1. Median overall survival was 11.5 months in the tisotumab vedotin group and 9.5 months in the chemotherapy group, with an HR of 0.70 (significant).
2. Adverse events grade ≥3 occurred in 52.0% of the tisotumab vedotin group and 62.3% in the chemotherapy group.
Evidence Rating Level: 1 (Excellent)
Study Rundown: Immunotherapy alone or in combination with standard care has improved outcomes in recurrent cervical cancer however these outcomes remain suboptimal. Tisotumab vedotin, an antibody-drug conjugate that targets tissue factor and carries a microtubule-disturbing payload, has shown some promising results in phase II trials. This phase III trial investigates the efficacy of tisotumab vedotin compared to chemotherapy as second or third-line therapy for recurrent cervical cancer. The primary endpoint was overall survival (OS), and secondary endpoints included progression-free survival (PFS), objective response rate (ORR), time to response, duration of response (DoR), safety, and quality of life (QoL). Median OS was 11.5 months in the tisotumab vedotin group and 9.5 months in the chemotherapy group, with HR 0.70 (significant). OS at 12 months was 48.7% and 35.3%, respectively. Median PFS was 4.2 months in the tisotumab vedotin group and 2.9 months in the chemotherapy group, with an HR of 0.67 (significant). PFS at 6 months was 30.4% and 18.9%, respectively. ORR was 17.8% in the tisotumab vedotin group and 5.2% in the chemotherapy group with an OR 4.0 (significant). Median DoR was 5.3 months in the tisotumab vedotin group and 5.7 months in the chemotherapy group. The median time to response was 1.6 months and 1.7 months, respectively. With regards to safety, grade ≥3 events occurred in 52.0% in the tisotumab vedotin group and 62.3% in the chemotherapy group, with the most common events being anemia (8.4% vs. 27.6%), urinary tract infection (4.4% vs. 7.1%), and neutropenia (3.6% vs. 13.4%, respectively). Adverse events of special interest grade ≥3 that occurred included ocular events (4.0% vs. 0%), peripheral neuropathy (5.6% vs. 0.4%), and bleeding events (2.4% vs. 2.9%, respectively). QoL was maintained in both groups however those in the chemotherapy group showed a trend toward decline, whereas those in the tisotumab vedotin group showed a trend toward improvement. The strengths of this study included its methodology and sample size, and the limitations included the follow-up time. Overall, this study found that tisotumab vedotin showed some greater efficacy and safety as a second or third-line therapy for patients with recurrent cervical cancer.
Click to read the study in NEJM
In-Depth [randomized controlled trial]: This multinational, open-label, phase III trial enrolled adults with recurrent or metastatic cervical cancer who progressed after standard-of-care (chemotherapy alone or with immunotherapy) and randomized them (1:1) into tisotumab vedotin (n=253), or investigator’s choice of chemotherapy (topotecan, vinorelbine, gemcitabine, irinotecan, or pemetrexed, n= 249). It was found that 80.5% of patient tumor samples had tumour expression of tissue factor. Median follow-up time was 10.8 months (95%CI, 10.3-11.6). Median OS was 11.5 months (95%CI, 9.8-14.9) in the tisotumab vedotin group and 9.5 months (95%CI, 7.9-10.7) in the chemotherapy group, with HR 0.70 (95%CI, 0.54-0.89, p=0.004). OS at 12 months was 48.7% (95%CI, 41.0-55.8) and 35.3% (95%CI, 28.0-42.7), respectively. Median PFS was 4.2 months (95%CI, 4.0-4.4) in the tisotumab vedotin group and 2.9 months (95%CI, 2.6-3.1) in the chemotherapy group, with an HR 0.67 (95%CI, 0.54-0.82, p<0.001). PFS at 6 months was 30.4% (95%CI, 24.5-36.5) and 18.9% (95%CI, 13.8-24.7), respectively. ORR was 17.8% (95%CI, 13.3-23.1) in the tisotumab vedotin group and 5.2% (95%CI, 2.8-8.8) in the chemotherapy group with an OR 4.0 (95%CI, 2.1-7.6, p<0.001). Median DoR was 5.3 months (95%CI, 4.2-8.3) in the tisotumab vedotin group and 5.7 months (95%CI, 2.8-NA) in the chemotherapy group. The median time to response was 1.6 months and 1.7 months, respectively. With regards to safety, grade ≥3 events occurred in 52.0% in the tisotumab vedotin group and 62.3% in the chemotherapy group, with the most common events being anemia (8.4% vs. 27.6%), urinary tract infection (4.4% vs. 7.1%), and neutropenia (3.6% vs. 13.4%, respectively). Adverse events of special interest grade ≥3 that occurred included ocular events (4.0% vs. 0%), peripheral neuropathy (5.6% vs. 0.4%), and bleeding events (2.4% vs. 2.9%, respectively). QoL was maintained in both groups however those in the chemotherapy group showed a trend toward decline, whereas those in the tisotumab vedotin group showed a trend toward improvement. Overall, this study found that tisotumab vedotin showed some greater efficacy and safety as a second or third-line therapy for patients with recurrent cervical cancer.
Image: PD
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