Findings from a phase 2 trial suggest that patients with vulvar cancer and sentinel micrometastases may be able to avoid the morbidity of a lymphadenectomy by receiving inguinofemoral radiotherapy. Full study results the trial, 1 GROINSS-V-II ((NTR608/NL552) were recently published in the 

Of a total of 1535 patients registered to the trial, 21.0% (n = 322) had sentinel node metastasis. The stopping rule was activated in June 2010 because the isolated groin recurrence rate in 91 patients with sentinel node positivity went above the predefined threshold for the trial.

In 10 patients who had isolated groin recurrence, 9 had sentinel node metastases that were bigger than 2 mm and/or they had extracapsular spread. The trial protocol was amended so that those with macrometastases in the sentinel node, which was defined as bigger than 2 mm, received standard-of-care inguinofemoral lymphadenectomy (IFL). Those with sentinel node micrometastases, defined as smaller than 2 mm, continued to receive inguinofemoral radiotherapy.

Of the 160 patients with sentinel node micrometastases, 126 were given inguinofemoral radiotherapy and experienced a 2-year ipsilateral isolated groin recurrence rate of 1.6%. In the 162 patients with macrometastases in the sentinel nodes, the 2-year ipsilateral isolated groin recurrence rate was 22% in those who received radiotherapy and 6.9% in those given standard of care (

“GROINSS-V-II demonstrated that inguinofemoral radiotherapy in patients with sentinel node micrometastases results in a very low isolated groin recurrence rate, with acceptable treatment-related morbidity,” Maaike H. M. Oonk, PhD, of the Department of Obstetrics and Gynecology at The University Medical Center Groningen, The Netherlands, and colleagues, wrote. “For patients with sentinel node macrometastases, inguinofemoral radiotherapy with a total dose of 50 Gy is not a safe alternative for IFL in view of the higher risk of isolated groin recurrence.”

Over the past decade, several advances have been made in the treatment of patients with early-stage vulvar cancer. In those with unifocal tumors that are smaller than 4 cm and nonsuspicious groin nodes, a sentinel node biopsy has become standard of care rather than elective IFL. However, for those with sentinel node metastases, further treatment with IFL remains standard.

The GROINSS-V-I trial demonstrated that inguinofemoral lymphadenectomy can be safely omitted in patients who have negative sentinel nodes, leading to a significant decrease in morbidity. Patients with metastases in the sentinel node still need to undergo IFL to prevent groin recurrences, which are often fatal.

Investigators launched GROINSS-V-II to identify an equally effective, but less morbid, approach for patients with a metastatic sentinel node. To do this, they set out to determine whether inguinofemoral radiotherapy may represent a safe alternative to IFL in this population. They also wanted to examine the short- and long-term treatment-related morbidity for this strategy.

The prospective, multicenter, single-arm trial enrolled patients with early-stage vulvar cancer who were planned to undergo surgery. To be eligible for enrollment, patients needed to have unifocal microinvasive squamous cell carcinoma of the vulva that was less than 4 cm, and preoperative imaging of their groins could not reveal any suspicious nodes.

The primary end point of the research was the 24-month isolated groin recurrence rate.

Investigators utilized a radioactive tracer with performance of a lymphoscintigram and blue dye to perform sentinel node biopsies on study participants. When metastases were identified, the size and presence of extracapsular spread were noted. If the sentinel node could not be identified, an IFL was recommended. If the sentinel node was negative following ultrastaging, no further treatment was given. If tumor cells were detected, patients were regarded to have metastatic disease.

If metastatic disease in the sentinel node was identified, inguinofemoral radiotherapy was indicated. The decision of whether the treatment would be administered to 1 or both sides in those with unilateral sentinel node involvement was dependent on the participating center. Radiotherapy had to be given within 6 weeks after surgery, and it was given at a total dose of 50 Gy in 25 to 28 fractions of 1.8 Gy to 2.0 Gy, 5 fractions per week. The target dose of 50 Gy was selected because it was an effective dose for subclinical disease.

A total of 1708 patients were registered to the trial between December 2005 and October 2016. Among 1535 patients determined to meet the eligibility criteria for the trial, 79.0% (n = 1213) had a negative sentinel node and 21.0% (n = 322) had a metastatic sentinel node. Of the 322 patients with a metastatic sentinel node, 160 had micrometastases and 162 had macrometastases.

Among those with micrometastases, 78.8% (n = 126) were given inguinofemoral radiotherapy. Fourteen of these patients received radiotherapy plus chemotherapy; 9 were given cisplatin, and 5 had cisplatin and fluorouracil. Ten percent of the 126 patients underwent IFL rather than radiotherapy and 11.3% did not receive any further treatment because of either patient refusal, severe comorbidity, or older age.

