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which was presented at the European Society of Medical Oncology (ESMO) Congress 2023.
Median overall survival (OS) was 11.5 months among 253 women randomized to tisotumab vedotin (TV) monotherapy versus 9.5 months among 249 randomized to investigators’ choice of chemotherapy, a 30% reduction in the risk of death (P = .0038).
Median progression-free survival (PFS) was 4.2 months with TV versus 2.9 months with chemotherapy (P < .0001), but survival benefits were not statistically significant in a number of subgroups.
Nonetheless, “tisotumab vedotin should be considered as a potential new standard of care for patients who have progressed after first-line systemic therapy,” said lead investigator Ignace Vergote, MD, PhD, a gynecologic oncologist and researcher at the Catholic University of Leuven, Belgium, who presented the findings.
New and emerging options
The trial serves as the confirmation the Food and Drug Administration required when it gave TV accelerated approval in 2021 for recurrent or metastatic cervical cancer (r/m CC) that’s progressed during or after first-line treatment, an approval based on response rates in an earlier phase 2 trial, the InnovaTV 204 study.
TV is the only antibody-drug conjugate approved for the indication, but another agent is also under investigation, the anti-PD-1 cemiplimab. It’s not yet approved for r/m CC, but it is approved in the United States for locally advanced/metastatic basal cell carcinoma, cutaneous squamous cell carcinoma, and non–small cell lung cancer.
Cemiplimab outcomes were similar to TV’s in a phase 3 trial following progression on first-line treatment without anti-PD-1 therapy, with a median OS of 12 months with cemiplimab versus 8.5 months with investigators’ choice of chemotherapy.
Pembrolizumab is also approved as monotherapy for r/m CC for PD-L1 positive women after progression on or during first-line treatment based on response outcomes, not survival.
The question now is how to pick among the various options, said Krishnansu Tewari, MD, a gynecologic oncologist and researcher at the University of California, Irvine, who discussed InnovaTV 301 at the meeting.
In the second line for r/m CC, “we can hypothetically consider” TV monotherapy; pembrolizumab in PD-L1-positive women not previously exposed to a checkpoint inhibitor (CPI); cemiplimab in women not previously exposed to a CPI, and perhaps TV plus pembrolizumab, also in women new to CPIs.
It remains particularly unclear at the moment how to select between TV and cemiplimab monotherapy, if cemiplimab is approved for the indication.
One difference is that unlike in the cemiplimab trial, 28.1% of women treated with TV in the phase 3 trial had been on an anti-PD-(L)1 in the first line. However, although PFS benefits were statistically significant for TV after checkpoint inhibitor exposure, OS benefit was not.
Regarding cost, TV was administered at 2 mg/kg every 3 weeks in Innova; 40 mg costs around $7,000.
Cemiplimab was dosed at 350 mg every 3 weeks in its trial; a single dose costs over $10,000.
Subgroups fall short of statistical significance
In InnovaTV 301, 12-month OS was about 48.7% with TV versus 35% with chemotherapy; 6-month PFS was 30.4% with TV versus 18.9%.
The PFS benefit with TV did not reach statistical significance among the 35.2% of women who had not been treated with bevacizumab in the first-line, and there was no OS benefit or trend to benefit (HR 1.0) for them.
In addition to women previously treated with an anti-PD-1, OS benefits with TV were not statistically significant among the 54.2% of women with baseline performance scores of 0; the 36.8% with adeno or adenosquamous carcinoma, and the 62.8% who had been on one prior systemic regimen instead two.
Women in the trial were a median of 50 years old, and fewer than 7% were from the United States. Investigator choice of chemotherapy included topotecan, vinorelbine, gemcitabine, irinotecan, or pemetrexed.
The rate of grade 3 or higher adverse events was 29.2% with TV and 45.2% with chemotherapy.
The known side effects of TV were all higher than in the chemotherapy arm, including grade 3 or worse peripheral neuropathy (5.2%), ocular events (3.2%), and bleeding (0.8%).
The study was funded in part by Genmab and SeaGen, the companies co-developing TV. Dr. Vergote is an adviser to both companies and many others. Dr. Tewari is an adviser/consultant, researcher, and speaker for SeaGen and Genmab as well as for Merck, AstraZeneca, and other companies.
which was presented at the European Society of Medical Oncology (ESMO) Congress 2023.
