Toripalimab plus bevacizumab, SoC demonstrates promising efficacy for cervical cancer

Preliminary results of a single-arm, open-label, phase II trial demonstrated the efficacy of a combination regimen comprising toripalimab, bevacizumab, and platinum-based chemotherapy for women with refractory, recurrent, or metastatic cervical cancer.

“[This combination showed] a promising response rate and disease control rate (DCR), and it appears tolerable,” said Dr Alexander Melamed from Massachusetts General Hospital, Boston, Massachusetts, US, who presented the findings at SGO 2023 on behalf of study investigator Dr Peng Peng from the Peking Union Medical College Hospital, Beijing, China.

The investigator-assessed objective response rate (ORR) was 77.3 percent, corresponding to partial response in 17 participants. DCR was 95.5 percent, translating to 21 out of 22 participants in the intention-to-treat cohort. Four patients had stable disease. Only one patient had progressive disease.

Among responders, median duration of response has not been reached. Median time to response was 1.5 months. [SGO 2023, Late Breaking Abstracts session]

Twenty-one participants reported at least one any-grade treatment-related adverse event (TRAE). Five had serious AEs. Only two patients discontinued as a result of treatment-related toxicity. No grade ≥3 immune-related AEs were reported. “[There was] one death from acute heart failure, which may have been related to the treatment,” noted Melamed.

The most common TRAEs were related to bone marrow suppression from the chemo regimen, he continued. Ten patients had grade ≥3 neutropenia, while four had grade ≥3 leukopenia. There were two cases of grade ≥3 rectovaginal fistulas which, according to Melamed, is not unexpected in this population. One patient developed sudden deafness.

“[The] immune-related AEs were all low-grade and mostly endocrinologic,” he said. Eight patients had increased adrenocorticotropic hormone, seven had decreased serum cortisol, and seven had thyroid dysfunction (all all-grade).

First PD-1 inhibitor approved in China

“Patients with recurrent/metastatic cervical cancer represents a poor prognostic group, with a 5-year survival of 17 percent. Currently, treatment options are limited for recurrent/metastatic cervical cancer, and there are high unmet clinical needs,” noted Peng in the presentation.

Immune checkpoint inhibitors, in combination with SoC, have been approved for patients with PD-L1-positive advanced cervical cancer, noted Melamed.

“Toripalimab is the first PD-1 inhibitor that has been approved for several indications in China,” he said. “Previous studies have suggested that the addition of this drug to chemoradiotherapy in cervical cancer shows promising efficacy and manageable toxicity in refractory, recurrent, and metastatic cervical cancer.”

As such, the team aimed to evaluate the efficacy and safety of toripalimab in combination with bevacizumab and platinum-based chemo as first-line treatment in this patient setting. Participants were eligible if they had no prior systemic therapy for their recurrent disease, were not candidates for local curative therapy, and had ECOG PS 0/1 and measurable disease.

Twenty-four women (mean age 54.5 years) received toripalimab 240 mg plus bevacizumab 7.5 mg/kg and a paclitaxel doublet on day 1. They received six cycles of the regimen Q3W. Following which, they were continued on toripalimab and bevacizumab for 12 months until disease progression or intolerable toxicity.

Nineteen women had squamous cell carcinoma; the rest had adenocarcinoma. Most patients had early-stage disease. Nearly half had distant metastasis, and about a third had local recurrence plus distant metastasis. A third had received chemoradiotherapy.

Treatment is ongoing for 13 patients at the time of data cutoff. Of the 10 cases of treatment discontinuation, half were due to disease progression. Median treatment duration was 5.3 months.

Of note, Peng specified in the presentation that toripalimab has yet to be approved for use outside of clinical trials. Thus, the study evaluated the investigational use of the drug in this patient cohort.