Kyle Doherty

Eflornithine plus Gleostine was associated with superior overall survival and progression-free survival in grade 3 IDH-mutated astrocytoma.

Among patients with recurrent grade 3 IDH-mutated astrocytoma, 

he addition of eflornithine to Gleostine (lomustine) was associated with clinically meaningful overall survival (OS) and progression-free survival (PFS) benefits when compared with treatment via Gleostine alone, study results have shown.

Updated data from the phase 3 STELLAR study were presented during the 2025 Society of Neuro-Oncology Annual Meeting.

In the updated analysis, investigators reclassified patients from the original intention-to-treat (ITT) population (343 patients) using updated molecular classification to identify a subset of patients (57%) who had grade 3/4, IDH-mutated astrocytoma.

Progression-Free Survival (PFS): This measures how long a patient lives without their cancer getting worse (progressing).

Overall Survival (OS): The length of time from the start of diagnosis or treatment until a patient dies.

Karnofsky Performance Status (KPS): This is a score (from 0 to 100) that doctors use to measure a patient's general well-being and their ability to perform daily activities.

Myelosuppression: This is a side effect where a treatment, like chemotherapy or radiation, slows down or stops the production of new blood cells in the bone marrow (the soft tissue inside your bones).

Patients with grade 3 or 4 disease who received the combination (116 patients) achieved a median OS of 28.5 months compared with 22.3 months among those who received Gleostine monotherapy (119 patients). The median PFS values were 12.3 months and 7.3 months, respectively. Additionally, findings from a blinded independent central MRI review of PFS among patients with grade 3 disease revealed that the PFS benefit with eflornithine was consistent with the investigator-assessed PFS benefit.

“This updated classification based on [World Health Organization] 2021 [criteria] of the STELLAR population confirms the benefit of eflornithine in grade 3, IDH-mutant, CDK-intact population,” Dr. Howard Colman explained during the presentation. “The blinded independent review of the MRI results confirms the PFS benefit observed by investigators and the high correlation between the effect of PFS and OS in this subgroup. This is the first demonstration of a clinically significant OS and PFS benefit in a randomized study in this population.”

Colman is a Jon M. Huntsman Presidential Professor in the Department of Neurosurgery, a member of the multidisciplinary Brain Tumor Research Team and the leader of the Center for Neurologic Cancers at Huntsman Cancer Institute (HCI) at the University of Utah. He is also an HCI investigator and a member of the Experimental Therapeutics program.

STELLAR was an open-label study that enrolled patients a surgical or biopsy-proven diagnosis of WHO grade 3 anaplastic astrocytoma. Patients were also required to have experienced their first instance of disease progression or recurrence at least six months after the completion of external beam radiation therapy (ERBT). Prior treatment with ERBT and Temodar (temozolomide) plus chemotherapy prior to the first instance of disease progression or recurrence was required, as was a Karnofsky Performance Status (KPS) of at least 70 and adequate organ function.

“The STELLAR trial started in 2016 under the prior WHO diagnostic criteria, [and] this created several difficulties, but [an] extensive effort was made to gather historical archival tissue to reclassify the population based on 2021 WHO criteria,” Colman explained.

Patients were randomly assigned to receive eflornithine plus Gleostine (arm A) or Gleostine monotherapy (arm B). Patients in arm A received eflornithine at 2.8 g/m

 on a two-weeks-on, one-week-off schedule for up to 24 months in combination with Gleostine at 90 mg/m

 once on day 15 and once every six weeks during the eflornithine off weeks for up to six cycles or 12 months, whichever came first. Patients in arm B received Gleostine at 100 mg/m

 once every six weeks for up to six cycles or 12 months, whichever came first.

At baseline, the median age in the ITT population (343 patients) was 43 years. Most patients were 45 years old or younger (56%), male (60.9%), underwent one or two surgical resections (86%), and had a KPS of at least 90 (68.0%). The median time from the last dose of radiation therapy to random assignment was 26.6 months.

Previously reported data for the ITT population showed that patients treated with the combination (172 patients) achieved a median OS of 23.4 months versus 20.3 months for those given Gleostine alone (171 patients). The median PFS was 8.9 months versus 7.2 months, respectively.

What was the safety profile of the combination?

