PD-L1 CPS Does Not Enrich the Efficacy of Atezolizumab/Bevacizumab and Chemo in Advanced Cervical Cancer

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The addition of atezolizumab (Tecentriq) to bevacizumab (Avastin) and paclitaxel plus cisplatin or carboplatin performed similarly as frontline therapy in patients with persistent or recurrent metastatic cervical cancer with a PD-L1 combined positive score (CPS) of less than 1 or 1 or greater, according to findings from a prespecified exploratory post hoc analysis of the phase 3 BEATcc trial (NCT03556839) that were presented at the 2025 ESMO Gynecologic Cancers Congress.1

At a median follow-up of 32.8 months, the median progression-free survival (PFS) was 16.6 months with atezolizumab vs 10.5 months without in patients with a CPS of 1 or greater (HR, 0.54; 95% CI, 0.39-0.74). In the CPS less than 1 population, the median PFS was 13.6 months vs 10.2 months in the investigational and control arms, respectively (HR, 0.48; 95% CI, 0.28-0.82).

Interim overall survival (OS) results revealed median values of 33.2 months with atezolizumab vs 26.5 months without in patients with a CPS of 1 or greater (HR, 0.73; 95% CI, 0.51-1.06). In patients with a CPS of less than 1, the median OS was 37.3 months with atezolizumab vs 19.2 months without (HR, 0.43; 95% CI, 0.24-0.77).

“BEATcc confirms the clinical benefit of combined inhibition of immunosuppression and angiogenesis in recurrent or metastatic cervical cancer [and shows that] PD-L1 does not seem to be a robust biomarker guiding patient selection for immunotherapy in [this population],” Professor Kristina Lindemann, MD, PhD, presenting study author of NSGO-CTU, Oslo University Hospital and University of Oslo in Norway, said in a presentation of the data.

Platinum-based chemotherapy with or without bevacizumab is recommended as a standard of care for medically fit, chemotherapy-naive patients with advanced cervical cancer. Data from the phase 3 KEYNOTE-826 trial (NCT03635567) supported the addition of a checkpoint inhibitor to platinum-based chemotherapy with or without bevacizumab in this population of patients with a PD-L1 CPS of 1 or greater, with a 40% reduction in the risk of death with the addition of pembrolizumab (Keytruda; HR, 0.60; 95% CI, 0.49-0.74).2

However, that left an unmet need for patients with a CPS of less than 1 or those with unknown PD-L1 status.

The open-label, multi-center, randomized phase 3 BEATcc trial enrolled patients with recurrent or metastatic cervical cancer not amenable to curative therapy with a GOG/ECOG performance status of 0 or 1. Prior systemic anticancer therapy for recurrent or metastatic disease was not allowed, nor was bladder or rectal mucosa involvement in patients with pelvic disease. Available archival or fresh tumor sample was required for PD-L1 testing, although the study enrolled all-comers. PD-L1 status was evaluated centrally using the 22C3 immunohistochemistry assay scored by CPS using cutoffs of 1 and 10.

A total of 410 patients were randomly assigned 1:1 to receive intravenous therapy with 1200 mg of atezolizumab plus 15 mg/kg of bevacizumab and chemotherapy every 3 weeks or the same dose and schedule of bevacizumab and chemotherapy alone. Treatment was continued until disease progression or unacceptable toxicity.

Patients who achieved complete response after at least 6 cycles of therapy could discontinue chemotherapy and continue biological therapy alone.

Notably, crossover from the control arm at the time of progression was not allowed.

The primary end points were investigator-assessed PFS per RECIST 1.1 criteria and OS. Secondary end points included objective response rate, duration of response, time to first subsequent therapy, PFS2, and safety.

Previously, with a median follow-up of 32.9 months (95% CI, 31.2-34.6), investigators reported that the study met its dual primary end points in all-comers.3 The median PFS was 13.7 months with atezolizumab vs 10.4 months without (HR, 0.62; 95% CI, 0.49-0.78). Interim OS data revealed median values of 32.1 and 22.8 months with and without atezolizumab, respectively (HR, 0.68; 95% CI, 0.52-0.88).

To conduct the present analysis, HRs were calculated using stratified Cox regression analysis, and the predictive value of PD-L1 status was evaluated with interaction tests.1

A total of 313 patients of the 410 who had been randomly assigned to therapy had samples available for PD-L1 analysis. Regarding PD-L1 status in the investigational arm, 20% of patients had a CPS of less than 1, and 58% had a CPS of 1 or greater (CPS 1-10, 33%; CPS ≥10, 26%). In the control arm, 25% of patients had a CPS of less than 1 and 49% had a CPS of 1 or greater (CPS 1-10, 25%; CPS ≥10, 24%).

In the CPS population (n = 313), in the atezolizumab arm, the median age was 50 years (range, 24-90). Most patients had an ECOG/GOG performance score of 0 (65%), squamous cell carcinoma (79%), and recurrent disease at screening (75%). The predominant disease location at screening was pelvic and distant (52%). Primary therapy consisted of concurrent chemoradiotherapy (30%), surgery followed by chemoradiotherapy (35%), surgery and/or radiotherapy (10%), or nothing (25%).

Additional data indicated that the median time to second progression or death (PFS2) was 23.2 months with atezolizumab vs 15.9 months without in patients with a CPS of 1 or greater (HR, 0.62; 95% CI, 0.44-0.88). In patients with a CPS of less than 1, the median PFS2 was 24.3 months with atezolizumab vs 15.4 months without (HR, 0.49; 95% CI, 0.29-0.82).

“Atezolizumab plus bevacizumab and chemotherapy represents an effective first-line treatment option for patients with recurrent or metastatic cervical cancer and should be offered irrespective of CPS,” Lindemann stated. She added that the regimen is among the preferred first-line regimens for patients with recurrent or metastatic cervical cancer in the latest rendition of the National Comprehensive Cancer Network guidelines.4

Final OS results are expected in 2026.1

Disclosures: Lindemann reported personal fees for advisory board participation for AstraZeneca, Eisai, Genmab, GSK, Karyopharm, and MSD; speaker honoraria from AstraZeneca, GSK, and MSD; and research funding from GSK.

References

1. Giorgi UD, Mansi L, Martinez-Garcia J, et al. Efficacy according to PD-L1 status in the BEATcc (ENGOT-Cx10/GEICO 68-C/JGOG1084/GOG-3030) randomised phase 3 trial of first-line atezolizumab, chemotherapy and bevacizumab for metastatic, persistent or recurrent cervical cancer. Presented at: 2025 ESMO Gynecological Cancers Congress; June 19-21, 2024; Vienna, Austria. Abstract 10O.
2. Monk BJ, Colombo N, Tewari KS, et al. First-line pembrolizumab plus chemotherapy versus placebo + chemotherapy for persistent, recurrent, or metastatic cervical cancer: final overall survival results of KEYNOTE-826. J Clin Oncol. 2023;41(suppl 36):5505-5511. doi:10.1200/JCO.23.00914
3. Oaknin A, Gladieff L, Martínez-García J, et al. Atezolizumab plus bevacizumab and chemotherapy for metastatic, persistent, or recurrent cervical cancer (BEATcc): a randomised, open-label, phase 3 trial. Lancet. 2024;403(10421):31-43. doi:10.1016/S0140-6736(23)02405-4
4. NCCN. Clinical Practice Guidelines in Oncology. Cervical cancer, version 4.2025. Accessed June 19, 2025. https://www.nccn.org/professionals/physician_gls/pdf/cervical.pdf