Tivdak (tisotumab vedotin-tftv) reduced the risk for death by 30% compared with chemotherapy as second- or third-line therapy in patients with recurrent or metastatic cervical cancer with disease progression on doublet chemotherapy, as demonstrated in recent study findings.
Results from the phase 3 innovaTV 301/ENGOT-cx12/GOG-3057 trial that, which were presented at the 2023 ESMO Congress, showed that at a median follow-up of 10.8 months, the median overall survival (OS; the time from the start of treatment when a patient with cancer is still alive) was 11.5 months with Tivdak versus 9.5 months with chemotherapy. The 12-month OS rates were 48.7% and 35.3% with Tivdak and chemotherapy, respectively.
The median progression-free survival (PFS; the time during and after treatment when a patient with cancer is alive without disease worsening) was 4.2 months with Tivdak versus 2.9 months with chemotherapy. The 6-month PFS rates were 30.4% and 18.9% with Tivdak and chemotherapy, respectively.
“Based on these data, Tivdak should be considered a potential new standard of care for patients who have progressed after first-line systemic therapy,” lead study author Dr. Ignace B. Vergote said in a presentation of the data. Vergote is chairman of the Leuven Cancer Institute and head of the Department of Obstetrics and Gynecology and Gynecologic Oncology at the Catholic University of Leuven in Belgium.
Poor prognosis and high mortality are hallmarks of recurrent or metastatic cervical cancer, which represents the fourth most deadly cancer in women worldwide.
Although Keytruda (pembrolizumab) is approved for use in this population in the frontline setting in combination with chemotherapy, with or without Avastin (bevacizumab), patients who develop disease progression need improved therapeutic options.
Tivdak is an antibody-drug conjugate that was granted accelerated approval by the FDA in 2021 for patients with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy. The decision was based on findings from the single-arm innovaTV 204 trial, in which Tivdak led to an objective response rate (ORR; the percentage of patients with a partial or complete response to treatment) of 24% and a median duration of response (DOR) of 8.3 months.
To be eligible for enrollment in the phase 3 innovaTV 301 trial, patients had to have received a diagnosis of recurrent or metastatic cervical cancer; had documented disease progression on or after doublet chemotherapy with or without Avastin and an anti–PD(L)1 agent if eligible and available; and exposure to no more than two prior lines of therapy.
Patients were randomly assigned to Tivdak every 3 weeks (253 patients) or investigator’s choice of chemotherapy (249 patients), which could have included topotecan, vinorelbine, gemcitabine, irinotecan, or pemetrexed.
OS served as the primary end point. Secondary end points included PFS, ORR and safety.
A total of 660 patients were evaluated for eligibility and 502 patients were randomized. In the Tivdak and chemotherapy arms, respectively, 250 and 239 patients received at least 1 dose of their intended treatment. The most common reason for discontinuation in the Tivdak and chemotherapy arms, respectively, was disease progression (177 versus 193 patients), followed by an side effect (40 patients) in the Tivdak arm and patient decision in the chemotherapy arm (17 patients).
Only 21 patients in the Tivdak arm and 16 in the chemotherapy arm remain on study.
Baseline patient and disease characteristics were “very well balanced,” Ignace said, noting that most patients in the Tivdak and chemotherapy arms, respectively, had squamous cell carcinoma (63.2% versus 63.1%), extrapelvic metastatic disease (89.3% versus 90.4%), one prior line of systemic therapy (62.8% versus 59.8%), prior Avastin (64.8% versus 63.1%) and prior radiation therapy (81% versus 81.5%).
Additional findings indicated that the ORR was 17.8% with Tivdak versus 5.2% with chemotherapy. Best overall responses in the Tivdak arm included complete response (disappearance of all signs of cancer from treatment), partial response (decrease in tumor size from treatment), stable disease (cancer that is neither increasing nor decreasing in severity) and progressive disease (cancer that is spreading, growing or worsening); 5.9% of patients were not evaluable (NE). In the chemotherapy arm, best responses included only partial response (5.2%), stable disease (53%) and progressive disease (29.7%); 12% of patients were NE.
The disease control rate was 75.9% with Tivdak versus 58.2% with chemotherapy. The median DOR was 5.3 months and 5.7 months with Tivdak and chemotherapy, respectively.
The agent was well tolerated with a median relative dose intensity of 96.1% versus 90% with chemotherapy. Any-grade treatment-related side effects occurred in 87.6% of patients in the Tivdak arm and 85.4% of patients in the chemotherapy arm.
Two patients in the Tivdak arm and one patient in the chemotherapy died due to treatment-related side effects.
The most common treatment-related side effects with Tivdak and chemotherapy, respectively, were anemia (12.8% versus 43.9%), nausea (29.2% versus 36%), conjunctivitis (pink eye; 30.4% versus 0%), peripheral sensory neuropathy (nerve damage; 26.8% versus 2.1%), alopecia (hair loss; 24.4% versus 2.9%), epistaxis (nosebleed; 22.8% versus 2.1%), neutropenia (6.4% versus 21.8%), decreased appetite (18% versus 10%), diarrhea (16% versus 8.8%) and keratitis (inflammation of the cornea; 15.6% versus 0%).
Regarding side effects of special interest for Tivdak, only mild to severe side effects occurred, although the rates were significantly higher than with chemotherapy. These included ocular events, peripheral neuropathy and bleeding. Dose discontinuation due to ocular and peripheral neuropathy side effects were reported in 5.6% of patients in the Tivdak and chemotherapy arms, respectively.
Further breakdown of each category of event included reports of conjunctivitis (30.4%), keratitis (15.6%), dry eye (13.2%), peripheral sensory neuropathy (26.8%), paresthesia (burning or prickling in the arms, hands, feet or legs; 2.8%), muscular weakness (2.4%), peripheral sensorimotor neuropathy (2.4%), epistaxis (22.8%), hematuria (blood in the urine; 3.2%) and vaginal hemorrhage (3.2%).
“The safety profile of Tivdak was manageable and tolerable and consistent with previous experience,” Vergote concluded.
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