In terms of safety, patients in the combination arm experienced grade 3 (severe) or higher treatment-emergent side effects related to eflornithine or Gleostine at respective rates of 50.9% and 45.6%. Grade 3 or higher treatment-emergent side effects of relevance were reported at a rate of 63.9% and included myelosuppression (39.6%), hearing loss (23.7%) and diarrhea (9.5%). Serious treatment-emergent side effects related to eflornithine or Gleostine were reported at rates of 7.7% and 3.6%, respectively.

In the monotherapy arm, grade 3 or higher treatment-emergent side effects related to Gleostine occurred in 33.3% of patients. Grade 3 or higher TEAEs of relevance (30%) included myelosuppression (28.7%), seizure (1.3%) and nausea (0.7%). Serious treatment-emergent side effects related to study treatment were also reported (2.7%).

“[The] toxicities were consistent with prior eflornithine; gastrointestinal [side effects] and decreased hearing were the notable toxicities,” Colman said.

“Updated results of phase 3 STELLAR trial: eflornithine improves overall survival and blinded independent central review determined progression free survival in patients with recurrent WHO 2021 grade 3 IDH-mutant astrocytoma” by Dr. Howard Colman et al. Presented at: 2025 SNO Annual Meeting; November 19-23, 2025; Honolulu, HI. Abstract CTNI-58.

“Study to evaluate eflornithine + lomustine vs lomustine in recurrent anaplastic astrocytoma (AA) patients (STELLAR);” https://clinicaltrials.gov/study/NCT02796261

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Articles

The addition of eflornithine to Gleostine in patients with recurrent grade 3 IDH-mutated astrocytoma demonstrated significant improvements in overall survival (OS) and progression-free survival (PFS) compared to Gleostine alone. The phase 3 STELLAR study reclassified patients using updated molecular criteria, confirming the benefits of eflornithine in this subgroup. The combination therapy showed a median OS of 28.5 months versus 22.3 months for monotherapy. Safety profiles indicated higher rates of severe side effects with the combination, including myelosuppression and hearing loss, consistent with known eflornithine toxicities.

Eflornithine Plus Gleostine Improves Progression, Survival In Some With Astrocytoma

Voranigo plus Temodar was safe in glioma with IDH1/2 mutations.

Among patents with IDH1- or IDH2-mutant glioma, the treatment combination of Voranigo (vorasidenib) plus Temodar (temozolomide) did not lead to any serious side effects or dose-limiting toxicities (DLTs), clinical trial results have shown.

Data from the phase 1b IDHEAL-4U trial were presented at the 2025 Society for Neuro-Oncology Annual Meeting.

Findings demonstrated that, with a median treatment duration 5.5 months, all patients (seven patients) experienced any-grade treatment-emergent side effects; 28.6% (two patients) had grade 3 (severe) or higher treatment-emergent side effects, which included decreased neutrophil count (14.3%) and decreased platelet count (28.6%). No patients discontinued treatment due to treatment-emergent side effects, and all patients completed the DLT evaluation portion of the study. As of the Sept. 8, 2025, data cutoff, 85.7% (six patients) remained on treatment with both study drugs.

Increased alanine aminotransferase (ALT) levels: 

ALT is an enzyme found mostly in the liver. When ALT levels are higher than normal on a blood test, it can be a sign that the liver is irritated or damaged. 


The Karnofsky performance status is a score doctors use to describe how well a person with cancer is able to carry out daily activities. The scale goes from 0 to 100. A higher number means the person is more active and able to care for themselves; a lower number means they need more help. 

Treatment-emergent side effects led to dose reductions in 42.9% of patients; notably, 14.3% required dose reductions of only Voranigo, 28.6% needed dose reductions of only Temodar, and no patients required dose reductions of both agents. Dose reductions of Voranigo stemmed from increased alanine aminotransferase (ALT) levels (14.3%), and reductions of Temodar were due to decreased platelet count (28.6%) and decreased neutrophil count (14.3%).

Treatment-emergent side effects required study drug interruption in 57.1% of patients, including 28.6% who needed dose interruptions of both treatments, which was due to increased ALT levels (28.6%). Only Voranigo was interrupted in 14.3% of patients, and only Temodar was interrupted in 57.1% of patients. Treatment-emergent side effects leading to dose interruptions of only Voranigo included increased ALT levels (14.3%), and these included neutropenia (42.9%) and decreased platelet count (42.9%) for Temodar only.

