A recent analysis showed that the human papillomavirus (HPV) vaccine was not associated with primary ovarian insufficiency, according to a new retrospective cohort from the Danish vaccination register.

Girls and women who received 4 doses (4HPV) of the vaccine showed no significant different in primary ovarian insufficiency compared with women who were unvaccinated.

The retrospective analysis followed 996,300 Danish girls and women from 2007 to 2016 between the ages 11 to 34 years. Half of the women (n = 505,829 [50.8%]) had received 4 HPV vaccine doses while the other half (n = 490,471 [49.2%]) were unvaccinated. Overall, 144 women were diagnosed with primary ovarian insufficiency, 54 of which had received 4 doses of the HPV vaccination. Moreover, the researchers determined that 26.94 years was the median age of diagnosis.

The adjusted hazard ratio comparing both vaccinated individuals and unvaccinated individuals who were diagnosed with primary ovarian insufficiency was 0.96 (95% CI, 0.55-1.68).

“The HPV vaccines are cancer-preventing vaccines, and, thus, the lackluster uptake in many countries is disheartening,” wrote Anders Hviid, DrMedSci, Statens Serum Institut and Emilia Theissen, MSc, University of Copenhagen, in a corresponding paper. “Our study provides much-needed support for the ovarian safety of the 4HPV vaccine, which is of key importance for clinical and public health personnel when addressing parental concerns about fertility issues associated with vaccination. There is currently little evidence for an association between 4HPV vaccination and primary ovarian insufficiency. On the contrary, the vaccine protects against infections that may decrease fertility.”

Estimate hazard ratios were measured through the cox proportional hazards regression and adjustments for age, calendar periods, and propensity scores summarized health care use. The investigation began in October 2020 and concluded in January 2021.

A 4HPV vaccine (Gardasil) was introduced to Danish childhood immunization schedules in January 2009. Previously, girls older than 12 years had been offered a 3-dose vaccine schedule. Starting in October 2008, girls between the ages of 13 to 15 were offered a “catch-up” vaccine. By August 2012, the “catchup” vaccine was also available to women between 20 and 27 years of age. In February of 2016, the 4-dose vaccine was replaced with a bivalent vaccine (Cervarix, GlaxoSmithKline).

The Danish vaccination register included information for both women who received their HPV vaccinations through the free national childhood immunization program, as well as for older individuals who were not eligible for the program and consequently purchased their vaccinations privately. Individuals who were vaccinated prior to the study’s start date were not included in the assessment.

The Danish National Patient Registry provided the data for primary ovarian insufficiency. Researchers used the diagnoses codes E28.3 and E28.31 to locate data for both primary ovarian hypofunction and premature menopause, respectively.

Primary outcomes were contacting hospitals for primary ovarian insufficiency and were measured through hazard ratios comparing vaccinated and unvaccinated individuals.

Receiving an HPV vaccination that was not a 4-dose vaccine was marked as a censoring event, as were diagnoses of cancer or carcinoma in situ, hypogonadism after ovarian treatment, or major surgical procedures on the genitalia.

As noted previously, the adjusted hazard ratio between vaccine and unvaccinated women was 0.96 (95% CI, 0.55-1.68). The HR did not change significantly in periods following the final vaccination, nor by age, or calendar period at first vaccination. Regarding propensity score, the adjusted HR was 0.58 (95% CI, 0.19-1.73) for the first, second, and third decile, 0.79 (95% CI, 0.35-1.80), for the fourth through the seventh decile, and 1.98, (95% CI, 0.71-5.56) for the eighth through tenth decile.

Forty-five individuals received a diagnosis of primary ovarian insufficiency which proceeded to be an amenorrhea or oligomenorrhea diagnosis. Researchers re-estimated the HR of these individuals and determined an adjusted HR of 1.32 (95% CI, 0.73-2.38). A further sensitivity analysis accounting for a lack of menarche data revealed an adjusted HR of 1.03 (95% CI, 0.58-1.83).

“The main strength of our study is the use of a nationwide cohort of girls and women with independent ascertainment of exposure and outcome status,” concluded the study authors. “Our study is the largest to date of 4HPV vaccination and primary ovarian insufficiency diagnosis, with 144 individuals, including 54 vaccinated individuals. It is the first, to our knowledge, to evaluate a composite outcome of oligomenorrhea and amenorrhea in a cohort study.”

The authors acknowledged certain limitations that merit consideration in future studies. First, researchers did not have access to the symptom onset date, and they speculated that there was likely delay between symptom onset and diagnosis. They also noted that individuals would likely be diagnosed with primary ovarian insufficiency beyond the years of the analysis.

Because the study did not include information on menarche, some of the younger individuals included in the analysis may not have been at risk during the allotted follow-up period. Finally, the study did not include information about oral contraceptive use, which may prolong time to or even decrease risk of primary ovarian insufficiency diagnosis. The authors acknowledged that this could potentially mask an increased rate.

Hviid A, Myrup Thiesson E. Association Between Human Papillomavirus Vaccination and Primary Ovarian Insufficiency in a Nationwide Cohort. 

 2021;4(8):e2120391. doi:10.1001/jamanetworkopen.2021.20391

Articles

A new retrospective cohort found that women who had received the human papillomavirus vaccine had similar rates of primary ovarian insufficiency as unvaccinated women.

Analysis Shows HPV Vaccine Not Associated with Infertility in Women 

Loop Electrical Excision Procedure (LEEP) was 40% more likely than cryotherapy to clear high-risk human papillomavirus (hrHPV) infections in women with cervical intraepithelial neoplasia (CIN2+), according to a secondary analysis of a randomized clinical trial in Kenya (

In addition, recurrent CIN was 5 times more likely than HPV to be associated with hrHPV detection.

Over a 24-month period, participants who underwent LEEP reported significantly higher hrHPV compared with cryotherapy recipients (HR, 1.40; 95% CI, 1.03-1.90; 

=.03). At the 12-month follow-up, a multivariable analysis revealed hrHPV type-specific persistence to be significantly associated with CIN2+ recurrence (adjusted hazard ratio, 4.70; 95% CI, 2.47 -8.95; 

 <.001). At 12 months, hrHPV testing for recurrent CIN2+ was 93% sensitivity, 46% specificity, 38% positive predictive value, and 95% negative predictive value.