Among the 160 patients, 6 isolated groin recurrences had occurred at 2 years following primary surgery; the 2-year rate was 3.8% (95% CI, 0.8%-6.8%) in this population. In the 126 patients who were given the radiotherapy, only 2 isolated ipsilateral groin recurrences were observed, in addition to 1 in a contralateral sentinel node–negative groin. Another 2 of 6 groin recurrences were reported in those who did not receive further treatment with IFL or radiotherapy. Additionally, 1 groin recurrence was observed in the contralateral sentinel node–negative groin following unilateral IFL for a metastatic node.

Among the 18 patients who were not given any additional treatment, the ipsilateral isolated groin recurrence rate proved to be higher than what was reported in those who received radiotherapy; the 2-year rates were 11.8% (95% CI, 0.0%-27.2%) and 1.6% (95% CI, 0.0%-3.9%), respectively (

Among the 162 patients who had macrometastases, 31.5% received only radiotherapy to the groins and 13.7% received radiotherapy plus chemotherapy in the form of cisplatin. Moreover, 64.8% of these patients (n = 105) had a unilateral or bilateral IFL; 56.2% of these patients also received adjuvant radiotherapy. Six patients did not receive further treatment following the removal of the sentinel nodes.

Among those with macrometastases, 19 groin recurrences were reported. The 2-year groin recurrence rates in those who received radiotherapy vs those who underwent IFL were 22.0% (95% CI, 10.5%-33.5%) and 6.9% (95% CI, 2.0%-11.8%), respectively. One recurrence was observed in a patient with 2 sentinel node macrometastases who did not receive any adjuvant treatment. No recurrences were reported in the contralateral nonirradiated groin.

Among those who received IFL, the groin recurrence rate in those who received adjuvant radiotherapy was not found to differ from those who did not receive adjuvant radiotherapy (

 = .43). In the 7 patients who received radiation plus chemotherapy, no recurrences were reported. A trend toward better disease control was observed in those who received this combination (

Of the 1213 patients who had sentinel node negativity, 31 had isolated groin recurrences. For 2 patients, metastases were noted to have been present in retrospect. In 4 patients, not all nodes visualized on the lymphoscintigram were removed. No concrete explanations were found for the other cases.

In patients with negative sentinel nodes, the estimated risk of disease-specific death at 2 years was 2.1% (95% CI, 1.3%-2.9%). In those with micrometastases, this rate was 6.5% (95% CI, 2.6%-10.4%); this rate was highest in those with macrometastases, at 25.5% (95% CI, 18.6%-32.5%; 

 < .0001). At 2 years following primary treatment, OS rates in those with negative sentinel nodes, micrometastases, and macrometastases were 95.2% (95% CI, 94.0%-96.5%), 88.3% (95% CI, 83.2%-93.4%), and 69.3% (95% CI, 62.0%-76.6%), respectively (

Of the 56 patients who experienced recurrence, 31 died from their disease during study follow-up. The estimated risk of disease-specific death at 2 years in those with macrometastases proved to be comparable in those who received IFL with or without radiotherapy and those who only received radiotherapy, at 24.2% (95% CI, 15.7%-32.6%) and 24.4% (95% CI, 12.4%-36.4%), respectively (

 = .88). Moreover, 25.5% of patients who received radiotherapy only died of vulvar cancer vs 22.9% of those who underwent IFL.

Notably, a sentinel node biopsy and subsequent radiotherapy to the groins was linked with low-grade toxicity. Cases of nausea, vomiting, mucositis, or anal and urinary incontinence were only grade 1 or 2 in severity. Diarrhea most frequently occurred at 4 to 6 weeks (grade 1, 12.3%; grade 2, 2.3%; grade 3, 0.6%) or 6 months following radiotherapy (7.9%, 0.0%, and 0.7%, respectively).

Moreover, 21.3% of patients reported grade 1 toxicity associated with the skin in the irradiated groin; in 14.8% and 1.3% of patients, respectively, this effect was grade 2 or 3 in severity. However, at 6 months, the incidence of this toxicity was found to significantly decrease. Notably, no grade 4 or 5 effects were observed.

Among patients who experienced lymphedema more than once at 6 months or 12 months following treatment, this effect was less frequent following biopsy alone, at 5.1% and 4.1%, respectively, vs when biopsy was done and followed by radiotherapy, at 16.4% and 10.7%, respectively (

 < .0001). The highest incidence of this toxicity was observed in those who underwent IFL, at 32.0% in those who also received radiotherapy and 22.9% in those who did not (

“Inguinofemoral radiotherapy for vulvar cancer patients with sentinel node micrometastases appears to be a safe alternative for IFL. The toxicity of radiotherapy is acceptable, and treatment-related morbidity is less frequent compared with IFL,” study authors concluded. “For patients with sentinel node macrometastases, radiotherapy with a total dose of 50 Gy showed more isolated groin recurrences than IFL.”

The GROINSS-V-III trial (NTR7677/NL7435) will examine radiotherapy dose escalation in combination with chemotherapy in patients with sentinel node macrometastases.

