Adjuvant chemotherapy following chemoradiation as primary treatment for locally advanced cervical cancer compared to chemoradiation alone: The randomized phase III OUTBACK Trial (ANZGOG 0902, RTOG 1174, NRG 0274).

Abstract

LBA3 Background: Cervical cancer is a common cause of cancer-related death among women worldwide. Standard treatment for locally advanced disease is chemoradiation. However, a significant percentage of women still relapse and die from the development of distant metastatic disease. OUTBACK was designed to determine the effects of giving adjuvant chemotherapy after chemoradiation on survival. Methods: OUTBACK is an international randomized phase III trial of the Gynecologic Cancer InterGroup (GCIG). Participating groups (countries) included ANZGOG (Australia and New Zealand), NRG (USA, Saudi Arabia, Canada, China), and Singapore. Eligible women had locally advanced cervical cancer (FIGO 2008 stage IB1 and node positive, IB2, II, IIIB or IVA) that was suitable for primary treatment with chemo-radiation with curative intent. Women were randomly assigned to either standard cisplatin-based chemo-radiation (control) or standard cisplatin-based chemo-radiation followed by adjuvant chemotherapy (ACT) with 4 cycles of carboplatin and paclitaxel, after stratification for nodal status, participating site, FIGO stage, age, and planned extended-field radiotherapy. The primary end point was overall survival (OS) at 5 years. Secondary endpoints included progression-free survival (PFS); adverse events (AE); and patterns of disease recurrence. The target sample size of 900 provided 80% power with 95% confidence to detect an improvement in OS at 5 years from 72% (control) to 80% (ACT), with some over-accrual to account for non-compliance with ACT and loss to follow-up. Results: 919 of 926 women recruited from April 2011 to June 2017 were eligible and included in the primary analysis: 463 assigned ACT, 456 control. ACT was started in 361 (78%) women assigned to receive it. Median follow-up was 60 months (IQR 45-65). OS at 5 years was similar in those assigned ACT versus control (72% vs 71%, difference <1%, 95% CI -6 to +7; P = 0.91). The hazard ratio for OS was 0·91, (95% CI 0.70 to 1.18). PFS at 5 years was similar in those assigned ACT versus control (63% vs 61%, difference 2%, 95% CI -5 to +9; P = 0.61). The hazard ratio for PFS was 0·87, (95% CI 0.70 to 1.08). AE of grade 3-5 within a year of randomisation occurred in 81% who were assigned and received ACT versus 62% assigned control. There was no evidence of differences between treatment groups in AE beyond 1 year of randomisation. Patterns of disease recurrence were similar in the two treatment groups. Conclusions: Adjuvant chemotherapy given after standard cisplatin-based chemoradiation for women with locally advanced cervical cancer did not improve OS or PFS. Clinical trial information: ACTRN12610000732088.

Adjuvant trials suggest changes to non–small cell lung cancer treatment paradigm

“…Data from the OUTBACK trial (ACTRN12610000732088) illustrated similar progressionfree survival rates (63% vs 61%; 95% CI, -5 to +9; P = 0.61) without improved overall survival (72% vs 71%; 95% CI, -6 to +7; P = 0.91) at 5 years for patients with advanced cervical cancer who were given adjuvant chemotherapy after the administration of cisplatin-based chemoradiation. 1,4 IMpower010 (ClinicalTrials.gov identifi er NCT02486718), a randomized, global, open-label trial of atezolizumab (Tecentriq), an anti-PD-L1, versus best supportive care after adjuvant treatment, studied patients with resected stage IB to IIIA NSCLC. A total of 1280 patients were enrolled; they received 4 cycles of cisplatin with vinorelbine, docetaxel, pemetrexed, or gemcitabine.…”

Combined modality management of advanced cervical cancer including novel sensitizers

“…Patients randomized to four cycles of adjuvant carboplatin AUC 5 and paclitaxel 155 mg/m 2 , dosed 3-weekly, after completion of definitive cisplatin chemoradiation did not have significant improvement in progression-free survival or overall survival, compared with standard cisplatin chemoradiation alone (Table 1). 36 At present, adjuvant carboplatin plus paclitaxel after cisplatin chemoradiation cannot be considered standard therapy for patients with locally advanced cervical cancer.…”

Radiation oncology management of stage III and IVA cervical carcinoma

“…Results presented during the 2021 ASCO Annual Meeting did not separate the stage III or IVA subgroups. For all stages together in 919 participants, there was no benefit for outback chemotherapy 33. With a median follow-up of 60 months, 5 year overall survival was 71% versus 72% in the control versus intervention group, with a hazard ratio of 0·91 (95% CI 0.70 to 1.18).…”