“Cryotherapy is not as effective at clearing hrHPV because it may not achieve therapeutic depth compared with LEEP,” wrote Michael H. Chung, MD, MPH, Emory University, and study authors. “Unlike LEEP, cryotherapy does not excise tissue but causes necrosis through freezing up to a depth of 5 to 7 mm. Cervical dysplasia may be present in deeper tissue than cryotherapy can reach and may be infected with subclinical or latent hrHPV.”

The primary outcomes from this analysis were hrHPV positivity, which was defined as having 1 of 12 possible hrHPV types, (16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59) as well as disease recurrence, which meant a CIN grade 2 or higher with cervical biopsy.

Between June 2011 and September 2016, researchers screened 5,330 HIV- positive women through papanicolaou (PAP) testing. High-grade squamous intraepithelial lesions were found in 738 (13.8%) of the participants, and CIN 2+ subsequent colposcopy-directed biopsy was detected in 512 (9.6%) of participants.

The study included a total of 354 HIV-positive women with CIN2+. Among these participants, in the cryotherapy arm, median age was 37 years and baseline hrHPV prevalence was 90% (160 out of 177). In the LEEP arm, median age was 38 years and hrHPV prevalence was 94%. The randomized women received follow-ups every 6 months for 2 years, through hrHPV cervical swab and Pap test with cervical biopsy.

Between the 354 women with confirmed CIN2+ on colposcopy-directed biopsy as well as an hrHPV result at baseline testing, 177 women (50%) were treated with cryotherapy and 177 women (50%) were treated through LEEP. Sociodemographic and HIV characteristics were consistent between the two treatment groups; the average monthly household income was less than $150/month in both cohorts (62% vs 64%; P=.79) and immunocompromising was similar (CD4 count < 250 cells/mm3; 29% vs 27%; 

 = .75). In addition, the number of participants pretreated with ART for at least 2 years was comparable between the arms, (51% vs 57%; 

Researchers concluded that the results of the secondary analysis were consistent with those of the original clinical trial. LEEP has demonstrated clinical benefit over cryotherapy if and when this method is available and accessible in low-and middle-income countries. Testing for hrHPV following cervical treatment is potentially valuable in ruling out recurrent cervical disease among women living with HIV.

“These results correlate with the primary outcome analysis of the RCT, which demonstrated that LEEP was also better than cryotherapy in preventing recurrent CIN2+,” authors wrote. “Taken together, they demonstrate the superior treatment efficacy of LEEP over cryotherapy among women living with HIV.”

The study authors acknowledged a number of limitations. The first was that the secondary analysis assessed the findings of a trial conducted at a singular site in Kenya with 1 study clinician overseeing both the cryotherapy and LEEP procedures. Consequently, further research is needed to determine whether these study results extend to the rest of Kenya, or even other countries and regions.

Additionally, the study follow-up period was 2 years, which, according to the researchers, is too short a period to ascertain if hrHPV detection and CIN result in cervical cancer or mortality. This limitation is exacerbated by the fact that many participants were pretreated with ART, which might impact these outcomes. Future research should seek to extend the follow-up period to gain insight to the long-term implications of hrHPV persistence after treatment on cervical cancer and mortality among women living with HIV.

Chung MH, De Vuyst H, Greene SA, et al. Human papillomavirus persistence and association with recurrent cervical intraepithelial neoplasia after cryotherapy vs loop electrosurgical excision procedure among HIV-positive women. 

 August 5, 2021. Accessed September 8, 2021. doi:10.1001/jamaoncol.2021.2683

Loop electrical excision procedure (LEEP) demonstrated superior capabilities in clearing high-risk HPV infections in women with cervical intraepithelial neoplasia (CIN2+).

Loop Electrical Excision Procedure Superior to Cryotherapy in Clearing High-Risk HPV Infections 

The FDA has granted priority review to cemiplimab-rwlc (Libtayo) in response to the supplemental biologics license application (sBLA) on the indication of recurrent or metastatic cervical cancer whose disease progressed on or after chemotherapy.

The priority review is based off findings from the open-label, multi-center phase 3 EMPOWER-Cervical 1 trial, which is the largest randomized clinical trial in advanced cervical cancer to-date. Updated findings presented at the 2021 ESMO Virtual Plenary revealed that cemiplimab demonstrated superior overall survival (OS), progression-free survival (PFS), and objective response rate (ORR), compared with chemotherapy, as an advanced cervical cancer therapy. 

The FDA set a target action date of January 30, 2022.

Overall, the 304 participants treated with cemiplimab–a fully human monoclonal antibody that functions by targeting the PD-L1 immune checkpoint receptor on T-cells–experienced a 31% reduced risk of mortality (HR, 0.69; 95% CI, 0.56-0.84; 

 = .00011), a 25% reduced risk of disease progression (HR, 0.75; 95% CI, 0.63 -0.89; 

 = .00048), and an ORR of 16% compared with 6% with chemotherapy (95% CI, 13%-21%; 

"In this phase 3 trial, Libtayo demonstrated a significant improvement in overall survival in women with advanced cervical cancer after progression on chemotherapy, reducing the risk of death by 31% compared to chemotherapy in the overall population," said trial investigator Krishnansu S. Tewari, MD, professor and director of the Division of Gynecologic Oncology at the University of California, Irvine. "Improvements in progression-free survival and objective response rate were also demonstrated in the overall population compared to chemotherapy. Taken together, this landmark trial–which enrolled patients regardless of PD-L1 expression status–helps support the use of Libtayo as a potential new second-line treatment for women with advanced cervical cancer who face a poor prognosis and limited treatment options."

The study assessed women with recurrent or metastatic cervical cancer whose disease had progressed beyond platinum-based chemotherapy. PD-L1 expression status was not a factor in participant eligibility. Women from 14 countries participated in the trial, including the U.S., Japan, Taiwan, South Korea, Canada, Russia, Poland, Spain, Brazil, Australia, the UK, Italy, Greece and Belgium. Seventy-eight percent of patients had squamous cell carcinoma (SCC) and 22% had adenosquamous carcinoma.

In addition, a smaller subset of patients in the trial whose disease was identified as SCC experienced positive results with cemiplimab compared with chemotherapy. These 238 patients experienced a 27% reduced risk of mortality (HR, 0.73; 95% CI, 0.58-0.91; 

 = .00306), a 29% reduced risk of disease progression (HR, 0.71; 95% CI, 0.58 -0.86; 

 = .00026), and an ORR of 18% compared with 7% with chemotherapy (95% CI, 13%-23%).