Oonk MHM, Slomovitz B, Baldwin PJW, et al. Radiotherapy versus inguinofemoral lymphadenectomy as treatment for vulvar cancer patients with micrometastases in the sentinel node: results of GROINSS-V II. 

. Published online August 25, 2021. doi:10.1200/JCO.21.00006

This article was originally published on OncLive as “Inguinofemoral Radiotherapy Represents Safe Alternative to Lymphadenectomy in Vulvar Cancer With Micrometastases”

Articles

Inguinofemoral radiotherapy may be a safe alternative for patients with vulvar cancer and sentinel node micrometastases who might otherwise face the morbidity of a lymphadenectomy.

Inguinofemoral Radiotherapy May Be Potential Alternative To Lymphadenectomy In Select Vulvar Cancer

The addition of sintilimab (Tyvt) to chemotherapy significantly improved progression-free survival (PFS) among patients with 

-mutated, nonsquamous non–small cell lung cancer (NSCLC) who disease progressed following EGFR TKI-targeted treatment. Sintilimab, a novel bevacizumab biosimilar injection (Byvasda), thus met the primary end point of the phase 3 ORIENT-31 trial (NCT03802240), leaving researchers optimistic about the future of nonsquamous NSCLC treatment. 

Data from the first interim analysis, which were reviewed by the independent data monitoring committee and were based on an assessment by the blinded independent radiographic review committee (BIRRC), showed a statistically significant and clinically meaningful PFS improvement with the combination vs pemetrexed/cisplatin alone in the intent-to-treat (ITT) population.

Moreover, sintilimab in combination with chemotherapy also demonstrated a trend toward a PFS benefit vs chemotherapy alone, although the data are not yet mature.

Additionally, the prespecified PFS futility analysis comparing sintilimab plus bevacizumab biosimilar injection and chemotherapy with sintilimab plus chemotherapy was not found to cross the futility stopping boundary. The addition of the biosimilar to sintilimab and chemotherapy has a numerical benefit.

No additional safety signals were reported with sintilimab and bevacizumab biosimilar injection.

Detailed findings from the trial will be shared at an upcoming medical conference.

“ORIENT-31 is the first prospective, double-blind, phase 3 study worldwide to demonstrate significant PFS benefit with an anti–PD-1 antibody combination therapy in this patient population,” Professor Shun Lu, Oncology Department of Shanghai Chest Hospital, and principal investigator of ORIENT-31, stated in a press release. “It has shown the clinical value of adding sintilimab plus bevacizumab biosimilar injection to platinum chemotherapy. This quadruple regimen has the potential to bring forth a new and more effective treatment option to patients with 

-mutated nonsquamous NSCLC following treatment with an EGFR TKI.”

ORIENT-31 enrolled patients with disease progression following a first- or second-generation EGFR TKI who had either confirmed 

-positive disease but progression on a third-generation EGFR TKI treatment. The trial also enrolled those who experienced progressive disease after first-line treatment with a third-generation EGFR TKI.

Study participants were randomized 1:1:1 to receive intravenous (IV) sintilimab at 200 mg every 3 weeks plus bevacizumab biosimilar injection at 15 mg/kg every 3 weeks and pemetrexed at 500 mg/m2 every 3 weeks and cisplatin at 75 mg/m2 every 3 weeks or sintilimab plus placebo 2 combined with pemetrexed/cisplatin or placebo 1 plus placebo 2 plus pemetrexed/cisplatin.2

Following a total of 4 cycles of combination therapy, participants will go on to receive maintenance treatment with sintilimab plus bevacizumab biosimilar injection and pemetrexed, sintilimab plus placebo 2 and pemetrexed, or placebo 1 plus placebo 2 and pemetrexed. Maintenance treatment will continue until radiographic disease progression, intolerable toxicity, or any other conditions that necessitate treatment discontinuation.

The trial seeks to enroll 480 participants, and the primary end point is PFS per BIRRC and based on RECIST v1.1 criteria. Key secondary end points comprise overall survival (OS), investigator-assessed PFS, objective response rate, and safety.

Previously, in May 2021, a biologics license application for the frontline use of sintilimab injection plus pemetrexed and platinum-based chemotherapy in patients with nonsquamous NSCLC was accepted by the FDA for review.3

The application was based on findings from the phase 3 ORIENT-11 trial (NCT03607539), which indicated that the combination resulted in a significant improvement in PFS compared with chemotherapy alone in this patient population.4 At a median follow-up of 8.9 months, the IRRC-assessed median PFS in the investigative and control arms was 8.9 months (95% CI, 7.1-11.3) and 5.0 months (95% CI, 4.8-6.2), respectively (HR, 0.482; 95% CI, 0.362-0.643; 

The Chinese, double-blind, randomized phase 3 ORIENT-11 study examined the safety and efficacy of sintilimab plus pemetrexed and platinum-based chemotherapy as a frontline treatment in 397 patients with nonsquamous NSCLC.