Median overall survival (OS) was 11.5 months among 253 women randomized to tisotumab vedotin (TV) monotherapy versus 9.5 months among 249 randomized to investigators’ choice of chemotherapy, a 30% reduction in the risk of death (P = .0038).
Median progression-free survival (PFS) was 4.2 months with TV versus 2.9 months with chemotherapy (P < .0001), but survival benefits were not statistically significant in a number of subgroups.
Nonetheless, “tisotumab vedotin should be considered as a potential new standard of care for patients who have progressed after first-line systemic therapy,” said lead investigator Ignace Vergote, MD, PhD, a gynecologic oncologist and researcher at the Catholic University of Leuven, Belgium, who presented the findings.
New and emerging options
The trial serves as the confirmation the Food and Drug Administration required when it gave TV accelerated approval in 2021 for recurrent or metastatic cervical cancer (r/m CC) that’s progressed during or after first-line treatment, an approval based on response rates in an earlier phase 2 trial, the InnovaTV 204 study.
TV is the only antibody-drug conjugate approved for the indication, but another agent is also under investigation, the anti-PD-1 cemiplimab. It’s not yet approved for r/m CC, but it is approved in the United States for locally advanced/metastatic basal cell carcinoma, cutaneous squamous cell carcinoma, and non–small cell lung cancer.
Cemiplimab outcomes were similar to TV’s in a phase 3 trial following progression on first-line treatment without anti-PD-1 therapy, with a median OS of 12 months with cemiplimab versus 8.5 months with investigators’ choice of chemotherapy.
Pembrolizumab is also approved as monotherapy for r/m CC for PD-L1 positive women after progression on or during first-line treatment based on response outcomes, not survival.
The question now is how to pick among the various options, said Krishnansu Tewari, MD, a gynecologic oncologist and researcher at the University of California, Irvine, who discussed InnovaTV 301 at the meeting.
In the second line for r/m CC, “we can hypothetically consider” TV monotherapy; pembrolizumab in PD-L1-positive women not previously exposed to a checkpoint inhibitor (CPI); cemiplimab in women not previously exposed to a CPI, and perhaps TV plus pembrolizumab, also in women new to CPIs.
It remains particularly unclear at the moment how to select between TV and cemiplimab monotherapy, if cemiplimab is approved for the indication.
One difference is that unlike in the cemiplimab trial, 28.1% of women treated with TV in the phase 3 trial had been on an anti-PD-(L)1 in the first line. However, although PFS benefits were statistically significant for TV after checkpoint inhibitor exposure, OS benefit was not.
Regarding cost, TV was administered at 2 mg/kg every 3 weeks in Innova; 40 mg costs around $7,000.
Cemiplimab was dosed at 350 mg every 3 weeks in its trial; a single dose costs over $10,000.
Subgroups fall short of statistical significance
In InnovaTV 301, 12-month OS was about 48.7% with TV versus 35% with chemotherapy; 6-month PFS was 30.4% with TV versus 18.9%.
The PFS benefit with TV did not reach statistical significance among the 35.2% of women who had not been treated with bevacizumab in the first-line, and there was no OS benefit or trend to benefit (HR 1.0) for them.
In addition to women previously treated with an anti-PD-1, OS benefits with TV were not statistically significant among the 54.2% of women with baseline performance scores of 0; the 36.8% with adeno or adenosquamous carcinoma, and the 62.8% who had been on one prior systemic regimen instead two.
Women in the trial were a median of 50 years old, and fewer than 7% were from the United States. Investigator choice of chemotherapy included topotecan, vinorelbine, gemcitabine, irinotecan, or pemetrexed.
The rate of grade 3 or higher adverse events was 29.2% with TV and 45.2% with chemotherapy.
The known side effects of TV were all higher than in the chemotherapy arm, including grade 3 or worse peripheral neuropathy (5.2%), ocular events (3.2%), and bleeding (0.8%).
The study was funded in part by Genmab and SeaGen, the companies co-developing TV. Dr. Vergote is an adviser to both companies and many others. Dr. Tewari is an adviser/consultant, researcher, and speaker for SeaGen and Genmab as well as for Merck, AstraZeneca, and other companies.
which was presented at the European Society of Medical Oncology (ESMO) Congress 2023.