“Based on data from the May 6, 2025, data cutoff, the safety review committee declared [Voranigo at] 40 mg as the recommended combination dose [RCD] to be given in combination with standard-of-care [Temodar],” lead study author Dr. Macarena de la Fuente and colleagues wrote in a poster presentation of the data.

de la Fuente is an associate professor of neuro-oncology, chief of the Neuro-Oncology Division, clinical service leader for Neuro-Oncology Service Line - Sylvester Comprehensive Cancer Center, chair of the Neuro-Oncology Site Disease Group, director of the Neuro-Oncology Fellowship Program, and oncology clinical service leader for Neuro-Oncology at the Miller School of Medicine of University of Miami in Florida.

Why are Voranigo and Temodar being evaluated as a combination strategy in 

Although Voranigo is approved by the FDA for the treatment of adult and pediatric patients 12 years of age and older with grade 2 astrocytoma or oligodendroglioma with a susceptible IDH1 or IDH2 mutation, as detected by an FDA-approved test, following surgery including biopsy, sub-total resection, or gross total resection, treatment with IDH inhibitor monotherapy is unlikely to lead to disease control in patients with higher-grade, more aggressive gliomas.

As such, de la Fuente and colleagues hypothesized that adding Voranigo to Temodar could, “exploit the molecular vulnerabilities of higher-grade [IDH1/2-mutant] gliomas while controlling more rapidly proliferative tumor cells.”

IDHEAL-4U is a multicenter phase 1b/2 trial designed to evaluate the combination, with phase 1b focusing on safety, and the ongoing phase 2 portion looking at preliminary efficacy, safety, and tolerability for the RCD in patients with grade 4 astrocytoma harboring IDH1/2 mutations.

In phase 1b, investigators enrolled patients at least 12 years of age with grade 2 to 4 gliomas with IDH1/2 mutations who were eligible for Temodar in the adjuvant setting after radiotherapy or at first disease recurrence.

Voranigo was first evaluated at 40 mg once per day in combination with Temodar at 150 mg/m

 in cycles 2 to 12. Voranigo was continued until disease progression. After safety review committee input and analysis of DLT rate and BOIN design, investigators could dose de-escalate to evaluate Voranigo to 20 mg per day, or declare the RCD.

What were the patient characteristics in phase 1b?

The seven enrolled patients had a median age of 36 years, and 57.1% were female. Karnofsky performance status at baseline included 100 (14.3%), 90 (57.1%), 80 (14.3%) and 70 (14.3%). Patient tumor types included frontline grade 3 astrocytoma (42.9%), frontline grade 4 astrocytoma (14.3%), recurrent grade 4 astrocytoma (14.3%), frontline grade 3 oligodendroglioma (14.3%) and recurrent grade 4 oligodendroglioma (14.3%).

All patients had received prior radiation therapy. Three patients (42.9%) received prior systemic therapy, which was exclusively Temodar.

“Phase 1b safety results of vorasidenib in combination with temozolomide in patients with mutant IDH1 or IDH2 glioma” by Dr. Macarena de la Fuente et al., presented at: 2025 SNO Annual Meeting; November 19-23, 2025; Honolulu, HI. Abstract CTNI-34.

The combination of Voranigo and Temodar in IDH1/2-mutant glioma patients showed no serious side effects or dose-limiting toxicities in a phase 1b trial. All patients experienced treatment-emergent side effects, with 28.6% experiencing severe side effects. Dose reductions were necessary for 42.9% of patients, primarily due to increased ALT levels and decreased blood counts. The recommended combination dose for Voranigo was established at 40 mg. The trial aims to exploit molecular vulnerabilities in higher-grade gliomas, with ongoing evaluation of efficacy, safety, and tolerability in phase 2.

Voranigo Plus Temodar Found to Be Safe in Patients With IDH1/2+ Glioma

The addition of postsurgical Verzenio to endocrine therapy provided a benefit in HR–positive, HER2-negative breast cancer.

Among patients with hormone receptor (HR)-positive, HER2-negative, high-risk early breast cancer, postsurgical, or adjuvant, Verzenio (abemaciclib) plus endocrine therapy was associated with a 15.8% reduction in the risk of death when compared with endocrine therapy alone, clinical trial results have shown.

Findings from the primary overall survival (OS) analysis of the phase 3 monarchE trial were presented at the 2025 ESMO Congress.