Patients had to have stage IIIB/C or IV disease and not be eligible to undergo surgery or receive local therapy. They also needed to have an ECOG performance status of 0 or 1 and have a tumor sample available for PD-L1 assessment. Patients were stratified by gender, type of platinum therapy (cisplatin vs carboplatin) and PD-L1 expression level (tumor proportion score [TPS] less than 1% vs 1% or higher).

Participants were randomized 2:1 to receive either sintilimab at 200 mg (n = 266) or placebo (n = 131) in combination with pemetrexed at 500 mg/m2 and cisplatin at 75 mg/m2 or carboplatin at area under the curve (AUC) 5, every 3 weeks for 4 cycles.

Patients in the investigative arm received sintilimab at 200 mg every 3 weeks for up to 2 years; plus pemetrexed at 500 mg/m2 every 3 weeks; those in the control arm received placebo every 3 weeks for up to 24 months plus pemetrexed at the 500 mg/m2 every-3-week dosing schedule. Thereafter, patients on the control arm were permitted to cross over to receive sintilimab at 200 mg every 3 weeks for up to 24 months.

The primary objective of the trial was PFS per IRRC. Secondary end points included OS, response rate, duration of response (DOR), time to response, and safety. Efficacy was examined in the ITT population and safety data included all patients who received at least 1 dose of study treatment.

Additional data from the trial showed that PFS benefit correlated with PD-L1 expression level. The median PFS in patients with a TPS of less than 1% was 7.3 months (95% CI, 6.2–not reached [NR]) vs 5.1 months (95% CI, 4.6-7.8) with sintilimab and chemotherapy alone, respectively (HR, 0.664; 95% CI, 0.406-1.086). In those with a TPS of 1% to 49%, the median PFS was 7.1 months (95% CI, 6.2-9.2) and 4.8 months (95% CI, 2.5-8.0), respectively (HR, 0.503; 95% CI, 6.2-9.2). In those with the highest PD-L1 TPS of 50% or greater, the median PFS had not yet been reached (95% CI, 9.2–NR) with sintilimab vs 5.0 months (95% CI, 4.3-6.8) with chemotherapy alone (HR, 0.310; 95% CI, 0.197-0.489).

The addition of sintilimab was also found to result in an approximate 40% reduction in the risk of death vs chemotherapy alone, which was determined to be nominally significant (HR, 0.609; 95% CI, 0.400-0.926; 

= .01921). The 6-month OS rates in the investigative and control arms were 89.6% and 80.4%, respectively.

Moreover, the sintilimab combination induced an objective response rate (ORR) of 51.9% vs 29.8% with chemotherapy alone. The disease control rates achieved in the investigative and control arms were 86.8% and 75.6%, respectively. Time to response was shorter in the sintilimab arm vs the chemotherapy-alone arm, at 1.5 months and 2.6 months, respectively.

The most common toxicities included anemia, reduced neutrophil count, reduced white blood cell count, reduced platelet count, increased aspartate aminotransferase, increased alanine aminotransferase, nausea, reduced appetite, asthenia, vomiting, constipation, and pyrexia.

Innovent announces ORIENT-31, a phase 3 study of sintilimab in patients with EGFR-mutated nonsquamous non-small cell lung cancer with prior EGFR-TKI treatment, has met primary endpoint. News release. Innovent Biologics, Inc. October 17, 2021. Accessed October 18, 2021. 

Sintilimab +/- IBI305 plus chemotherapy (pemetrexed + cisplatin) for EGFRm + locally advanced or metastasis non-squamous NSCLC patients after EGFR-TKI treatment failure. ClinicalTrials.gov. Updated April 9, 2020. Accessed October 18, 2021. 

https://clinicaltrials.gov/ct2/show/NCT03802240

US FDA accepts regulatory submission for sintilimab in combination with pemetrexed and platinum chemotherapy for the first-line treatment of people with nonsquamous non-small cell lung cancer. News release. Innovent Biologics, Inc. May 18, 2021. Accessed October 18, 2021. 

Zhang Li, Yang Y, Wang Z, et al. ORIENT-11: sintilimab + pemetrexed + platinum as first-line therapy for locally advanced or metastatic non-squamous NSCLC. 

. 2020;15(10). doi:10.1016/j.jtho.2020.08.002

This article was originally published on OncLive as “Novel Sintilimab Combo Significantly Improves PFS in EGFR-Mutated Nonsquamous NSCLC”

Sintilimab, a bevacizumab biosimilar injection, met the primary end point of the phase 3 ORIENT-31 trial by significantly increasing progression-free survival in patients with EGFR-mutated, nonsquamous, non–small cell lung cancer. 