Median overall survival (OS) was 11.5 months among 253 women randomized to tisotumab vedotin (TV) monotherapy versus 9.5 months among 249 randomized to investigators’ choice of chemotherapy, a 30% reduction in the risk of death (P = .0038).
Median progression-free survival (PFS) was 4.2 months with TV versus 2.9 months with chemotherapy (P < .0001), but survival benefits were not statistically significant in a number of subgroups.
Nonetheless, “tisotumab vedotin should be considered as a potential new standard of care for patients who have progressed after first-line systemic therapy,” said lead investigator Ignace Vergote, MD, PhD, a gynecologic oncologist and researcher at the Catholic University of Leuven, Belgium, who presented the findings.
New and emerging options
The trial serves as the confirmation the Food and Drug Administration required when it gave TV accelerated approval in 2021 for recurrent or metastatic cervical cancer (r/m CC) that’s progressed during or after first-line treatment, an approval based on response rates in an earlier phase 2 trial, the InnovaTV 204 study.
TV is the only antibody-drug conjugate approved for the indication, but another agent is also under investigation, the anti-PD-1 cemiplimab. It’s not yet approved for r/m CC, but it is approved in the United States for locally advanced/metastatic basal cell carcinoma, cutaneous squamous cell carcinoma, and non–small cell lung cancer.
Cemiplimab outcomes were similar to TV’s in a phase 3 trial following progression on first-line treatment without anti-PD-1 therapy, with a median OS of 12 months with cemiplimab versus 8.5 months with investigators’ choice of chemotherapy.
Pembrolizumab is also approved as monotherapy for r/m CC for PD-L1 positive women after progression on or during first-line treatment based on response outcomes, not survival.
The question now is how to pick among the various options, said Krishnansu Tewari, MD, a gynecologic oncologist and researcher at the University of California, Irvine, who discussed InnovaTV 301 at the meeting.
In the second line for r/m CC, “we can hypothetically consider” TV monotherapy; pembrolizumab in PD-L1-positive women not previously exposed to a checkpoint inhibitor (CPI); cemiplimab in women not previously exposed to a CPI, and perhaps TV plus pembrolizumab, also in women new to CPIs.
It remains particularly unclear at the moment how to select between TV and cemiplimab monotherapy, if cemiplimab is approved for the indication.
One difference is that unlike in the cemiplimab trial, 28.1% of women treated with TV in the phase 3 trial had been on an anti-PD-(L)1 in the first line. However, although PFS benefits were statistically significant for TV after checkpoint inhibitor exposure, OS benefit was not.
Regarding cost, TV was administered at 2 mg/kg every 3 weeks in Innova; 40 mg costs around $7,000.
Cemiplimab was dosed at 350 mg every 3 weeks in its trial; a single dose costs over $10,000.
Subgroups fall short of statistical significance
In InnovaTV 301, 12-month OS was about 48.7% with TV versus 35% with chemotherapy; 6-month PFS was 30.4% with TV versus 18.9%.
The PFS benefit with TV did not reach statistical significance among the 35.2% of women who had not been treated with bevacizumab in the first-line, and there was no OS benefit or trend to benefit (HR 1.0) for them.
In addition to women previously treated with an anti-PD-1, OS benefits with TV were not statistically significant among the 54.2% of women with baseline performance scores of 0; the 36.8% with adeno or adenosquamous carcinoma, and the 62.8% who had been on one prior systemic regimen instead two.
Women in the trial were a median of 50 years old, and fewer than 7% were from the United States. Investigator choice of chemotherapy included topotecan, vinorelbine, gemcitabine, irinotecan, or pemetrexed.
The rate of grade 3 or higher adverse events was 29.2% with TV and 45.2% with chemotherapy.
The known side effects of TV were all higher than in the chemotherapy arm, including grade 3 or worse peripheral neuropathy (5.2%), ocular events (3.2%), and bleeding (0.8%).
The study was funded in part by Genmab and SeaGen, the companies co-developing TV. Dr. Vergote is an adviser to both companies and many others. Dr. Tewari is an adviser/consultant, researcher, and speaker for SeaGen and Genmab as well as for Merck, AstraZeneca, and other companies.
FROM ESMO 2023