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).

Author:

Mileshkin Linda R.1,Moore Kathleen N.2,Barnes Elizabeth3,Gebski Val4,Narayan Kailash5,Bradshaw Nathan4,Lee Yeh Chen3,Diamante Katrina4,Fyles Anthony W.6,Small William7,Gaffney David K.8,Khaw Pearly5,Brooks Susan9,Thompson J Spencer10,Huh Warner King11,Carlson Matthew12,Mathews Cara Amanda13,Rischin Danny14,Stockler Martin R.3,Monk Bradley J.15

Affiliation:

1. Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, Australia;

2. Stephenson Cancer Center, Oklahoma City, OK;

3. NHMRC Clinical Trials Centre, University of Sydney, Sydney, NSW, Australia;

4. NHMRC Clinical Trials Centre, University of Sydney, Sydney, Australia;

5. Department of Radiation Oncology, Peter MacCallum Cancer Centre, Melbourne, Australia;

6. NCIC-CTG, Radiation Medicine Program, Princess Margaret Cancer Centre, Toronto, ON, Canada;

7. Loyola University Medical Center, Maywood, IL;

8. Huntsman Cancer Institute at the University of Utah, Salt Lake City, UT;

9. Auckland Hospital, Auckland, New Zealand;

10. Univ of Oklahoma Health Sci Ctr, Oklahoma City, OK;

11. University of Alabama at Birmingham, Birmingham, AL;

12. The University of Texas Southwestern Medical Center, Dallas, TX;

13. Program in Women’s Oncology, Department of Obstetrics and Gynecology, Women and Infants Hospital, Brown University, Providence, RI;

14. Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia;

15. Arizona Oncology (US Oncology Network), University of Arizona College of Medicine, Phoenix, AZ;

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.

Funder

National Health & Medical Research Council of Australia

Publisher

American Society of Clinical Oncology (ASCO)

Subject

Cancer Research,Oncology

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