A post-hoc analysis also determined that the 65 patients with adenocarcinoma experienced a 44% reduced risk of mortality (HR, 0.56; 95% CI, 0.36-0.85; 

 < .005), a 9% reduced risk of disease progression (HR, 0.91; 95% CI, 0.62-1.34), and an ORR of 12% compared with 5% with chemotherapy (95% CI, 1%-13%).

Notably, findings also determined that patients treated with the novel regimen experienced a superior global health status/quality of life (GHS/QoL) than those treated with chemotherapy. The change in status became clinically meaningful starting at cycle 8, with the improvement with cemiplimab being 1.01 and the worsening for chemotherapy being -6.81 (95% CI).

Investigators reported no new safety signals. Adverse events (AEs) occurred in 88% of participants in the experimental arm and 91% of the control arm. Common AEs included anemia (25% vs 45%, respectively), nausea (18% vs 33%), fatigue (17% vs 16%), vomiting, (16% vs 23%), decreased appetite (18% vs 33%), and constipation (15% vs 20%).

AEs with a grade 3 or higher severity occurred in 45% of patients receiving cemiplimab and 53% of patients receiving chemotherapy. These AEs included asthenia (2% vs 1%, respectively), and pyrexia (less than 1% vs 0%). In addition, immune-related were observed in 16% of patients receiving cemiplimab and in less than 1% of patients on chemotherapy.

Discontinuations were necessary among 8% of patients in the experimental cohort and in 5% of the control cohort.

Providers should ask their patients about any immune-related problems, organ transplant history, allogeneic stem cell transplant history, or nervous system conditions, before prescribing cemiplimab, as those factors may influence the suitability of the drug.

FDA accepts libtayo (cemiplimab-rwlc) for priority review for advanced cervical cancer. Regeneron. Press release. September 28, 2021.

Positive phase 3 libtayo (cemiplimab) results in advanced cervical cancer presented at ESMO virtual plenary. Regeneron. News release. May 12, 2021. Accessed September 28, 2021. 

https://newsroom.regeneron.com/news-releases/news-release-details/positive-phase-3-libtayor-cemiplimab-results-advanced-cervical

The FDA has granted cemiplimab-rwlc a priority review based on findings from the largest to-date, randomized clinical trial in advanced cervical cancer. 

FDA Grants Priority Review to Cemiplimab for Advanced Cervical Cancer

Impressive response rates, duration of response (DOR) and overall survival were all observed in pretreated patients with recurrent/metastatic cervical cancer who were administered a combination of the anti-PD-1 antibody balstilimab and the anti-CTLA-4 antibody zalifrelimab (AGEN1884) in a single arm phase 2 trial (NCT03495882) recently presented at the 2021 ESMO Annual Congress.

Among the 125-patient efficacy evaluable population, the combination elicited an overall response rate (ORR) of 25.6%. Ten (8.8%) responders experienced a complete response (CR). Among the 67-patients with a positive PD-L1 status, the ORR was 32.8% compared with 9.1% in the PD-L1-negative subgroup (n = 33).

Notably, the median duration of response (DOR) was not reached (range, 9.3 months-not reached). The 6-month DOR rate was 86.4% and the 12-month rate was 66.7%.

“There remains a significant unmet medical need for patients with recurrent or metastatic cervical cancer who progress after platinum-containing chemotherapy,” explained David O'Malley, MD, the director of the Division of Gynecologic Oncology at The Ohio State University Comprehensive Cancer Center–Arthur G. James Cancer Hospital and Richard J. Solove Research Institute and a professor in the Department of Obstetrics and Gynecology at The Ohio State University College of Medicine in Columbus.

“We know that single agent PD-1 activity is modest while CTLA-4 inhibition demonstrates limited to no activity in patients with cervical cancer,” he added. “Combining anti-PD1 and anti-CTLA-4 [agents] is now an established treatment paradigm across a broad spectrum of solid tumors. In this phase 2 study design, we report the largest trial to date combining PD-1 and CTLA-4 in patients with cervical cancer.”

In order to be eligible for the trial, patients needed to have histologically confirmed squamous cell carcinoma, adenosquamous carcinoma, or adenocarcinoma of the cervix that relapsed after platinum-based treatment. Patients also had to have measurable disease and an ECOG performance status of 0 or 1.

The primary end point of the trial was ORR by RECIST v1.1 per an independent review committee. Secondary end points included OS, DOR, and progression-free survival. The trial enrolled a total of 155 patients in Europe, Australia, South America, and the United States.

The median age of the total population was 50 (range, 24-76). Most patients (70.3%) had squamous cell carcinoma, 27.1% had adenocarcinoma, and 2.6% had adenosquamous histology.ECOG performance status was well balanced, 57.4% registered a 0 and 42.6% were at 1. A majority of patients (56.8%) had positive PD-L1 tumor expression status, defined as a combined positive score of at least 1%. The most common prior therapy exposures, besides platinum-containing (99.4%), were taxane (78.7%) and bevacizumab (32.9%).

Balstilimab was administered at a dose of 3 mg/kg every 2 weeks. Zalifrelimab 1 mg/kg was given every 6 weeks. Treatment lasted for up to 24 months and follow-up imaging occurred every 6 weeks through 2 years.

At a median follow-up of 21 months, the median PFS was 2.7 months (95% CI, 1.5-3.7). The median OS was 12.8 months (95% CI, 8.8-17.6). In the PD-L1-positive subset, the median OS improved to 15.7 months (95% CI, 7.6-21.1).

“The response rates [for this combination] nearly double currently achieved with approved agents in the second-line setting, including single agent PD-1 antibodies,” noted O’Malley. “Beyond response rate, the distinguishing feature of combining CTLA-4 and PD-1 antibodies are improved depth and durability of responses as well as survival outcomes. Longer follow-up will hopefully confirm this exciting trend and establish long-term survival as an achievable goal in advanced/recurrent cervical cancer.”

In terms of safety, 71.0% of the 155-patient safety population experienced a treatment-related adverse event (TRAE) of any grade. Common TRAEs of any grade included hypothyroidism (16.8%), diarrhea (14.2%), and fatigue (11.6%). TRAEs of at least grade 3 occurred in 20.0% of patients and included increased alanine transaminase (2.6%) and diarrhea (1.9%). TRAEs that lead to dose interruption were reported in 12.3% of patients and TRAEs leading to dose discontinuation occurred in 7.7% of patients.

Immune-mediated AEs were less commonly observed (44.5%), and included hypothyroidism (14.2%), hyperthyroidism (7.1%), diarrhea (7.1%), and puritis (4.5%).