Sintilimab Plus Chemotherapy Induces Superior Survival in EGFR-Mutated Nonsquamous NSCLC

A real-world analysis presented at the 2021 Kidney Cancer Research Summit (KCRS) showed that axitinib (Inlyta) plus pembrolizumab (Keytruda) didnot induce clinically meaningful survival rates in patients with metastatic renal cell carcinoma (RCC) compared with ipilimumab (Yervoy) plus nivolumab (Opdivo). 1

The median progression-free survival in the intent-to-treat (ITT) population was 9.0 months with axitinib plus pembrolizumab vs 6.9 months with ipilimumab plus nivolumab (

 = .20). In the patients with a favorable International Metastatic RCC Database Consortium (IMDC) risk, the real-world PFS was not reached with axitinib/pembrolizumab vs 6.9 months with ipilimumab plus nivolumab; however, this was not determined to be clinically significant, and the sample size was small. In those with intermediate/poor risk, the PFS was 9.0 months with axitinib plus pembrolizumab vs 6.0 months with ipilimumab plus nivolumab.

The median overall survival (OS) in the ITT population was not yet reached with axitinib/pembrolizumab vs 23.7 months with ipilimumab/nivolumab (

 = .10). In those with favorable risk, the median OS had not yet been reached with either regimen. In those with intermediate/poor risk, the median OS was not reached with axitinib plus pembrolizumab vs 22.0 months (95% CI, 18.2-26.4) with ipilimumab plus nivolumab.

“When we look at landmark 18-month survival, you can appreciate that as the IMDC risk goes from favorable to intermediate/poor, survival decreases,” Kevin Zarrabi, lead study author and hematology/oncology fellow at Fox Chase Cancer Center, said in a presentation on the data. “However, there is absolutely no discernible difference between the [patients treated with] axitinib/pembrolizumab vs ipilimumab/nivolumab. Survival seems almost identical.”

Data from the phase 3 CheckMate-214 trial (NCT02231749) showed that in a sample size of 1096 patients, ipilimumab plus nivolumab improved OS and objective response rates (ORR) vs sunitinib (Sutent) in previously untreated patients with intermediate- and poor-risk advanced RCC.2

The median PFS with the doublet was 11.6 months (95% CI, 8.7-15.5) vs 8.4 months (95% CI, 7.0-10.8) with the monotherapy. The landmark 12-month OS rates in the investigative and control arms in IMDC all-risk patients were 83% (95% CI, 80%-86%) and 77% (95% CI, 74%-81%), respectively. The ORRs in IMDC all-risk patients were 39% (95% CI, 35%-43%) and 32% (95% CI, 28%-36%), respectively. Data from the trial resulted in the April 2018 FDA approval of the combination for use in patients with intermediate- or poor-risk, previously untreated advanced RCC.3

The combination of axitinib plus pembrolizumab was found to prolong OS and PFS in a sample size of 861 patients with advanced RCC, as well as elicit a higher ORR compared with sunitinib, according to data from the phase 3 KEYNOTE-426 trial (NCT02853331).4

Results showed that the median PFS with the doublet vs the monotherapy was 15.1 months (95% CI, 12.6-17.7) and 11.1 months (95% CI, 8.7-12.5), respectively. The median PFS in the intermediate- and poor-risk patients in the investigative and control arms was 12.6 months and 8.2 months, respectively. The landmark 12-month OS rates in the all-risk population were 89.9% and 78.3%, respectively; the ORRs were 59.3% (95% CI, 54.5%-63.9%) and 35.7% (95% CI, 31.1%-40.4%), respectively. Findings from this trial supported the April 2019 FDA approval for axitinib/pembrolizumab for use in the frontline treatment of patients with advanced RCC.5

“Although these were remarkable advances in terms of treatment options for [our patients with] clear cell RCC, we don’t have head-to-head prospective data to help guide us in treatment choice,” Zarrabi explained. “When looking at the IMDC criteria and survival we do know that in the intermediate- and poor-risk patient population, there’s no real clear signal advantage in terms of either treatment option.”

Common practice, with respect to practitioner comfort with combination therapies as well as patient preference and goals, is to tailor treatment, according to Zarrabi. However, a gap in knowledge exists due to lack of data; as such, it is difficult to discern whether an advantage exists with either regimen in this population.

To fill this gap, Zarrabi and colleagues partnered with Flatiron Health to look at survival data on 9940 treatment-naïve patients with metastatic RCC stored in the electronic health record database, which houses healthcare information for over 3 million patients treated at 280 community and academic sites.

Investigators looked at information from 2018, when ipilimumab plus nivolumab emerged in the treatment landscape, through March 2021, a total of 1045 patients with clear cell RCC were identified for inclusion in the analysis. “This is a fairly large sample size compared with what is already in the literature,” Zarrabi said.

Of the 1045 patients included in the final cohort, 698 had received treatment with ipilimumab plus nivolumab and 347 received axitinib plus pembrolizumab.

The patient demographic and clinical characteristics were well balanced, with no real preference for one combination regimen over another, according to Zarrabi.