At a median follow-up of 76 months (6.3 years) and a data cutoff date of July 15, 2025, all patients had stopped receiving Verzenio for at least four years. There were 301 OS events in the Verzenio arm versus 360 in the endocrine therapy–alone arm. The OS rates at 60, 72 and 84 months were 91.2%, 89.2% and 86.8% in the Verzenio arm versus 90.2%, 87.9% and 85.% in the control arm.

Overall Survival (OS): This is the length of time from diagnosis or the start of treatment that patients are still alive. It helps doctors understand how well a treatment may be working.

Invasive Disease–Free Survival (IDFS): This refers to the time after treatment during which a person has no signs of cancer coming back or spreading. It specifically focuses on more serious (invasive) cancer returning.

Distant Relapse–Free Survival (DRFS): This means how long a patient stays free from the cancer returning in other parts of the body (far from where it started), after finishing treatment.

Pharmacokinetics (PK): This is the study of how a medicine moves through the body—how it's absorbed, used, and cleared out. It helps doctors decide on the right dose and timing for treatment.

“[Verzenio] represents the first CDK4/6 inhibitor to achieve a statistically significant improvement in OS for these high-risk, node-positive patients,” Dr. Stephen Johnston stated in the presentation.

Johnston is head of the Breast Unit, a professor of breast cancer medicine, and a consultant medical oncologist at The Royal Marsden NHS Foundation Trust and The Institute of Cancer Research in London, United Kingdom.

What Was the Impetus for Conducting the monarchE Trial?

“Improving OS and cure rates is the goal of adjuvant therapy in early breast cancer, but it's difficult to prove OS, and we often approve treatments on benefits in reducing risk of recurrence,” Johnston explained.

He summarized key findings from the past several years of investigating endocrine therapy in patients with hormone receptor–positive early breast cancer, including reductions in the risk of death conferred by the use of tamoxifen versus no treatment, the use of an aromatase inhibitor (AI) versus tamoxifen, and the use of extended AI treatment versus 5 years of endocrine therapy. He noted that unlike in prior trials, previously reported data from monarchE indicated that an OS benefit could emerge from the addition of Verzenio to endocrine therapy versus endocrine therapy alone. 

What Was the Design of the monarchE Trial?

monarchE enrolled patients with hormone receptor–positive, HER2-negative, mode-positive, high-risk early breast cancer. Cohort 1 included patients with high-risk disease based on clinical and pathological factors, including at least four positive axillary lymph nodes or one to three positive axillary lymph nodes and grade 3 disease and/or a tumor size of at least 5 cm. Cohort 2 included patients with high-risk disease based on Ki-67 score, defined as one to three positive axillary lymph nodes plus a Ki-67 score of at least 20%, as well as grade 3 or lower disease and a tumor size of less than 5 cm.

Patients in cohort 1 (5,637 patients) were randomly assigned to receive Verzenio at 150 mg twice daily plus endocrine therapy or endocrine therapy alone for the on-treatment study period of two years. During the follow-up period, patients received endocrine therapy for three to eight years as clinically indicated. Patients were stratified by prior chemotherapy, menopausal status and region.

The primary end point was invasive disease–free survival (IDFS). Secondary end points included IDFS in the high Ki-67 populations, distant relapse–free survival (DRFS), OS, safety, pharmacokinetics, and patient-reported outcomes.

What Data Have Been Previously Reported From monarchE?

The initial readout of the monarchE trial showed that patients who received two years of adjuvant Verzenio plus endocrine therapy had significant improvements in IDFS compared with those who received endocrine therapy alone. Furthermore, at the five-year landmark analysis of the trial, at a median follow-up of 54 months, the IDFS and DRFS benefits with Verzenio were sustained, and an OS trend favoring the Verzenio arm had emerged, although it had not yet reached statistical significance.

What Additional Data Were Seen in the Primary OS Analysis of monarchE?

In the primary OS analysis, the OS benefit with the addition of Verzenio was consistent across prespecified patient subgroups. However, Johnston emphasized that the point estimates for the individual subgroups should be interpreted with caution because the trial was not powered or controlled to evaluate treatment effects in individual subgroups.

There were approximately 30% fewer patients living with metastatic disease in the Verzenio arm versus the control arm. In the Verzenio arm, 2.8% of patients (n = 80) had died from causes unrelated to breast cancer, 7.9% of patients (n = 221) had died due to breast cancer, and 6.4% of patients (n = 180) were alive with metastatic disease. In the control arm, these rates were 2.3% (n = 64), 10.5% (n = 296), and 9.4% (n = 266), respectively.

