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MADRID -- Treatment with tisotumab vedotin (Tivdak) significantly extended overall survival (OS) compared with chemotherapy in patients with recurrent or metastatic cervical cancer, the phase III randomized innovaTV 301 study showed.

At a median follow-up of 10.8 months, patients treated with the antibody-drug conjugate had a median OS of 11.5 months compared with 9.5 months with investigator's choice of chemotherapy (HR 0.70, 95% CI 0.54-0.89, P=0.0038), reported Ignace Vergote, MD, PhD, of the Leuven Cancer Institute and Catholic University of Leuven in Belgium.

The 12-month OS rate was 48.7% with tisotumab vedotin versus 35.3% with chemotherapy, Vergote noted during a late-breaking presentation at the European Society for Medical Oncology (ESMO) annual congress.

There was also a consistent benefit in progression-free survival with tisotumab vedotin (4.2 vs 2.9 months; HR 0.67, 95% CI 0.54-0.82, P<0.0001) and confirmed objective response rate (17.8% vs 5.2%, respectively; OR 4.0, 95% CI 2.1-7.6, P<0.0001), with six complete responses.

"Based on these data, tisotumab vedotin should be considered a potential new standard of care for patients who have progressed after first-line systemic therapy," Vergote said.

Tisotumab vedotin is an antibody-drug conjugate composed of a tissue factor-directed human monoclonal antibody covalently linked to cytotoxic monomethyl auristatin E (MMAE). It was granted accelerated approval by the FDA for the treatment of adult patients with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy, based on results from the phase II innovaTV 204 trial.

The new study "is a practice-changing study," said ESMO-invited discussant Krishnansu Tewari, MD, of the University of California Irvine. "It's going to convert the accelerated approval of tisotumab vedotin in the United States to full approval, and importantly, it's going to introduce a brand new cervical cancer medicine to Europe."

During his discussion, Tewari posed several questions. For example, he pointed out that in the phase II innovaTV 204 study the objective response rate was 24%, but was lower in innovaTV 301, at 17.8%. "And these were both second- and third-line patients," he observed. "So, how different were these patients to account for that?"

He also wondered where tisotumab vedotin fits into the treatment paradigm for cervical cancer, noting that the drug has been combined with pembrolizumab (Keytruda), carboplatin, and bevacizumab (Avastin) in the study, which is due to be completed at the end of 2024. "Should it remain as a monotherapy option in the second-line setting? Or should it be moved to the first line?"

In this global, open-label, phase III study, 502 patients were randomized to either tisotumab vedotin or investigator's choice of topotecan, vinorelbine, gemcitabine, irinotecan, or pemetrexed. Median age was 50 years, and the two study arms were balanced for demographics and disease characteristics.

Of the patients, 63% in the tisotumab vedotin arm had one line of prior therapy, while 37% had two prior lines, compared with 60% and 40% in the chemotherapy arm, respectively; 64% of patients had prior bevacizumab, and 27.5% had prior anti-PD-1/L1 therapy.

The disease control rate was 75.9% with tisotumab vedotin compared with 58.2% with chemotherapy. Median duration of response was similar between the two groups (5.3 vs 5.7 months, respectively).

As for safety, rates of treatment-related adverse events (TRAEs) were similar in the two arms, but grade ≥3 TRAEs were more common in the chemotherapy group (45.2%) versus the tisotumab vedotin group (29.2%). Grade ≥3 TRAEs of special interest with tisotumab vedotin were peripheral neuropathy (5.2%), ocular events (3.2%), and bleeding events (0.8%).

Grade 5 TRAEs occurred in two patients in the tisotumab vedotin arm, and one patient in the chemotherapy arm.

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