For Women with Locally Advanced Cervical Cancer, Adjuvant Chemotherapy Not Recommended After Chemoradiation

Linda R. Mileshkin, MBBS, MD

A new study showed that the use of adjuvant chemotherapy with carboplatin and paclitaxel after chemotherapy plus radiation—also called “chemoradiation”—with cisplatin did not provide any benefit for women with locally advanced cervical cancer, according to data presented at the 2021 ASCO Annual Meeting.

Adjuvant therapy is used after primary treatment in the attempt to destroy any remaining cancer cells in the tumor. Locally advanced cervical cancer means that the tumor within the cervix has grown into the surrounding tissues, but has not spread to other organs.

According to Linda R. Mileshkin, MBBS, MD, Medical Oncologist at Peter MacCallum Cancer Centre in Victoria, Australia, continuing with adjuvant chemotherapy after standard-of-care chemoradiation did not improve the survival or the time without disease progression in women with locally advanced cervical cancer.

Based on these findings, Dr. Mileshkin reported that “pelvic chemoradiation with weekly cisplatin should remain the standard-of-care treatment for women with locally advanced cervical cancer,” and should not be followed by adjuvant chemotherapy with carboplatin and paclitaxel.

Cervical Cancer

When women are not screened early for cervical cancer, it can develop into locally advanced cancer, which does not have many treatment options.

Chemotherapy with cisplatin plus radiation to the pelvis has been the standard of care in the past 2 decades. But cervical cancer still comes back in a significant percentage of women after chemotherapy and radiation, and often progresses to metastatic (spreading to other organs) disease, leading to death.

The OUTBACK Trial

The OUTBACK trial was designed to address this issue. Of the 926 women with cervical cancer recruited for this international study, 919 women with cervical cancer suitable for chemoradiation were allowed to participate in the study. Patients were assigned to 1 of 2 study groups (about 450 patients in each group), and received either standard-of-care chemoradiation, or the same chemoradiation followed by 4 cycles of adjuvant chemotherapy with carboplatin plus paclitaxel.

The majority of the women were in their mid-40s, and only 15% of women in the study were older than 60. Most had a good performance status (meaning they were still able to carry out daily activities), and three-quarters (75%) of women were white.

According to Dr. Mileshkin, the patients’ adherence to treatment was good. “We consider that chemoradiation was fully completed in 77% of patients in each arm,” she noted. “Of those who received adjuvant chemotherapy, most were able to complete all 4 cycles, with 70% receiving all 4 cycles of carboplatin at full dose, with no delay, and findings were similar for paclitaxel.”

The results were similar among all patients in the study, meaning that adding adjuvant chemotherapy with carboplatin and paclitaxel did not show a benefit. The overall 5-year survival was similar in the 2 groups—71% in the standard chemoradiation group compared with 72% in the adjuvant chemotherapy group.

The time without disease progression was also similar in the 2 groups—61% in the standard-of-care chemoradiation group and 63% in the adjuvant chemotherapy group.

“However, there was some evidence of a reduced effect of adjuvant chemotherapy in women who were age 60 or older,” Dr. Mileshkin said. Most patients in the study did not have disease recurrence after treatment, but of the patients whose cancer did come back, there was no difference between the 2 groups, again showing no benefit of adjuvant therapy after chemoradiation.

Side Effects

As can be expected, more side effects were seen in the patients who received adjuvant chemotherapy. These side effects most often involved blood side effects such as anemia or low platelet counts, hair loss, fatigue, aching muscles, and neuropathy (numbness or tingling in the hands and feet), nausea, and vomiting.

After 1 year or more, the differences in side effects between the 2 groups became less obvious. However, neuropathy, which can be distressing for patients, remained significantly higher in the patients who received adjuvant chemotherapy.

Quality of life was worse in women who received adjuvant chemotherapy during treatment and for 3 to 6 months after, but from 12 to 36 months it was similar to those who received standard-of-care treatment.

“The study confirms that chemoradiotherapy alone is currently our best possible treatment for women with locally advanced cervical cancer. Not only is there no benefit with adjuvant chemotherapy, but severe side effects are also increased,” Dr. Mileshkin said in a press release.