The addition of Verzenio to endocrine therapy reduced the risk of IDFS events by 26.6% compared with endocrine therapy alone. There were 547 and 722 IDFS events in these respective arms.

During the follow-up period, the respective IDFS rates in the Verzenio and control arms were as follows:

A consistent IDFS benefit was observed across all prespecified subgroups.

Johnston noted that most IDFS events observed in the trial were distant metastatic disease, and that the addition of Verzenio reduced the number of patients with metastases at common sites. In the Verzenio arm (2,808 patients), 18% of patients in the intent-to-treat (ITT) population had a first recurrence, consisting of distant recurrence (13.6%), local/regional recurrence (2.5%), second primary neoplasm (1.7%) and contralateral breast cancer (0.5%). The sites of initial distant recurrence in this arm included bone (5.9%), liver (3.5%), lung (2.5%), brain/central nervous system (CNS; 1.1%), lymph node (1.0%) and pleura (0.3%).

In the control arm (2,829 patients), 24.5% of patients in the ITT population had a first recurrence, consisting of distant recurrence (18.5%), local/regional recurrence (3.9%), second primary neoplasm (1.8%) and contralateral breast cancer (0.8%). The sites of initial distant recurrence in this arm included bone (9.4%), liver (4.7%), lung (2.7%), brain/CNS (1.1%), lymph node (1.6%) and pleura (1%).

Overall, investigators observed low rates of second primary neoplasms across both arms.

A sustained DRFS benefit with the addition of Verzenio was also observed, reducing the risk of DRFS events by 25.4% compared with endocrine therapy alone. There were 476 DRFS events in the Verzenio arm versus 621 DRFS events in the control arm.

During the follow-up period, the respective DRFS rates in the Verzenio and control arms were as follows:

The investigators also reported a consistent DRFS benefit with Verzenio across prespecified subgroups.

Among patients in the Verzenio arm with distant recurrence who entered the post-two-year treatment follow-up period (407 patients), 78.9% received any first systemic therapy in the first-line metastatic setting, 32.7% received chemotherapy, 46.7% received endocrine therapy, 33.2% received targeted therapy (CDK4/6 inhibitor, 30.0%; PI3K/AKT/mTOR inhibitor, 3.2%) and 5.2% received other therapy. These respective rates in the control arm (565 patients) were 83.4%, 23.7%, 58.4%, 484.8% (CDK4/6 inhibitor, 47.3%; PI3K/AKT/mTOR inhibitor, 0.7%) and 4.8%.

Differences in CDK4/6 inhibitor and chemotherapy use between the arms were predominantly seen among patients with early recurrences and were less pronounced among those with later recurrences. Among patients with early recurrences, the rates of chemotherapy and CDK4/6 inhibitor use were 43.5% and 15.2%, respectively, in the Verzenio arm (191 patients) versus 26.8% and 44.7%, respectively, in the control arm (313 patients). Among patients with late recurrences, the usage rates of these respective classes of therapy were 23.1% and 43.1% in the Verzenio arm (216 patients) versus 19.8% and 50.4% in the control arm (252 patients).

“This makes clinical sense,” Johnston reported. “Patients relapsing on their adjuvant CDK4/6 inhibitor may be more likely to be offered chemotherapy. Those who have not had it in the adjuvant setting may be offered it for their metastatic disease. Remember, this was a global trial. Investigators could treat the patients as they saw fit. Globally, not all therapies in metastatic disease are equally available around the world, so we do not believe that this analysis confounds the OS impact we've seen. If there were more CDK4/6 inhibitors [used] in the endocrine therapy–alone arm, that might diminish the OS benefit, not enhance it.”

What Were the Long-Term Safety Findings From monarchE?

Safety results from long-term follow-up were consistent with those from prior analyses, because all treated patients had completed treatment at least four years prior. Investigators observed no relevant differences in side effect–related causes of death between the two arms.

Among safety-evaluable patients in the Verzenio arm (2,791 patients), during therapy, 15 deaths occurred; the most common causes of death were infections and infestations (COVID-19, three patients) and cardiac disorders (five patients). Following treatment discontinuation in this arm, 197 patients had at least one serious side effect during late-term follow-up, regardless of causality. There were 44 deaths attributed to side effects, including infections and infestations (13 patients; COVID-19, six patients), second primary neoplasm (13 patients) and cardiac disorders (six patients).

