Cervical cancer is the fourth most common cancer in women worldwide, and the leading cause of cancer-related death among women in Eastern, Western, Middle, and Southern Africa. Globally, in 2018, approximately 570,000 women were diagnosed with cervical cancer, and 311,000 women died. In the United States, the American Cancer Society estimates that in 2021, about 14,480 new cases of invasive cervical cancer will be diagnosed, and about 4,300 women will die of the disease.
Despite chemoradiation, the standard treatment for locally advanced cervical cancer, a significant percentage of women relapse and die of distant metastatic disease. The international randomized phase III OUTBACK trial was designed to determine the effects on survival of giving adjuvant chemotherapy after chemoradiation. The findings from the study showed that women with locally advanced cervical cancer receiving adjuvant chemotherapy after standard cisplatin-based chemoradiation did not experience improved overall or progression-free survival. In addition, the therapy was associated with increased side effects.
Linda R. Mileshkin, MD
These findings were presented by Linda R. Mileshkin, MD, and colleagues during the 2021 ASCO Annual Meeting (Abstract LBA3).
Study Methodology
The researchers enrolled 919 women with locally advanced cervical cancer into the study who were suitable for primary treatment with chemoradiation with curative intent. Women were randomly assigned to either standard cisplatin-based chemoradiation (control group) or standard cisplatin-based chemoradiation followed by adjuvant chemotherapy with four cycles of carboplatin and paclitaxel, after stratification for nodal status, participating site, International Federation of Gynecology and Obstetrics (FIGO) stage, age, and planned extended-field radiotherapy.
The primary endpoint was overall survival at 5 years; secondary endpoints included progression-free survival, adverse events, and patterns of disease recurrence.
Key Results
In the primary analysis, 463 women were assigned to receive adjuvant chemotherapy and 456 were in the control group. Cisplatin-based chemoradiation was started in 361 women (78%) assigned to receive the therapy. Median follow-up was 60 months (interquartile range [IQR] = 45–65 months).
Overall survival at 5 years was similar in those assigned adjuvant chemotherapy vs the control group (72% vs 71%, difference = < 1%, 95% confidence interval [CI] = –6 to +7; P = .91). The hazard ratio for overall survival was 0.91 (95% CI = 0.70–1.18). Progression-free survival at 5 years was similar in those receiving adjuvant chemotherapy vs the control group (63% vs 61%, difference = 2%, 95% CI = –5 to +9; P = .61). The hazard ratio for progression-free survival was 0.87 (95% CI = 0.70–1.08).
KEY POINTS
- At 5 years, overall survival was comparable for those receiving the additional adjuvant chemotherapy and those receiving standard care—72% vs 71%, respectively.
- Patterns of disease recurrence were similar in both treatment groups—63% of patients receiving additional chemotherapy vs 61% who received chemoradiation alone.
- Grade 3 to 5 adverse events were experienced by 81% of patients receiving additional chemotherapy vs 62% in the standard treatment group.
Grade 3 to 5 adverse events within a year of random assignment occurred in 81% of patients who were assigned and received adjuvant chemotherapy vs 62% of those assigned to the control group. There was no evidence of differences between treatment groups in adverse events beyond 1 year of random assignment. Patterns of disease recurrence were similar in the two treatment groups.
“Adjuvant chemotherapy given after standard cisplatin-based chemoradiation for women with locally advanced cervical cancer did not improve overall survival or progression-free survival,” concluded the study authors.
Clinical Significance
During an ASCO press briefing highlighting the clinical significance of this study, ASCO President Lori J. Pierce, MD, FASTRO, FASCO, commented: “This is an important trial in that the results clearly show that patients with locally advanced cervical cancer do not benefit from adjuvant chemotherapy. So, those physicians who are currently using adjuvant chemotherapy based on preliminary data in the promise it could work will clearly see that it does not work, and they need to discontinue that practice.”
She continued: “What the adjuvant chemotherapy did do was cause unnecessary side effects for the patients who received it. So, it tells us that in clinical research we need more trials for patients with locally advanced cervical cancer using a different therapeutic approach. And I think it also clearly shows the importance of the outcomes of clinical trials, even if the results are negative. Both positive trials and negative trials clearly inform practice.”
Disclosure: Funding for this study was provided by the National Health & Medical Research Council of Australia. For full disclosures of the study authors, visit coi.asco.org.
