Treatment with chemotherapy following the standard chemoradiation treatment failed to improve multiple survival outcomes in women with locally advanced cervical cancer.
The addition of chemotherapy after the standard cisplatin-based chemoradiation failed to improve overall- and progression-free survival in women with locally advanced cervical cancer, according to data from the phase 3 OUTBACK trial.
“Adjuvant chemotherapy given after standard platinum-based chemoradiation for women with locally advanced cervical cancer did not improve overall survival [OS] or progression-free survival [PFS]. So, the standard treatment should continue to be pelvic chemoradiation with concurrent weekly cisplatin,” lead study author Dr. Linda R. Mileshkin, a medical oncologist at Peter McCallum Cancer Centre in Melbourne, Australia, said during a news briefing ahead of the 2021 American Society of Clinical Oncology (ASCO) Annual 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, 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.
In total, investigators randomized patients 1:1 to receive either standard cisplatin-based chemoradiation followed by adjuvant chemotherapy (463 patients) with four cycles of carboplatin and paclitaxel or standard cisplatin-based chemoradiation (456 patients). Adjuvant chemotherapy was administered in 361 women (78%).
Measuring OS (time that a patient with cancer is still alive) at five years served as the main goal of the study. Other goals included assessing PFS (time during and after treatment when the patient lives without disease progression), side effects, and patterns of disease recurrence.
The adjuvant chemotherapy treatment group demonstrated similar OS at five years, compared with the chemoradiation group (72% vs. 71%, respectively), as well as similar PFS at five years (63% vs 61%).
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, serious or severe side effects typically seen with chemotherapy occurred in significantly more patients in the adjuvant chemotherapy group, compared with the chemoradiation alone group (81% vs 62%, respectively). Lastly, Mileshkin noted that quality of life was worse during adjuvant chemotherapy and for the following three to six 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 3,000 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.”
Previous smaller studies had 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 Dr. Lori J. Pierce 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.”
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