“[This was] the largest study to date evaluating dual PD-1/CTLA-4 checkpoint blockade in patients with recurrent/metastatic cervical cancer,” concluded O’Malley. “With a median follow-up of almost 2 years, the balstilimab and zalifrelimab combination showed high response rates, durable clinical activity, and promising overall survival results. Advocacy outcomes were particularly impressive in the PD-L1 positive patients, but also broadly seen in subgroups with poor risk features. A confirmatory randomized phase 2 study comparing balstilimab and zalifrelimab with balstilimab alone is actively enrolling.”

O’Malley DM, Neffa M, Monk BJ, et al. Balstilimab (anti-PD-1) in combination with zalifrelimab (anti-CTLA-4): Final results from a phase II study in patients (pts) with recurrent/metastatic (R/M) cervical cancer (CC). Presented at: 2021 European Society for Medical Oncology Congress. September 16-21, 2021; virtual. Abstr 724MO.

A phase 2 trial presented at the 2021 ESMO Annual Congress showed that Balstilimab plus Zalifrelimab induced superior response rates, duration of responses, and overall survival in patients with recurrent/metastatic cervical cancer. 

Balstilimab Zalifrelimab Combination Yields Promising Results in Recurrent/Metastatic Cervical Cancer

Adding pembrolizumab (Keytruda) to chemotherapy with or without bevacizumab (Avastin) proved to effectively improve survival rates and invoke responses in patients with recurrent, or metastatic cervical cancer in the phase 3 KEYNOTE-826 trial (NCT036355667). Data from the trial’s first interim analysis were presented as part of the Presidential Symposium during the 

In the subset of patients with a PD-L1 combined positive score (CPS) of 1 or higher, the median progression-free survival (PFS) in the investigative and control arms was 10.4 months (95% CI, 9.7-12.3) vs 8.2 months (95% CI, 6.3-8.5), respectively (HR, 0.62; 95% CI, 0.50-0.77; 

< .001). In this group, the median overall survival (OS) was not reached (NR) at the time of the data cutoff in the investigative arm (95% CI, 19.8–NR) vs 16.3 months (95% CI, 14.5-19.4) in the control arm (HR, 0.64; 95% CI, 0.50-0.81; 

In the all-comer population, the median PFS was 10.4 months (95% CI, 9.1-12.1) in the investigative arm vs 8.2 months (95% CI, 6.4-8.4) in the control arm (HR, 0.65; 95% CI, 0.53-0.79; 

< .001). The median OS in this population was 24.4 months (19.2–NR) with pembrolizumab vs 16.5 months (95% CI, 14.5-19.4) with placebo (HR, 0.67; 95% CI, 0.54-0.84; 

In the group of patients who had a PD-L1 CPS of 10 or higher, the median PFS with pembrolizumab plus chemotherapy with or without bevacizumab was 10.4 months (95% CI, 8.9-15.1) vs 8.1 months (95% CI, 6.2-8.8) with chemotherapy with or without bevacizumab (HR, 0.58; 95% CI, 0.44-0.77; 

< .001). The median OS was also NR (95% CI, 19.1-NR) in the investigative arm vs 16.4 months (95% CI, 14.0-25.0) in the control arm (HR, 0.61; 95% CI, 0.44-0.84; 

“Adding pembrolizumab to chemotherapy with or without bevacizumab provides statistically significant, clinically meaningful improvements in PFS and OS in patients with persistent, recurrent, or metastatic cervical cancer. The significant benefit was observed in all primary analysis populations and was generally consistent across protocol-specified subgroups,” lead study author Nicoletta Colombo, MD, PhD, director of the Gynecologic Oncology Division at the European Institute of Oncology and associate professor of Obstetrics and Gynecology at the University of Milan-Bicocca in Milan, Italy, said in a presentation of the findings. “Overall, data from KEYNOTE-826 suggest that pembrolizumab plus platinum-based chemotherapy with or without bevacizumab may be a new first-line standard of care for the treatment [of these patients].”

Platinum-based chemotherapy has served as standard treatment for patients with persistent, recurrent, or metastatic cervical cancer, with the preferred regimen being platinum, paclitaxel, and bevacizumab. Although PD-1 inhibitors, such as pembrolizumab and cemiplimab (Libtayo), have previously demonstrated efficacy in patients with previously treated cervical cancer, no data are available to indicate whether the addition of a PD-L1 inhibitor to chemotherapy with or without bevacizumab would improve outcomes.

To this end, investigators launched the double-blind KEYNOTE-826 trial, which enrolled patients with persistent, recurrent, or metastatic cervical cancer that was not amenable to curative treatment.

Eligible patients needed to have an ECOG performance status of 0 or 1 and could not have previously received systemic chemotherapy. However, prior radiotherapy and chemoradiotherapy was allowed.

A total of 617 participants were randomized 1:1 to receive intravenous (IV) pembrolizumab at 200 mg every 3 weeks for up to 35 cycles plus paclitaxel and cisplatin or carboplatin every 3 weeks for up to 6 cycles with or without IV bevacizumab at 15 mg/kg every 3 weeks (n = 308) or placebo plus chemotherapy with or without bevacizumab at the same dose and schedule (n = 309).

Stratification factors included metastatic disease at diagnosis (yes vs no), PD-L1 CPS (<1 vs 1 to <10 vs ≥10), and planned bevacizumab use (yes vs no).

The dual primary end points of the study were investigator-assessed OS and PFS per RECIST v1.1 criteria; key secondary end points comprised overall response rate (ORR), duration of response (DOR), 12-month PFS, and safety. Patient-reported outcomes (PROs) were evaluated using the EuroQoL EQ-5D-5L Visual Analog Scale (VAS) score and served as an exploratory end point.

The PFS and OS benefit of adding pembrolizumab were evaluated sequentially in 3 patient populations: those with PD-L1 CPS of 1 or higher, all comers, and those with a PD-L1 CPS of 10 or higher. The overall alpha was controlled at one-sided 2.5% across the 6 primary hypotheses and all planned analysis. The statistical analysis plan permits 2 interim analyses prior to a final analysis.

The first interim analysis was planned to occur when approximately 370 events of disease progression or death were reported in the population of patients with a PD-L1 CPS of 1 or higher. At that time, all primary hypotheses were to be tested, noted Colombo.

As of a data cutoff of May 3, 2021, 307 patients on the investigative arm and 309 patients on the control arm received treatment.

