Sequential CRT Wins in Post-Op Cervical Cancer

Sequential chemoradiotherapy (CRT) after radical hysterectomy for early-stage cervical cancer topped other adjuvant approaches in a phase III trial from China.

In the randomized, three-arm STARS study involving more than 1,000 women, sequential CRT was associated with improved disease-free survival (DFS) over radiation therapy alone, with 3-year rates of 90.0% versus 82.0%, respectively (HR 0.52, 95% CI 0.35-0.76), according to Ji-Hong Liu, MD, of Sun Yat-sen University Cancer Center in Guangzhou, China, and colleagues.

Sequential CRT was also associated with improved DFS compared with concurrent CRT, which had a 3-year rate of 85.0% (HR 0.65, 95% CI 0.44-0.96), the group reported in JAMA Oncology.

After adjusting for lymph node involvement, overall survival (OS) was superior with sequential CRT compared with radiation alone, yielding a 5-year rate of 92% versus 88% (HR 0.58, 95% CI 0.35-0.95, P=0.03).

Subgroup analyses showed that sequential CRT improved DFS outcomes in high-risk women compared with radiation alone (HR 0.48, 95% CI 0.26-0.88), as well as in the intermediate-risk group (HR 0.56, 95% CI 0.34-0.91).

Sequential CRT “should be considered a preferred adjuvant treatment after radical hysterectomy for patients with early-stage cervical cancer,” Liu and co-authors concluded.

Concurrent CRT, on the other hand, failed to significantly improve DFS or OS compared with radiation alone.

In an accompanying editorial, Bradley Monk, MD, of the University of Arizona College of Medicine in Phoenix, and colleagues called the findings “provocative” and “promising,” but also pointed to various limitations. For one, patients assigned to concurrent CRT did not tolerate it well, which is not consistent with U.S. experience and “underpowers this arm for reliable comparison,” the editorialists wrote.

In the radiation-only arm, 98.8% of patients completed their assigned treatment, as compared to 62.3% in the concurrent CRT arm and 73.4% in the sequential CRT arm.

“Next, lymph node metastasis, a key risk factor for disease recurrence, was biased to the [concurrent] and [sequential] arms, and 19.1% to 22.7% of patients required neoadjuvant chemotherapy to permit surgery, making this a higher-risk population than would normally receive surgery in the U.S.,” Monk and colleagues argued.

“Moreover, the eligibility combined two prognostically distinct patient groups, intermediate-risk and high-risk, into one patient cohort. Not only were the prognostic differences internally confirmed in this trial, but also the benefit of [sequential CRT] was best demonstrated in patients at high risk, not intermediate risk,” they continued. “We submit that this finding further supports the U.S. GOG risk-based strategy regarding the intensity of adjuvant therapy.”

Due to the lack of a risk-based approach in STARS, Monk’s group concluded that sequential CRT will not be fully embraced as a new standard approach for all cervical cancer patients eligible for adjuvant therapy after radical hysterectomy, and will need to await results of the GOG 263 and NRG 0724 trials.

STARS included 1,048 women (median age 48) with stage IB-IIA cervical cancer per International Federation of Gynecology and Obstetrics (FIGO) criteria. Patients were treated at eight hospitals in China and randomized 1:1:1 to radiation alone (total dose of 45-50 Gy), concurrent CRT with weekly cisplatin, or sequential CRT with cisplatin and paclitaxel for two cycles delivered prior and after radiation.

Liu’s group noted that baseline characteristics were well-balanced between the three treatment groups, except for the rate of lymph node metastases, at 18.3% in the radiation-alone group versus 30.1% with concurrent CRT and 29.7% with sequential therapy.

For safety, the radiation-alone group had the lowest rates of grade 3/4 adverse events (AEs), at 12.9%, as compared to 28.5% in the concurrent CRT arm and 25.3% with sequential CRT. Concurrent CRT was associated with higher rates of gastrointestinal AEs compared with the sequential approach, while the sequential CRT group had higher rates of lymphocele and peripheral sensory neuropathy.