases and 342,000 deaths worldwide in 2020.¹ The current standard treatment for locally advanced cervical cancer is chemoradiation, yet a substantial number of women still experience relapse and die from distant metastatic disease. To address this issue, the OUTBACK trial was conducted to investigate the effect of adjuvant chemotherapy after chemoradiation on survival in these patients.2

Methods

The multicentre, open-label, OUTBACK phase 3 trial was conducted across 157 hospitals in Australia, China, Canada, New Zealand, Saudi Arabia, Singapore, and the USA. Eligible participants were adults (aged ≥18 year) with histologically confirmed squamous cell carcinoma, adenosquamous cell carcinoma, or adenocarcinoma of the cervix. In total, 919 participants were randomly assigned (1:1) to receive standard cisplatin-based chemoradiotherapy alone (n= 456) or followed by adjuvant chemotherapy with four cycles of carboplatin (n=463) . The primary endpoint was overall survival at 5 years.²

Study findings

After a median follow-up of 60 months, no significant differences were observed in the 5-year OS rates between the adjuvant chemotherapy and chemoradiotherapy-only groups (72% vs. 71%, respectively; HR[95%CI]: 0.90[0.70-0.17];p =0.81]. In total, there were 105 deaths in the adjuvant chemotherapy group, and 116 in the chemoradiotherapy-only group. The most common clinically significant grade 3-4 adverse events were decreased neutrophils (20% vs. 8% in the adjuvant chemotherapy and chemoradiotherapy-only groups, respectively) and anaemia (18% vs. 8%). Serious adverse events occurred in 30% vs. 22% of patients, most commonly due to infectious complications. There were no treatment-related deaths.²

These findings indicate that adjuvant chemotherapy, administered after standard cisplatin-based chemoradiotherapy, results in increased short-term toxicity without improving OS in locally advanced cervical cancer. Based on these results, the authors conclude that adjuvant chemotherapy should not be administered in this particular setting.²

References

1. Sung H, Ferlay J, Siegel RL, et al. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021;71(3):209-49.
2. 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. 2023;24(5):468-82.