The addition of the PD-L1 inhibitor tislelizumab (BGB-A317) to standard bevacizumab (Avastin) and platinum-doublet chemotherapy in the first-line setting prolonged progression-free survival (PFS), produced encouraging responses, and was well tolerated in patients with cervical cancer, according to preliminary results from a phase 2 trial (NCT05247619) presented at the 2023 ASCO Annual Meeting.
Efficacy-evaluable patients who received the combination (n = 37) achieved an overall response rate (ORR) of 78.4% (95% CI, 61.8%-90.2%); this consisted of 1 complete response and 28 partial responses. Eight patients achieved stable disease and no patients experienced disease progression.
The median time to response (TTR) was 1.5 months (range, 1.5-4.0). At a median follow-up of 5.1 months, both the duration of response (DOR) and PFS were not estimable. The disease control rate (DCR) was 100% (95% CI, 90.5%-100%).
Additional subgroup analyses of patient responses according to histological type and PD-L1 expression were performed for evaluable patients in the expansion cohort. Patients who were PD-L1 negative (n = 5) experienced an ORR of 100% (95% CI, 47.8%-100%); those who had low (n = 7) and high (n = 15) PD-L1 expression experienced ORRs of 71.4% (95% CI, 29.0%-96.3%) and 86.7% (95% CI, 59.5%-98.3%), respectively. ORRs achieved by patients with squamous cell carcinoma (n = 34) and adenocarcinoma (n = 3) were 79.4% (95% CI, 62.1%-91.3%) and 66.7% (95% CI, 9.4%-99.2%), respectively.
“Overall, the data from the study demonstrate that tislelizumab plus bevacizumab and chemotherapy showed promising efficacy and was well tolerated in the first line [for] patients with persistent, recurrent, or metastatic cervical cancer,” lead study author Jianqing Zhu, MD, of Zhejiang Cancer Hospital, in Hangzhou, China, said in a presentation of the data.
The multicenter study consisted of a safety run-in (part 1) and a cohort expansion portion (part 2). Patients with persistent, recurrent, or metastatic cervical cancer with no prior exposure to systemic therapy were enrolled on the trial. Other key inclusion criteria included an ECOG performance status of 0 or 1 and measurable disease according to RECIST v1.1 criteria.
Patients in part 1 and 2 were given either 200 mg of tislelizumab plus 7.5 mg/kg of bevacizumab and 50 mg/m2 of cisplatin or carboplatin at area under the curve of 5 and 175 mg/m2 of paclitaxel. Treatment was administered intravenously on day 1 of each 3-week cycle. Patients continued treatment until progressive disease, unacceptably toxicity, death, withdrawal of consent, or study termination by sponsor.
According to safety ranking considerations, patients were allowed to continue onto the dose-expansion portion of the trial if no more than 1 patient out of the first 6 to be enrolled in part 1 experienced a dose-limiting toxicity (DLT).
The primary end point was investigator-assessed PFS. A one-sample log-rank test with a sample size of 49 patients was utilized to compare PFS differences between the experimental regimen and a historical control. Key secondary end points included ORR, DCR, DOR, safety, and tolerability.
As no DLTs were observed in part 1, the study continued to part 2. A total of 50 patients were enrolled onto the expansion cohort from May 2022 to March 2023. The median age in this population was 50 years (range, 27-73). Regarding ECOG performance status, 76% had a status of 0 and 24% had a status of 1. At the time of initial diagnosis, 36% of patients had stage III disease, 28% had stage I disease, 18% had stage IV disease, and 18% had stage II disease. Over half (56%) of patients received prior surgery with or without chemoradiation, 30% of patients received prior chemoradiotherapy, 2% received chemotherapy alone, and 12% did not receive prior treatment.
Histological subtypes displayed by patients included squamous cell carcinoma (90%), adenocarcinoma (8%), or other histologic variants (2%). Most patients’ tumors had high PD-L1 expression (54.5%), defined as a combined positive score (CPS) of 20% or higher. Moreover, 27.3% of patients had low PD-L1 expression defined as a CPS between 5% and 20%, and 18.2% were PD-L1 negative, defined as a CPS of less than 5%. At the time of the data cutoff date, which was April 7, 2023, a total of 33 patients had detectable PD-L1 expression.
The median duration of treatment was 3.7 months. A total of 92% of patients experienced any-grade treatment-emergent adverse effects (TEAEs), including 44% who experienced a grade 3 or higher event. Ninety percent of patients experienced a treatment-related AE (TRAE); in 40% of patients, this was grade 3 or higher. Moreover, 36% of patients experienced a TRAE necessitating treatment modification. Serious AEs occurred in 22% of the population. Immune-related AEs were observed in 26% of patients and were only grade 1/2 in severity.
Common any-grade TRAEs occurring in 20% or more of patients included anemia (62%), alopecia (32%), white blood cell count decrease (28%), platelet count decrease (28%), and hypaesthesia (22%).