The median age of patients who received axitinib/pembrolizumab was 68.0 years (range, 21-85) vs 66.0 years (range, 29-84) with ipilimumab/nivolumab. Most patients were male (70.6% and 75.6%, respectively), White (70.0% and 63.6%), intermediate/poor risk (80.5% and 84.9%), had stage IV disease at diagnosis (56.2% and 60.06%), and received treatment in community settings (92.8% and 90.3%).

“In 2018, when the ipilimumab/nivolumab data were released, more patients were receiving that combination,” Zarrabi noted. “However, over the ensuing 3.5 years, there seems to be provider preference to move toward axitinib/pembrolizumab.”

Longer-term survival outcomes have recently been reported for both CheckMate-2146 and KEYNOTE-426 and survival benefit was found to be sustained.7 In CheckMate-214, the median PFS with ipilimumab/nivolumab in patients with intermediate/poor risk RCC was 11.6 months and the median OS was 47.0 months. In the real-world dataset, the median PFS and OS was 6.9 months and 22.0 months, respectively. The 18-month landmark survival rate was 77% in the ITT population vs 58.8% in the real-world dataset.

In KEYNOTE-426, the median PFS with axitinib/pembrolizumab was 15.7 months and the median OS was 45.7 months. In the real-world dataset, the median PFS was 9.0 months and the median OS had not yet been reached. The 18-month landmark survival rate in the ITT population was 81.0%; this rate was 58.2% in the real-world dataset.

“Not surprisingly, we see a significantly lower survival [in terms of both] PFS and OS in our real-world population compared with the trial population,” Zarrabi noted.

In the absence of prospective studies, retrospective analyses such as the report shared during the 2021 KCRS are utilized to guide decision making when it comes to frontline treatment choice for this patient population, according to Zarrabi.

“Longer follow-up time will be necessary to discern any clinically significant difference in survival,” Zarrabi concluded. “Future studies may include data on newly approved frontline combination therapies, including lenvatinib [Lenvima]/pembrolizumab and cabozantinib [Cabometyx]/nivolumab.”

Zarrabi K, Handorf EA, Miron B, et al. Real-world outcomes of front-line axitinib plus pembrolizumab versus ipilimumab plus nivolumab for metastatic clear cell renal cell carcinoma: landmark 18-month survival analysis. Presented at: 2021 Kidney Cancer Research Summit; October 7-8, 2021; Philadelphia, PA.

Motzer RJ, Tannir NM, McDermott DF, et al. Nivolumab plus ipilimumab versus sunitinib in advanced renal cell carcinoma. 

. 2018;378(14):1277-1290. doi:10.1056/NEJMoa1712126

FDA approves nivolumab plus ipilimumab combination for intermediate or poor-risk advanced renal cell carcinoma. News release. FDA. April 16, 2018. Accessed October 12, 2021. https://bit.ly/3lyohOx

Rini BI, Plimack ER, Stus V, et al. Pembrolizumab plus axitinib versus sunitinib for advanced renal-cell carcinoma. 

. 2019;380(12):1116-1127. doi:10.1056/NEJMoa1816714

FDA approves pembrolizumab plus axitinib for advanced renal cell carcinoma. News release. FDA. April 19, 2019. Accessed October 12, 2021. https://bit.ly/3BDk3uH

Motzer RJ, Escudier B, McDermott DF, et al. Survival outcomes and independent response assessment with nivolumab plus ipilimumab versus sunitinib in patients with advanced renal cell carcinoma: 42-month follow-up of a randomized phase 3 clinical trial. 

. 2020;8(2):e000891. Doi:10.1136/jitc-2020-000891

Powles T, Plimack ER, Soulières D, et al. Pembrolizumab plus axitinib versus sunitinib monotherapy as first-line treatment of advanced renal cell carcinoma (KEYNOTE-426): extended follow-up from a randomised, open-label, phase 3 trial. 

. 2020;21(12):1563-1573. doi:10.1016/S1470-2045(20)30436-8

This article was originally published on OncLive as “Analysis Examines Real-World Survival Outcomes With Frontline Combos in Metastatic RCC”

A real-world survival analysis showed that patients with metastatic RCC treated with axitinib plus pembrolizumab did not experience significantly improved survival outcomes compared with patients treated with ipilimumab plus nivolumab. 

Axitinib/Pembrolizumab Combination Improves Survival in Metastatic RCC, But Only Marginally 

The biopharmaceutical company Athenex Inc. has shared that they will be shifting their focus away from oral paclitaxel encequidar for patients with metastatic breast cancer to focus on other issues examining oral paclitaxel.

 This announcement came about following a Type A meeting with the FDA to discuss deficiencies highlighted in a complete response letter (CRL) issued in response to their new drug application for the regimen.

In the CRL, which was issued in March 2021, the regulatory agency stated that although the review cycle for the application was complete, the application was not ready for approval due to safety concerns, as an increase in neutropenia-associated effects had been observed in those who received the treatment vs those who were administered intravenous (IV) paclitaxel.

