This trial (innovaTV-301) led to the full FDA approval for tisotumab in patients with metastatic cervical cancer. This is the first ADC targeting Tissue Factor that I am aware of. The data showed modest survival benefits, but this was more tolerable than traditional second- and third-line chemotherapy.
Recurrent cervical cancer is a life-threatening disease, with limited treatment options available when disease progression occurs after first-line combination therapy.
We conducted a phase 3, multinational, open-label trial of tisotumab vedotin as second- or third-line therapy in patients with recurrent or metastatic cervical cancer. Patients were randomly assigned, in a 1:1 ratio, to receive tisotumab vedotin monotherapy (2.0 mg per kilogram of body weight every 3 weeks) or the investigator’s choice of chemotherapy (topotecan, vinorelbine, gemcitabine, irinotecan, or pemetrexed). The primary end point was overall survival.
A total of 502 patients underwent randomization (253 were assigned to the tisotumab vedotin group and 249 to the chemotherapy group); the groups were similar with respect to demographic and disease characteristics. The median overall survival was significantly longer in the tisotumab vedotin group than in the chemotherapy group (11.5 months [95% confidence interval {CI}, 9.8 to 14.9] vs. 9.5 months [95% CI, 7.9 to 10.7]), results that represented a 30% lower risk of death with tisotumab vedotin than with chemotherapy (hazard ratio, 0.70; 95% CI, 0.54 to 0.89; two-sided P=0.004). The median progression-free survival was 4.2 months (95% CI, 4.0 to 4.4) with tisotumab vedotin and 2.9 months (95% CI, 2.6 to 3.1) with chemotherapy (hazard ratio, 0.67; 95% CI, 0.54 to 0.82; two-sided P<0.001). The confirmed objective response rate was 17.8% in the tisotumab vedotin group and 5.2% in the chemotherapy group (odds ratio, 4.0; 95% CI, 2.1 to 7.6; two-sided P<0.001). A total of 98.4% of patients in the tisotumab vedotin group and 99.2% in the chemotherapy group had at least one adverse event that occurred during the treatment period (defined as the period from day 1 of dose 1 until 30 days after the last dose); grade 3 or greater events occurred in 52.0% and 62.3%, respectively. A total of 14.8% of patients stopped tisotumab vedotin treatment because of toxic effects.
In patients with recurrent cervical cancer, second- or third-line treatment with tisotumab vedotin resulted in significantly greater efficacy than chemotherapy. (Funded by Genmab and Seagen [acquired by Pfizer]; innovaTV 301 ClinicalTrials.gov number, NCT04697628.)
A nod to our gynecologic oncologists. Minimally invasive surgery was significantly inferior to open radical hysterectomy for early-stage cervical cancer.
This is a Chinese study of neoadjuvant camrelizumab (PD1-MAb) + platinum-based chemo showing impressive effectiveness with an overall response rate (ORR) of 83% and a complete response (CR) of 19%. This drug is being studied in esophageal-SCC with promising reports as well. We will see if this gets studied in a Western population.
In the EORTC-55994 study, neoadjuvant chemotherapy followed by chemoradiation + surgery was not superior to chemoradiation for patients with stage IB2 – IIB cervical cancer. However, the toxicity was acceptable, so for patients with more locally advanced disease, it could be considered. Regardless, the SOC will remain concurrent chemotherapy and radiation for these patients.
FCS Hematology Oncology Review creates a platform for our physician network to observe the most recent articles and studies available in the oncology and hematology world. By sharing these articles we are building our wealth of knowledge of new observations and treatments as they come available.