“The median follow-up duration was almost 3 years, and approximately twice as many patients in the pembrolizumab arm remain on, or have completed, study treatment,” Colombo said.

Baseline characteristics in the all-comer and PD-L1 CPS subsets were well balanced between the 2 treatment arms, Colombo added.

Among the all-comer population, the median age between the arms was 50.5 years (range, 22-82). Moreover, 43.3% of patients had an ECOG performance status of 1, 72.3% had squamous cell disease, and 48.3% had previously received chemoradiation or radiation.

At initial diagnosis, 30.8% of patients had stage IVB disease, and 19.8% had metastatic disease at the time of study entry. Regarding PD-L1 status, 51.4% of patients had a CPS of 10 or higher, 37.4% had a CPS between 1 and 10, and 11.2% had a CPS of less than 1. Bevacizumab was used in 63.1% of patients during the study.

Additional data reported during the meeting showed that the 12-month PFS rates in the investigative and control arms within the subset of patients with a PD-L1 CPS of 1 or higher were 45.5% (95% CI, 39.2%-51.5%) and 34.1% (95% CI, 28.3%-40.0%), respectively. In the all-comer population, these rates were 44.7% (95% CI, 38.8%-50.4%) and 33.5% (95% CI, 28.0%-39.1%), respectively. Lastly, in the subset of patients with a PD-L1 CPS of 10 or higher, these rates were 44.6% (95% CI, 36.3%-52.5%) and 33.5% (95% CI, 25.9%-41.2%), respectively.

“The benefit of adding pembrolizumab was generally consistent across the protocol-specified subgroups, with all HRs favoring the pembrolizumab arm and all 95% CIs overlapping,” Colombo said.

The OS benefit of adding pembrolizumab was generally consistent across all protocol-specified subgroups. Notably, the HR favored the addition of pembrolizumab in both bevacizumab subgroups, suggesting that the addition of the immunotherapy to chemotherapy provides benefit irrespective of whether patients can receive bevacizumab, Colombo said.

“The relative OS benefit observed in the pembrolizumab arm appeared to increase with increasing PD-L1 expression and the HR for the PD-L1–negative population was 1.00,” Colombo added. “But, given the relatively small sample size of this subgroup and the overall study design, robust conclusions regarding the efficacy of pembrolizumab plus chemotherapy with or without bevacizumab in patients with PD-L1–negative tumors cannot be drawn.”

The addition of pembrolizumab to chemotherapy with or without bevacizumab also improved ORRs vs placebo plus chemotherapy with or without bevacizumab across the 3 primary analysis populations.

In the subset of patients with a PD-L1 CPS of 1 or higher, the ORR in the investigative arm was 68.1% (95% CI, 62.2%-73.6%) vs 50.2% (95% CI, 44.1%-56.2%) in the control arm, with a median duration of response (DOR) of 18.0 months (range, 1.3+ to 24.2+) vs 10.4 months (range, 1.5+ to 22.0+), respectively.

In the all-comer population, the ORRs were 65.9% (95% CI, 60.3%-71.2%) vs 50.8% (95% CI, 45.1%-56.5%), respectively, with the same median DORs as were reported in the PD-L1 CPS of 1 or higher subset. Lastly, in the group of patients with a PD-L1 CPS of 10 or higher, the ORRs were 69.6% (95% CI, 61.8%-76.7%) vs 49.1% (95% CI, 41.1%-57.1%), respectively, with median DORs of 21.1 months (range, 1.3+ to 24.2+) vs 9.4 months (range, 2.1+ to 21.5+), respectively.

Investigators collected information on PROs throughout treatment on the trial. Time to deterioration in the EQ-5D-5L VAS score was improved on the pembrolizumab arm, with a HR of 0.75 (95% CI, 0.58-0.97). According to Colombo, the median time to deterioration was not reached in the investigative arm vs 7.7 months in the control arm.

The safety profile of the pembrolizumab regimen was manageable. The incidence of all-cause and treatment-related grade 3 or higher or serious adverse effects (AEs) were all numerically greater in the immunotherapy-containing arm, but patients receiving pembrolizumab were generally on treatment longer vs those receiving placebo, according to Colombo.

“Approximately one-third of patients on the pembrolizumab arm discontinued any treatment component due to an AE,” Colombo said. “The incidence of AEs leading to death were similar in the treatment arms. As expected, the incidence of immune-related AEs was higher in the pembrolizumab arm.”

The most frequent all-cause AEs reported on the investigative and control arms included anemia (61.2% vs 53.4%, respectively), alopecia (56.4% vs 57.9%), nausea (39.7% vs 43.7%), diarrhea (35.5% vs 29.8%) and fatigue (28.7% vs 27.2%), among others. The most common immune-mediated AEs were hypothyroidism (18.2% vs 9.1%) and hyperthyroidism (7.5% vs 2.9%).

Colombo N, Dubot C, Lorusso D, et al. Pembrolizumab plus chemotherapy versus placebo plus chemotherapy for persistent, recurrent, or metastatic cervical cancer: randomized, double-blind, phase 3 KEYNOTE-826 study. Presented at: 2021 ESMO Congress; September 16-21, 2021; virtual. Abstract LBA2_PR

Data presented at the 2021 ESMO Congress suggest that pembrolizumab in addition to chemo with or without bevacizumab may become new standard of care in the frontline setting of cervical cancer treatment.

Pembrolizumab in Addition to Chemo Holds Potential as New SOC in Cervical Cancer Frontline Setting

Rechallenging olaparib (Lynparza) as a maintenance therapy in heavily pretreated patients with relapsed ovarian cancer following response to platinum-based chemotherapy significantly improved progression-free survival (PFS), regardless of 

 status, according to data from the phase 3 OReO/ENGOT Ov-38 (NCT03106987) study presented during the 2021 ESMO Congress.

Data showed that the median PFS improved from 2.8 months in patients who received placebo to 4.3 months in those randomized to rechallenge with olaparib among the cohort of patients with 

-mutant ovarian cancer (HR, 0.57; 95% CI, 0.37-0.87; 

-mutant cohort, the median PFS improved similarly with olaparib rechallenge from 2.8 months in the placebo arm to 5.3 months in the olaparib arm (HR, 0.43; 95% CI, 0.26-0.71; 

The data are the first to demonstrate a benefit to PARP inhibitor rechallenge in patients with platinum-sensitive relapsed ovarian cancer, said Eric Pujade-Lauraine, MD, PhD, of ARCAGY-GINECO in Paris, France, in a virtual presentation during the meeting.