The FDA also shared concerns regarding the data from the primary end point of blinded independent central review (BICR)–assessed objective response rate (ORR) at week 19 in the single pivotal phase 3 trial evaluating the regimen. It was stated that the BICR reconciliation and reread process could have introduced unmeasured bias and influence on the review.

At the time, the agency had recommended that the company initiate a “new, adequate, well-conducted” trial in patients with metastatic breast cancer that would be representative of the population of patients cared for in the United States. They also specified that more risk-mitigation approaches, such as dose optimization and/or the exclusion of those considered to be at increased risk of toxicity, be utilized to improve safety.

The purpose of the Type A meeting was to further discuss a proposed design for such a trial, and to consider the potential US regulatory path forward for oral paclitaxel in this disease.

“We had an informative meeting with the FDA, which was an important step to assessing the US regulatory pathway for oral paclitaxel in metastatic breast cancer,” Johnson Lau, MD, chief executive officer of Athenex, Inc., stated in a press release. “After careful consideration of the FDA feedback, we have determined to redeploy our resources to focus on other ongoing studies of oral paclitaxel and our promising CAR natural killer T-cell and T-cell receptor therapies to maximize value for all stakeholders. We also remain committed to serving patients utilizing products manufactured by our specialty pharmaceutical business (APS and APD).”

The NDA for oral paclitaxel plus encequidar was supported by data from 

, which had showed that this approach significantly improved ORR vs IV paclitaxel in patients with metastatic breast cancer, meeting the primary end point of the research.

 The oral approach elicited an ORR of 36% vs 24% with the IV approach in this population.

Responders who experienced a duration of response to treatment that continued for 150 days or longer was found to be 2.5 times longer than what had been reported with IV paclitaxel.

The trial enrolled a total of 402 patients who were then randomized in a 2:1 fashion to receive oral paclitaxel plus encequidar (n = 265) or IV paclitaxel (n = 137). The primary end point of the trial was ORR per RECIST v1.1 criteria at 2 consecutive time points. Baseline patient characteristics were noted to be balanced across the treatment arms.

At a July 25, 2019 data cutoff, a trend toward improved progression-free survival was observed in the investigative arm vs the control arm (

= .077), as well as a trend toward improved overall survival (

Patients who received the oral approach reported lower rates of neuropathy compared with those who received the IV approach. Specifically, 17% of those on the investigative arm experienced neuropathy vs 57% of those on the control arm. Lower rates of alopecia, arthralgia, and myalgia were also observed by those who received oral paclitaxel plus encequidar vs IV paclitaxel.

The treatment arms experienced similar rates of neutropenia; however, more patients who received the oral approach experienced grade 4 neutropenia and infection. A higher rate of gastrointestinal toxicities was observed in the investigational arm vs the control arm.

Athenex provides update from FDA type A meeting regarding oral paclitaxel + encequidar in metastatic breast cancer. News release. Athenex, Inc. October 11, 2021. Accessed October 12, 2021. 

Athenex receives FDA complete response letter for oral paclitaxel plus encequidar for the treatment of metastatic breast cancer. News release. Athenex, Inc. March 1, 2021. Accessed October 12, 2021. 

Athenex announces oral paclitaxel and encequidar had a significantly higher response rate over IV paclitaxel in a phase III pivotal study in metastatic breast cancer. News release. Athenex, Inc. August 7, 2019. Accessed October 12, 2021. 

After a Type A meeting with the FDA regarding oral paclitaxel/encequidar in metastatic breast cancer, Athenex, Inc. has announced that they will be deploying their resources to other avenues of research.

FDA Type A Meeting Steers Oral Paclitaxel/Encequidar Research in New Direction

The FDA has approved brexucabtagene autoleucel (Tecartus; formerly KTE-X19) as a treatment for adult patients with relapsed/refractory B-cell precursor acute lymphoblastic leukemia (B-ALL).

The regulatory decision was based on findings from the phase 1/2 ZUMA-3 study (NCT02614066), which showed that at a median follow-up of 16.4 months (range, 10.3-22.1), a single infusion of the CAR T-cell therapy elicited a high and durable response rate in heavily pretreated patients with relapsed/refractory B-ALL, the majority of whom had a high disease burden.

Specifically, data from the phase 2 portion of the trial presented during the 2021 ASCO Annual Meeting showed that brexucabtagene autoleucel elicited a complete response/complete response with incomplete blood count recovery (CR/CRi) rate of 70.9%, which included a CR rate of 56.4%.

The international, multicenter, phase 1/2 trial enrolled patients with relapsed/refractory B-ALL and bone marrow blasts that were greater than 5% who were at least 18 years of age. Notably, patients were not able to have previously received blinatumomab (Blincyto).

