In the first article of a 2-part series, Shannon N. Westin, MD, MPH, looks at the promising responses to tisotumab vedotin for patients with recurrent or metastatic cervical cancer.
50-year-old Black woman busy with family, mother of college-aged children
Presenting Complaints: Dyspareunia and post-coital vaginal bleeding
New Diagnostic Workup:
Pembrolizumab (Keytruda) plus cisplatin/paclitaxel and bevacizumab (Avastin) was initiated at 6 cycles followed by an additional 6 cycles with pembrolizumab plus bevacizumab.
Targeted OncologyTM: What were the baseline characteristics of the patients in the phase 2 InnovaTV 204/GOG-3023/ENGOT-cx6 trial (NCT03438396) given tisotumab vedotin-tftv (Tivdak)?
WESTIN: There were low numbers of underrepresented minorities in this first study, unfortunately, where it was 95% White [patients], but it was otherwise reflective of the cervical cancer population as far as squamous cell carcinoma being the most common [diagnosis, followed by patients with] adenocarcinoma, and a few patients who had adenosquamous carcinoma.1 The majority of the patients had metastatic disease at baseline, so this was a measurable disease population.
Fifty-four percent of patients had gotten cisplatin with their radiation, while 70% had 1 prior line of therapy and the rest had 2 prior lines of [therapy]. Sixty-three percent had bevacizumab with their chemotherapy doublet up front, and this is an important number that a lot of people don't notice because this is a population that did poorly with their upfront regimen. Fifty-six percent did not have any benefit from their frontline regimen, and that's impressively [not good].
This was before the KEYNOTE-826 [NCT03635567] study, so the majority of [these patients] did not get the 4-drug regimen, but this is a population that [didn’t respond well to initial treatment]. I think that's important to note, because sometimes I feel like in our trial populations you can tell [the patients] had benefit from their last regimen, [and in this case they didn't], so you always want to make sure you know what you have.1
How did patients in this trial respond to treatment?
There was a 24% [confirmed] overall response rate and 7 patients had a complete response [CR].1 So this was exciting, [because it's] rare in the second-line cervical cancer population to see CRs to therapy. Seventeen percent had a partial response, and then a nice proportion of patients had a disease control rate of 72% [95% CI, 62.5%-80.7%]. This is important, because we always want to see a response to therapy...but for this population controlling [their] disease is important too.
If they're doing well, they're tolerating your treatment, and you can stabilize their disease, that's [great], too.... The median duration of response was 8.3 months [95% CI, 4.2–not reached], but you could have patients [that are on this treatment] for years. The median progression free-survival [PFS] was 4.2 months [95% CI, 3.2-4.6], the 6-month PFS rate was 34% [95% CI, 24.3%-43.1%], and the overall survival was pushing 12 months after study enrollment.1 These were the exciting data that led to the accelerated approval [of tisotumab vedotin by the FDA].2
Were these results seen across all patient subgroups in the trial?
The majority of patients had some benefit [on this therapy].1 There was shrinkage of the disease...and the majority of these patients are staying in that positive area where they're at least getting disease stabilization or reduction. In the subgroups, [the investigators] looked at things like their histology, whether patients had cisplatin treatment, their response to their last regimen, and their ECOG performance status.
Generally all [these subgroups favored tisotumab vedotin] from a response standpoint. They all showed a consistent response rate sitting around 20% to 30%. In fact, for some [of the observed subgroups] they still had a response to their last regimen, but a better chance of responding to this regimen. So, the positive prognostic factors were consistent in this patient population.1
1. Coleman RL, Lorusso D, Gennigens C, et al; innovaTV 204/GOG-3023/ENGOT-cx6 Collaborators. Efficacy and safety of tisotumab vedotin in previously treated recurrent or metastatic cervical cancer (innovaTV 204/GOG-3023/ENGOT-cx6): a multicentre, open-label, single-arm, phase 2 study. Lancet Oncol. 2021;22(5):609-619. doi:10.1016/S1470-2045(21)00056-5
2. FDA grants accelerated approval to tisotumab vedotin-tftv for recurrent or metastatic cervical cancer. News release. September 21, 2021. Accessed: September 25, 2023. https://tinyurl.com/bp9df42h