Key Takeaways from the OUTBACK Trial of Adjuvant Chemotherapy in Cervical Cancer

Bradley Monk, MD, FACCOG, FACS, a gynecologic oncologist at Arizona Oncology and the medical director of gynecologic oncology research at the US Oncology Network, discusses main takeaways from the OUTBACK trial (NCT01414608).

Within the phase 3 trial, investigators examined the use of adjuvant chemotherapy following chemoradiation as primary treatment for patients with locally advanced cervical cancer when compared to chemoradiation alone. A total of 900 patients were enrolled, including a group of patients who were at high risk for recurrence. The study examine the improvement of the overall survival (OS), progression-free survival (PFS), acute and long-term toxicities, patterns of disease recurrence, and quality of life in this patient population.

Despite the additional cycles of chemotherapy, investigators found the 5-year OS to be similar between the group that received chemotherapy alone (71%) and the group that received chemotherapy plus adjuvant chemotherapy (72%). Further, the PFS in the control group was 61% vs 63% in the experimental group, and similar disease recurrence patterns were reported between the 2 groups. These findings lead him to further understand and come up with the main takeaways from the trial.

Transcription:

0:08 | [There ar]e 4 lessons learned from the OUTBACK trial. And we should utilize these lessons to improve the quality of our ongoing and future clinical trials and locally advanced cervical cancer. Number 1, when post-progression survival is long, and crossover is common, or switching as we call it, the end point should never be OS. It should be PFS. Now as it turns out, it probably wouldn't have been positive anyways.

0: 44 | The second lesson is you have to use right agents at the time. The right agents at the time were carboplatin/paclitaxel, but as I mentioned in 2014, bevacizumab and carboplatin/paclitaxel became the global standard. And today, we have 2 randomized phase 3 trials of checkpoint inhibitors.

1: 09 | Third, we need to enroll the right patients. These patients that were enrolled, were actually not at high risk for recurrence, most of them were cured. We need to identify patients at the highest unmet medical need, enroll those patients with the right end point, and treat the with the right agents.

1:29 | Four, patients who receive radiation and chemotherapy are pretty beat up at the end of their treatment. Twenty percent of the patients, in fact, didn't even complete their chemotherapy and radiation. If you don't complete it, you're certainly not going to transition to a maintenance phase. Even when they finished it, another 20% or so didn't transition to a maintenance phase. If we want to change the impact of chemotherapy and radiation, this idea of a switch maintenance strategy after chemotherapy and radiation, is probably not wise. It may be better to start the systemic therapy during the radiation which after all, is when the systemic therapy cisplatin is started.