Sequential chemoradiation versus radiation alone or concurrent chemoradiation in adjuvant treatment after radical hysterectomy for stage IB1-IIA2 cervical cancer (STARS Study): A randomized, controlled, open-label, phase III trial.

Abstract

6007 Background: There are limited data from previous studies regarding whether the addition of chemotherapy to adjuvant radiation after radical surgery improves outcomes among patients with early-stage cervical cancer and adverse pathological factors. Methods: This was a prospective randomized trial including patients with FIGO 2009 stage IB1-IIA2 cervical cancer and squamous-cell, adenocarcinoma, or adenosquamous carcinoma with at least one adverse factor after radical hysterectomy. Patients were randomized 1:1:1 to receive adjuvant radiation alone, concurrent chemoradiation with weekly cisplatin (30-40 mg/m2), or sequential chemoradiation with cisplatin (60-75 mg/m2) plus paclitaxel (135-175 mg/m2) in 21 day cycles, given 2 cycles before and 2 cycles after radiotherapy respectively. The primary outcome was the rate of disease-free survival at 3 years. Results: A total of 1,048 patients were included in the study (350, radiation alone; 345, concurrent chemoradiation; and 353, sequential chemoradiation). Overall, the median follow-up was 56 months and the median age of patients was 48 years. Most patients (75%) had stage IB1 or IIA1 disease. The three groups were similar with respect to histologic subtypes, the rate of lymphovascular invasion, parametrial, surgical margin and deep stromal involvement, tumor grade, rate of use of minimally invasive surgery, and neoadjuvant chemotherapy, except for lymph-node involvement that was lowest in radiation alone arm. In the intention-to-treat population, sequential chemoradiation was associated with a higher rate of disease-free survival than radiation alone (3-year rate, 90·0% vs. 82·0%; HR 0·52; 95% CI, 0·35 to 0·76) and concurrent chemoradiation (90·0% vs. 85·0%; HR 0·65; 95% CI, 0·44 to 0·96), differences remained after adjustment for lymph-node involvement. Sequential chemoradiation was also associated with a higher rate of overall survival than radiation alone (5-year rate, 92·0% vs. 88·0%; HR for death from cancer, 0·58; 95% CI, 0·35 to 0·95). However, neither disease-free survival nor cancer death risk was different between patients treated with concurrent chemoradiation or radiation alone. Conclusions: In this trial, sequential chemoradiation, rather than concurrent chemoradiation, resulted in a higher disease-free survival and lower risk of cancer death than radiation alone among women with early-stage cervical cancer after radical surgery. Clinical trial information: NCT00806117.

Adjuvant treatment in early stage cervical cancer—does more equal better?

“…Treatment discontinuation rates were high in the chemotherapy arms, 5 with 62% completion in the concurrent arm and 73% in the sequential arm. These results are relatively similar to those reported in other cervical cancer trials, and highlight the importance of improving toxicity management in clinical practice and future studies.…”

“…The trial recruited across eight centers in China between 2008 and 2015 and included patients with FIGO stage IB1-IIA2 squamous cell, adenosquamous carcinoma, and adenocarcinoma of the cervix, and at least one risk factor following radical hysterectomy including lymph node metastasis, positive parametrium or margin, lymphovascular space involvement, or deep stromal invasion. 5 One thousand and fortyeight women were randomized to adjuvant radiation (radiation arm), concurrent chemo-radiation with weekly cisplatin (concurrent arm), or sequential treatment with 3 weekly cisplatin and paclitaxel, administered two cycles before and two after radiotherapy (sequential arm). The majority of enrolled patients had squamous cell histology (>85%) and tumor size was ≤4 cm in approximately 75% of women.…”

Major clinical research advances in gynecologic cancer in 2020

“…A phase III trial comparing sequential chemoradiation vs. radiation alone or concurrent chemoradiation in adjuvant treatment after radical hysterectomy for stage IB1–IIA2 cervical cancer (STARS study, NCT00806117) has been reported in ASCO annual meeting [ 8 9 ]. In the intention-to-treat population, sequential chemoradiation was associated with a higher 3-year disease-free survival than radiation alone (90% vs. 82%; hazard ratio [HR]=0.52; 95% confidence interval [CI]=0.35–0.76) and concurrent chemoradiation (90% vs. 85%; HR=0.65; 95% CI=0.44–0.96).…”

Updates on systemic therapy for cervical cancer

“…A recently concluded phase III randomized controlled trial (RCT) showed sequential chemoradiation (paclitaxel-cisplatin followed by radiotherapy, again followed by paclitaxel-cisplatin) after surgery resulted in improved disease-free survival (DFS) and lowered the risk of death from cervical cancer in patients with adverse pathological factors 19 . In this study, 1048 patients were equally randomized across three arms to receive either adjuvant RT, CCRT or sequential chemotherapy followed by RT after radical surgery 19 . Data showed that DFS and OS were significantly improved in the sequential arm as compared to RT alone [three-year DFS rate, 90 vs .…”

“…82%; hazard ratio (HR) 0.52; 95% confidence interval (CI), 0.35-0.76 and five-year risk of death, 92 vs . 88%; HR, 0.58; 95% CI, 0.35-0.95] 19 . There was improved DFS for sequential arm as compared to concurrent arm (90 vs. 85%; HR 0.65; 95% CI, 0.44-0.96) 19 ; however, there was no difference between the CCRT versus RT alone arms 19 and requires confirmation in future trials.…”