-mutant cohorts, a proportion of patients derived clinically relevant long-term benefit from maintenance olaparib rechallenge,” he said.

Although most patients with newly diagnosed or platinum-sensitive relapsed ovarian cancer achieve long-term responses to PARP inhibitors as maintenance therapy, the majority of them will relapse. It has been unknown whether patients who relapse on PARP inhibition will have a benefit from rechallenged PARP inhibitor therapy following responde to platinum-based chemotherapy.

OReO/ENGOT Ov-38 is a phase 3, randomized, double-blind trial that enrolled 220 patients with nonmucinous platinum-sensitive relapsed ovarian cancer who received 1 prior line of PARP inhibitor maintenance and were in response to their most recent platinum-based chemotherapy. Two cohorts were enrolled, a 

-mutant cohort (n = 108), both of which were randomized 2:1 to olaparib at 300 mg (or 250 mg if 300 mg was not previously tolerated) or placebo until progression.

Eligible patients must have had a complete response (CR) or partial response to their most recent platinum regimen or no evidence of disease after surgery without a rise in their CA-125 level. The 

-mutant cohort must have had prior PARP inhibitor exposure for at least 18 months after first-line chemotherapy, or at least 12 months after second-line or later chemotherapy. For the non–

-mutant cohort, prior PARP inhibitor exposure for at least 12 months after frontline chemotherapy or at least 6 months after second- or later-line chemotherapy was required.

Patients were stratified by prior bevacizumab (Avastin) and 3 or fewer or at least 4 prior lines of platinum-based chemotherapy. The primary end point was investigator-assessed PFS; secondary end points were time to RECIST/CA-125 progression or death, time to first and second subsequent therapy or death, time to treatment discontinuation or death, overall survival, health-related quality of life, and safety.

-mutant cohort, the median age was 58.5 years (range, 37-80) in the olaparib arm and 61.5 years (range, 44-87) in the placebo arm. Forty-two percent of patients in each arm had 3 prior lines of any chemotherapy, and 23% and 21% in the olaparib and placebo arms, respectively, had exposure to more than 4 prior lines. Thirty-five percent of the olaparib arm and 42% of the placebo arm had exposure to more than 4 prior lines of platinum-based chemotherapy. The best response to platinum-based chemotherapy prior to study entry was a CR in 20% and 34% of the olaparib and placebo arms, respectively.

-mutant cohort, the median age was 66.5 years (range, 29-81) in the olaparib arm and 62.5 years (range, 43-77) in the placebo arm. Twenty-eight percent and 22%, respectively, had more than 4 lines of any prior chemotherapy, and 32% and 31%, respectively, had at least 4 prior lines of platinum-based chemotherapy. Best response to platinum-based chemotherapy prior to study entry was a CR in 26% of the olaparib group and 31% of the placebo group.

The median duration range of prior PARP inhibitor therapy was 18.3 to 21.2 months in the 

-mutant cohort and 12.4 to 12.6 months in the non–

-mutant cohort. Sixty-one percent of the 

-mutant cohort had a duration of prior PARP inhibitor exposure of at least 18 months, and 53% to 57% of the non–

-mutant cohort had a duration of prior PARP inhibitor exposure of at least 12 months.

-mutant cohort was olaparib (91% vs 21.5%, respectively), niraparib (Zejula; 4.5% vs 61%), rucaparib (Rubraca; 3% vs 13.5%), veliparib (0% vs 2%), blinded therapy (0% vs 3.5%), and placebo (1.5% in each).

Homologous recombination deficiency (HRD) status was positive in about 40% of the non–

-mutant cohort, with HRD status unknown in up to one quarter of patients in this cohort.

-mutant cohort, treatment is ongoing in 9% of patients on the olaparib arm and 3% of the placebo arm; in the non–

-mutant cohort, these percentages are 29% and 17%, respectively. About 60% of patients on the 

-mutant cohort discontinued the study, 90% of which were due to death. Twenty-eight percent of those in the non–

-mutant cohort discontinued, with 67% (olaparib arm) and 73% (placebo arm) discontinuing due to death.

“A proportion of patients derived long-term benefit in the olaparib arm,” said Pujade-Lauraine, as the PFS rates in the 

-mutant cohort at 12 months after randomization were 19% in the olaparib arm vs 0% in the placebo arm.

-mutant cohort, “long-term benefit was again observed—14% of patients in the olaparib arm being free of disease progression [at 12 months] vs 0% in the placebo arm,” he added. In exploratory analyses, the benefit of olaparib in the non–

-mutant cohort appeared consistent, irrespective of HRD status.

In both cohorts, the PFS benefit to olaparib was observed across subgroups, and was irrespective of HRD status. No new safety signals were observed and the rate of discontinuations due to adverse events was low, said Pujade-Lauraine.

Clare L. Scott, MBBS, PhD, chair of Gynecological Cancer at University of Melbourne, Australia, who served as a discussant on the abstract, said that the results from OReO/ENGOT Ov-38 provide some rules to identify patients who would benefit based on prior PARP inhibitor exposure.

“All clinical groups appear to benefit except for patients who had a short time on treatment prior to coming on to study, but really we need to define the molecular groups who benefit from alternative therapies or combination PARP inhibitor therapies,” Scott said.

Pujade-Lauraine E, Selle F, Scambia G, et al. Maintenance olaparib rechallenge in patients (pts) with ovarian carcinoma (OC) previously treated with a PARP inhibitor (PARPi): phase IIIb OReO/ENGOT Ov-38 trial. Presented at: 2021 ESMO Congress; September 16-21, 2021; virtual. Abstract LBA33.

Rechallenge with maintenance olaparib following response to platinum-based chemotherapy significantly improved PFS in heavily pretreated patients with relapsed ovarian cancer.

Rechallenge With Olaparib Maintenance Improves PFS in Heavily Pretreated Ovarian Cancer

Tisotumab vedotin (Tivdak) received accelerated approval from the FDA for the treatment of adult patients with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy.

The regulatory decision is based on data from phase 2 innovaTV 204 trial (NCT03438396), in which the antibody-drug conjugate elicited an objective response rate (ORR) of 24% (95% CI, 15.9%-33.3%) per independent review committee using RECIST v1.1 criteria in patients with recurrent or metastatic cervical cancer who received prior doublet chemotherapy and bevacizumab (Avastin).

