The administration of adjuvant carboplatin and paclitaxel following standard cisplatin-based chemoradiation failed to demonstrate an improvement in progression-free survival or overall survival in women with locally advanced cervical cancer, according to findings from the phase 3 OUTBACK trial.
The administration of adjuvant carboplatin and paclitaxel following standard cisplatin-based chemoradiation failed to demonstrate an improvement in progression-free survival (PFS) or overall survival (OS) in women with locally advanced cervical cancer, according to findings from the phase 3 OUTBACK trial that were presented at the 2021 ASCO Annual Meeting.
“Adjuvant chemotherapy given after standard platinum-based chemoradiation for women with locally advanced cervical cancer did not improve OS or PFS. So, the standard treatment should continue to be pelvic chemoradiation with concurrent weekly cisplatin,” lead study author Linda R. Mileshkin, MD, medical oncologist, Peter McCallum Cancer Centre, Melbourne, Australia, said during a presscast ahead of the meeting.
“Our findings don't support giving adjuvant chemotherapy with carboplatin and paclitaxel after chemoradiation with weekly cisplatin. Further research should focus on adjuvant therapies that might be more tolerable and effective when given after standard therapy,” she added.
In the international, randomized phase 3 OUTBACK trial (NCT01414608), the investigators aimed to determine the survival effects from administering adjuvant chemotherapy after standard chemoradiation, compared with standard chemoradiation alone, in 919 patients with locally advanced cervical cancer recruited from April 2011 to June 2017
In total, investigators randomized patients 1:1 to receive either standard cisplatin-based chemo-radiation followed by adjuvant chemotherapy (n = 463) with 4 cycles of carboplatin and paclitaxel or standard cisplatin-based chemo-radiation (n = 456). Adjuvant chemotherapy was administered in 361 women (78%).
Trial eligibility consisted of locally advanced cervical cancer (FIGO 2008 stage IB1 & node positive, IB2, II, IIIB, or IVA); an ECOG score of 0 to 2; squamous cell, adenocarcinoma, or adenosquamous cancer; no nodal disease above L3/4; and disease that was suitable for primary treatment with chemo-radiation with curative intent. Women were stratified by nodal status, participating site, FIGO stage, age, and planned extended-field radiotherapy.
OS at 5 years served as the primary end point. Secondary endpoints included PFS, adverse events (AEs), and patterns of disease recurrence.
Median follow-up was 60 months (IQR, 45-65).
The adjuvant chemotherapy arm demonstrated similar OS at 5 years, compared with the control arm (72% vs 71%, respectively; P = .8), for an HR of 0.90, (95% CI, 0.70-1.17), as well as similar PFS at 5 years (63% vs 61%; P = .61), for an HR of 0.87 (95% CI, 0.70-1.08).
In addition, patterns of disease recurrence were similar in the two treatment groups.
“Even when we looked at subsets of women with high-risk disease, such as those with node positive involvement, there was no benefit from the intervention,” Mileshkin added.
Within a year of randomization, grade 3 to 5 AEs typically seen with chemotherapy occurred in significantly more patients in the adjuvant chemotherapy arm, compared with the control arm (81% vs 62%, respectively). Lastly, Mileshkin noted that quality of life was worse during adjuvant chemotherapy and for the following 3 to 6 months, but returned to being similar between the groups from 12 months onwards.
Cervical cancer is a major global health problem, according to Mileshkin, with more than half a million women diagnosed with the disease each year, “and more than 3000 women will die of this cancer each year, making it the fourth leading cause of cancer-related death in women. … But most women die from cervical cancer…because of the development of distant metastatic disease.”
Although prior, smaller studies suggested that giving more chemotherapy after chemoradiation could improve survival. “And these findings changed practice in some centers,” Mileshkin explained. “However, the international community felt that there were some flaws in these trials and that it was important to perform a confirmatory trial.”
ASCO president Lori J. Pierce, MD, FASTRO, FASCO, added to the OUTBACK trial’s significance. “As we heard, physicians are currently using adjuvant chemotherapy based upon preliminary data and promise it could work. We clearly see it does not work and need to discontinue that practice,” she said. “This tells us that, as clinical researchers, 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.”
Mileshkin LR, MooreKN, Barnes E, et al. Adjuvant chemotherapy following chemoradiation as primary treatment for locally advanced cervical cancer compared to chemoradiation alone: The randomized phase 3 OUTBACK Trial (ANZGOG 0902, RTOG 1174, NRG 0274). Presented at: American Society of Clinical Oncology Annual Meeting; June 4-8, 2021; Virtual. Abstract LBA3.