Earlier results from the phase 1 portion of the research showed that brexucabtagene autoleucel had a manageable toxicity profile with an overall CR/CRi rate of 83%. The recommended phase 2 dose of the CAR T-cell product was determined to be 1 x 106 CAR T cells/kg.

Seventy-one adult patients were enrolled to the phase 2 portion of the trial and they received conditioning chemotherapy comprised of fludarabine 25 mg/m2 on days -4, -3, and -2, as well as cyclophosphamide at 900 mg/m2 on day -2. A single infusion of the CAR T-cell therapy was administered on day 0 at a dose of 1 x 106 anti-CD19 CAR T cells/kg.

The primary end point of the trial was CR/CRi rate by central assessment, and key secondary end points included minimal residual disease (MRD) negativity rate, duration of response (DOR), relapse-free survival (RFS), overall survival, safety, and CAR T-cell levels in the blood and cytokine levels in serum.

Of the 71 patients enrolled to the trial, 14 patients did not receive treatment because of toxicities (n = 7), eligibility criteria were not met (n = 3), product was not available (n = 1), patient consent was withdrawn (n = 1), or for other reasons not specified (n = 2). A total of 57 patients were given conditioning chemotherapy; 2 of these patients did not receive treatment after this, which left 55 patients who received the CAR T-cell therapy.

Among the study participants, the median age was 40 years (range, 19-84), and the majority were male (60%) with an ECOG performance status of 1 (71%). Additionally, 27% of patients had Philadelphia chromosome positivity and all had central nervous system disease at baseline. Patients received a median of 2 prior therapies (range, 1-8) and 47% of patients had undergone 3 or more prior lines of treatment.

The majority of patients has relapsed on, or were refractory to, 2 or more prior systemic lines of treatment (78%); 45% of patients had received prior treatment with blinatumomab, 22% previously received inotuzumab ozogamicin (Besponsa), and 42% had undergone prior autologous stem cell transplant (ASCT). Moreover, the median rate of bone marrow blasts at screening was 65% (range, 5%-100%), and the median rate at preconditioning after bridging chemotherapy was 59% (range, 0%-98%).

Moreover, the median time to initial CR/CRi was 1.1 months (range, 0.85-2.99). In responders, the MRD negativity rate with the CAR T-cell therapy was 97%, with a sample unavailable for 1 patient. Eighteen percent of patients received ASCT at a median of 98 days (range, 60-207) after having received the CAR T product.

The median DOR was 12.8 months, with or without censoring patients at subsequent ASCT. As of data cutoff, 31% of the patients who achieved a CR or CRi experienced ongoing remissions without receiving subsequent ASCT. Additionally, the median RFS was 11.6 months and 14.2 months for those who achieved a CR/CRi.

Regarding safety, the most common grade 3 or higher adverse effects (AEs) included anemia (49%) and pyrexia (36%). Ten cases of grade 5 AEs were reported, 4 of which were ALL; 2 were treatment-emergent from the CAR T-cell product and included brain herniation and septic shock; 3 occurred after initiation of another cancer treatment and included fungal pneumonia, sepsis, and respiratory failure; and 1 was pneumonia unrelated to treatment with brexucabtagene autoleucel.

No grade 5 cytokine release syndrome (CRS) or other neurological AEs were reported. However, 24% of patients experienced grade 3 or higher CRS and 25% reported other grade 3 or higher neurological events. To treat these AEs, patients were given tocilizumab (Actemra; 80%), steroids (75%), and vasopressors (40%).

U.S. FDA Approves Kite’s Tecartus® as the First and Only Car T for Adults With Relapsed or Refractory B-cell Acute Lymphoblastic Leukemia. Kite. News release. Published October 1, 2021. Accessed October 1, 2021. https://bwnews.pr/3iq0Chg.

Shah B, Ghobadi A, Oluwole O, et al. Phase 2 results of the ZUMA-3 study evaluating KTE-X19, an anti-CD19 chimeric antigen receptor T-cell therapy, in adult patients with relapsed/refractory B-cell acute lymphoblastic leukemia. 

. 2021;39(15):7002-7002. doi:10.1200/JCO.2021.39.15_suppl.7002

Shah BD, Bishop MR, Oluwole OO, et al. End of phase I results of ZUMA-3, a phase 1/2 study of KTE-X19, anti-CD19 chimeric antigen receptor (CAR) T cell therapy, in adult patients (pts) with relapsed/refractory (R/R) acute lymphoblastic leukemia (ALL). 

. 2019;37(suppl; abstr 70060). doi:10.1200/JCO.2019.37.15_suppl.7006

This article was originally published on OncLive as “FDA Approves Brexucabtagene Autoleucel for Relapsed/Refractory B-ALL”

Brexucabtagene autoleucel is now an FDA approved treatment options for adult patients with relapsed/refractory B-cell precursor acute lymphoblastic leukemia.

FDA Green Lights Brexucabtagene Autoleucel for Relapsed/Refractory B-ALL Treatment

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

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

Kristi Rosa

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