Among those who responded to treatment, 7% experienced a complete response and 17% had a partial response. The median duration of response with tisotumab vedotin was 8.3 months (95% CI, 4.2–not reached). The median time to response (TTR) with the ADC was 1.4 months (range, 1.1-5.1), and activity was noted within the first 2 treatment cycles.

“Once recurrent or metastatic cervical cancer progresses, there is a need for more options for these patients,” said Robert L. Coleman, MD, chief scientific officer, US Oncology Research and lead investigator of the innovaTV 204 clinical trial, stated in a press release. “This is an important development for patients with recurrent or metastatic cervical cancer.”

The single-arm, multicenter, phase 2 innova TV 204 trial enrolled a total of 101 previously treated patients with recurrent and/or metastatic cervical cancer who were intravenously administered tisotumab vedotin at a dose of 2.0 mg/kg every 3 weeks until disease progression or unacceptable toxicity.

To be eligible for enrollment, patients had to have recurrent or extrapelvic metastatic disease, experienced disease progression during or after doublet chemotherapy with bevacizumab (if eligible), had received 2 or fewer prior systemic therapies, and have had an ECOG performance status of 0 to 1.

The primary end point of the trial was ORR per RECIST v1.1 criteria and independent imaging review committee (IRC) assessment. Secondary end points included ORR per investigator assessment and RECIST criteria, overall survival (OS), and safety.

DOR, TTR, and progression-free survival (PFS) per IRC and investigator, served as additional end points. Investigators also evaluated biomarkers and health-related quality of life with the treatment.

The median age of study participants was 50 years, 95% were White, and 58% had an ECOG performance status of 0. Moreover, 68% of patients had squamous cell carcinoma, 27% had adenocarcinoma, and 5% had adenosquamous carcinoma. Almost all patients, or 94%, had extrapelvic metastatic disease at baseline.

Fifty-four percent of participants had received prior cisplatin plus radiation therapy and 70% had received 1 prior line of systemic treatment for recurrent or metastatic disease. Additionally, 63% of patients received prior bevacizumab and doublet chemotherapy as first-line treatment and 56% did not respond to their last systemic treatment received.

Patients received treatment for a median duration of 4.2 months at a median of 6 doses; a high dose intensity of 95.9% was reported with the agent. Four patients continued to receive treatment; 65% of patients discontinued because of radiographic progression. Thirteen percent of patients discontinued treatment because of toxicities, 8% due to clinical progression, 5% due to withdrawn consent, 4% because of death, and 1% per investigator decision.

Additional data presented during the 2020 ESMO Virtual Congress demonstrated that 4% of those who received the ADC achieved disease stability while 24% experienced disease progression per IRC. Seventy-nine percent of participants also experienced a reduction in target lesions.

Notably, clinically meaningful responses were experienced irrespective of tumor histology, lines of previous treatment, responses to previous systemic treatment, and whether frontline bevacizumab/doublet chemotherapy was received. Responses were also observed irrespective of membrane TF expression level.

The median PFS reported with the ADC was 4.2 months, while the OS was 12.1 months. The PFS rate at 6 months was 30%, while the OS rate at this time point was 79%.

The ADC had a manageable safety profile. The prescribing information for the agent includes a boxed warning for ocular toxicity, as well as warning for peripheral neuropathy, hemorrhage, pneumonitis, and embryo-fetal toxicity.

The adverse effects most frequently reported with tisotumab vedotin included hemoglobin decreased (52%), fatigue (50%), lymphocytes decreased (42%), nausea (41%), peripheral neuropathy (39%), alopecia (39%), epistaxis (39%), conjunctival adverse reactions (37%), hemorrhage (32%), leukocytes decreased (30%), creatinine increased (29%), dry eye (29%), prothrombin international normalized ratio increased (26%), activated partial thromboplastin time prolonged (26%), diarrhea (25%), and rash (25%).

“[Tisotumab vedotin's] approval as a monotherapy in the United States is an important milestone for women with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy, as they are in need of a new treatment option and we look forward to making it available to them,” Jan van de Winkel, PhD, chief executive officer at Genmab, stated in a press release. “The journey toward the approval of [tisotumab vedotin] started nearly 2 decades ago with innovative research by scientists at Genmab and Seagen and reflects on our purpose of making an impact in the lives of cancer patients and their families. Today’s announcement marks Genmab’s evolution into a fully integrated biotechnology company and we would like to thank patients, caregivers, investigators and our collaborators for their participation in our clinical studies.”

1. Seagen and Genmab announce FDA accelerated approval for TIVDAK (tisotumab vedotin-tftv) in previously treated recurrent or metastatic cervical cancer. News release. Seagen Inc. and Genmab A/S. September 20, 2021. Accessed September 20, 2021. https://bit.ly/3lJOwAI

2. Coleman RL, Lorusso D, Gennigens C, et al. Tisotumab vedotin in previously treated recurrent or metastatic cervical cancer: results from the phase 2 innovaTV 204/GOG-3023/ENGOT-cx6 study. Ann Oncol. 2020;31(suppl 4):S1162-S1163. doi:10.1016/j.annonc.2020.08.2262

The FDA approved tisotumab vedotin for the treatment of adult patients with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy.

FDA OKs Tisotumab Vedotin-tftv for Patients With Recurrent or Metastatic Cervical Cancer

Interim findings from 2 expansion cohorts of the phase 1/2 innovaTV 205 trial (NCT03786081) showed that tisotumab vedotin, in combination with carboplatin as frontline therapy and pembrolizumab (Keytruda) as second- or third-line therapy, induced noteworthy responses in patients with recurrent or metastatic cervical cancer, according to findings presented at the 2021 ESMO Congress.

At a median follow-up of 7.9 months in the tisotumab vedotin/carboplatin cohort (n = 33), the objective response rate (ORR) was 55% (n = 18; 95% CI, 36%-72%), comprising 4 complete responses (12%; CRs) and 14 partial responses (42%; PRs); there were 12 cases of stable disease (36%; SD).

At a median follow-up of 13.0 months in the tisotumab vedotin/pembrolizumab cohort (n = 34), the ORR was 38% (n = 13; 95% CI, 22%-56%), comprising 2 CRs (6%) and 11 PRs (32%); there were 12 cases of SD (35%).

“Acknowledging the limited sample size, both first-line tisotumab vedotin plus carboplatin and second- and third-line tisotumab vedotin plus pembrolizumab showed encouraging and durable antitumor activity in patients with recurrent or metastatic cervical cancer,” said lead study author Ignace B. Vergote, MD, PhD, head of the Department of Obstetrics and Gynecology and Gynecologic Oncology, Catholic University of Leuven, in Belgium, in a virtual presentation of the data.

Frontline platinum and taxane chemotherapy plus bevacizumab (Avastin), if eligible, has improved survival for patients with recurrent or metastatic cervical cancer, but more effective and safer treatments are needed.

Tisotumab vedotin, an antibody-drug conjugate (ADC) that targets tissue factor, is under study for the treatment of several solid tumors, including cervical cancer.

On April 9, 2021, the FDA granted a priority review to the biologics license application (BLA) for tisotumab vedotin as a potential treatment for patients with recurrent or metastatic cervical cancer with progressive disease on, or following, chemotherapy.

The application was based on findings from the phase 2 innovaTV 204 trial (NCT03438396), which showed that 2 mg/kg of intravenous (IV) treatment with the ADC given every 3 weeks led to an ORR of 24% and a median duration of response (DOR) of 8.3 months in previously treated patients with recurrent or metastatic cervical cancer.

 Additionally, the agent had a manageable safety profile.

The recommended phase 2 dose for tisotumab vedotin in combination with pembrolizumab, carboplatin, and bevacizumab in patients with recurrent or metastatic cervical cancer enrolled in innovaTV 205 was recently reported at the 2021 International Gynecologic Cancer Society Annual Global Meeting.

The focus of the present analysis is on the carboplatin and pembrolizumab cohorts. In the carboplatin cohort, patients with no prior systemic therapy for recurrent or metastatic cervical cancer received 2 mg/kg of IV tisotumab vedotin every 3 weeks plus IV carboplatin at an area under the curve of 5 every 3 weeks. In the pembrolizumab cohort, patients with recurrent or metastatic cervical cancer with disease progression on or after 1 or 2 prior systemic treatments received 2 mg/kg of IV tisotumab vedotin every 3 weeks plus 200 mg of IV pembrolizumab every 3 weeks.

ORR per RECIST v1.1 criteria served as the primary end point; secondary end points included adverse effects (AEs) and laboratory parameters, DOR, time to response, progression-free survival (PFS), overall survival (OS), and pharmacokinetic concentrations and anti-drug antibodies associated with tisotumab vedotin.

The baseline demographics and clinical characteristics indicated that in the carboplatin and pembrolizumab cohorts, the median age was 51.0 vs 47.0 years, respectively. The majority of patients in both cohorts had an ECOG performance status of 0, squamous histology, and prior chemoradiation.

In the pembrolizumab cohort, 81.5% of patients (n = 22) were PD-L1 positive, and the majority of patients had received 1 line of prior treatment (n = 26; 74.3%) and prior bevacizumab (n = 18; 51.4%).

Additional results showed in the tisotumab vedotin/carboplatin cohort, the median PFS was 9.5 months (95% CI, 4.0-not reached [NR]), and the median OS was NR (range, 0.8+ to 14.1+). The median DOR was 8.3 months (95% CI, 4.2-NR). The median time to response was 1.4 months (range, 1.1-4.4).

The median duration of exposure was 4.9 months (range, 1-9) with tisotumab vedotin vs 4.1 months (range 1-9) with carboplatin. The median number of cycles initiated was 6.0 (range, 1-12) with tisotumab vedotin and carboplatin.

In the tisotumab vedotin/pembrolizumab cohort, the median PFS was 5.6 months (95% CI, 2.7-13.7), and the median OS was NR (range, 1.3-17.5+). The median DOR was 13.8 months (95% CI, 2.8-NR). The median time to response was 1.4 months (range, 1.3-5.8).

The median duration of exposure was 4.1 months (range, 1-16) with tisotumab vedotin vs 4.3 months (range 1-17) with pembrolizumab. The median number of cycles initiated was 6.0 (range, 1-21) with tisotumab vedotin and 6.0 months (range, 1-25) with pembrolizumab.

In terms of safety, in the tisotumab vedotin/carboplatin cohort, all patients had at least 1 treatment-emergent AE (TEAE); 97% (n = 32) of these events were related to tisotumab vedotin. Grade 3 or greater AEs occurred in 78.8% (n = 26) of patients; 57.6% (n = 19) of these events were related to tisotumab vedotin.

Serious AEs occurred in 42.4% of patients (n = 14); 15.2% (n = 5) of these events were related to tisotumab vedotin. No patients in the cohort had a fatal event.

In the tisotumab vedotin/pembrolizumab cohort, all patients had at least 1 TEAE; 97.1% (n = 34) of these events were related to tisotumab vedotin. Grade 3 or greater AEs occurred in 74.3% (n = 26) of patients; 45.7% (n = 16) of these events were related to tisotumab vedotin.

Serious AEs occurred in 51.4% of patients (n = 18); 14.3% (n = 5) of these events were related to tisotumab vedotin. One fatal event was reported in the cohort but was not determined to be related to tisotumab vedotin.

AEs that occurred in approximately half of patients in both cohorts included ocular events, bleeding events, and peripheral neuropathy.

“These data support further research to evaluate additional tisotumab vedotin combinations as interventions in recurrent or metastatic cervical cancer. The dose expansion cohort of tisotumab vedotin and pembrolizumab in first-line recurrent or metastatic cervical cancer in this study is being evaluated and will be reported at a future medical meeting,” concluded Vergote.

1. Vergote IB, Monk BJ, O’Cearbhaill RE, et al. Tisotumab vedotin (TV) + carboplatin (carbo) in first-line (1L) or + pembrolizumab (pembro) in previously treated (2L/3L) recurrent or metastatic cervical cancer (r/mCC): interim results of ENGOT-Cx8/GOG-3024/innovaTV 205 study. Presented at: 2021 ESMO Congress; September 16-21, 2021; virtual. Abstract 723MO.

2. Seagen and Genmab announce US FDA filing acceptance for priority review of tisotumab vedotin biologics license application for patients with recurrent or metastatic cervical cancer. News release. April 9, 2021. Accessed September 19, 2021. 

3. Coleman RL, Lorusso D, Gennigens C, et al. Tisotumab vedotin in previously treated recurrent or metastatic cervical cancer: results from the phase 2 innovaTV 204/GOG-3023/ENGOT-cx6 study. 

Interim findings presented at the 2021 ESMO congress suggest that tisotumab vedotin plus frontline carboplatin and second-/third-Line pembrolizumab may be a suitable treatment option for recurrent/metastatic cervical cancer. 

Gynecologic Cancers