Among safety-evaluable patients in the control arm (2,800 patients), during therapy, 11 deaths occurred; the most common causes of death were infections and infestations (five patients; COVID-19, one patient) and second primary neoplasm (one patient). Following treatment discontinuation in this arm, 213 patients had at least one serious side effect during late-term follow-up, regardless of causality. There were 30 deaths attributed to side effects, including infections and infestations (five patients; COVID-19, two patients), second primary neoplasm (seven patients) and cardiac disorders (nine patients).

“The seven-year analysis has continued to show a sustained benefit in IDFS and DRFS, and there are no new safety signals,” Johnston concluded.

“Overall survival with abemaciclib in early breast cancer” by Dr. Stephen Johnston, et al. 

“Abemaciclib combined with endocrine therapy for the adjuvant treatment of HR+, HER2-, node-positive, high-risk, early breast cancer (monarchE)” by Dr. Stephen Johnston, et al.

“Adjuvant abemaciclib plus endocrine therapy for hormone receptor-positive, human epidermal growth factor receptor 2-negative, high-risk early breast cancer: results from a preplanned monarchE overall survival interim analysis, including 5-year efficacy outcomes” by Dr. Priya Rastogi et al., 

The phase 3 monarchE trial demonstrated that adding Verzenio (abemaciclib) to endocrine therapy significantly reduced the risk of death by 15.8% in patients with hormone receptor-positive, HER2-negative, high-risk early breast cancer. The trial, with a median follow-up of 76 months, showed improved overall survival (OS) and invasive disease-free survival (IDFS) rates in the Verzenio arm compared to endocrine therapy alone. The study highlighted Verzenio as the first CDK4/6 inhibitor to achieve a statistically significant OS improvement in this patient population, with consistent benefits across subgroups.

Verzenio Plus Endocrine Therapy Benefits Survival for Some With Breast Cancer

Camrelizumab plus famitinib extended progression-free survival to 11.1 months versus 7.5 months with chemotherapy in recurrent or metastatic cervical cancer.

Camrelizumab in combination with famitinib produced superior progression-free survival (PFS) outcomes versus platinum-based chemotherapy for the frontline treatment of patients with recurrent or metastatic cervical cancer, according to data from a phase 3 trial presented during the 

At the June 10, 2025, data cutoff, at a median follow-up of 19.3 months, the median progression-free survival (PFS) per blinded independent central review (BICR) was 11.1 months in the combination arm (220 patients) compared with 7.5 months in the chemotherapy arm (223 patients). The median PFS values per investigator assessment were 11.3 months and 7.7 months, respectively.

“The chemotherapy-free regimen of camrelizumab/famitinib significantly prolonged PFS and overall survival [OS] compared with platinum-based chemotherapy with or without bevacizumab [Avastin] as first-line treatment in recurrent/metastatic cervical cancer,” Dr. Xiaohua Wu, chief physician, professor and supervisor of oncology, as well as the chairman and chief expert in the Department of Gynecologic Oncology at Fudan University Shanghai Cancer Center in China, said during the presentation. “This regimen met the dual primary end points at interim analysis.”

How was the phase 3 trial designed and what were the baseline characteristics?

The open-label, controlled, multicenter study enrolled patients with histopathologically confirmed, recurrent or metastatic squamous cell carcinoma of the cervix. Patients were required to not be amenable to curative therapy, surgery, radiotherapy or chemoradiotherapy and could not have received prior systemic therapy for recurrent or metastatic disease. Other key inclusion criteria included having at least one measurable tumor lesion according to RECIST 1.1 criteria and an ECOG performance status of 0 or 1.

Progression-free survival (PFS): time during and after treatment that a patient lives without the cancer growing or spreading.

Overall survival (OS): time from treatment start until death from any cause.

Overall response rate (ORR): percentage of patients whose cancer shrinks or disappears after treatment.

Disease control rate (DCR): percentage of patients whose cancer shrinks, disappears, or remains stable after treatment.

Duration of response (DOR): length of time a treatment keeps cancer under control after it first responds.

Time to response (TTR): time from treatment start until the cancer first shows a response.

ECOG performance status: scale used by doctors to measure how well a patient can carry out daily activities, ranging from 0 (fully active) to 5 (dead).

Patients were randomly assigned one-to-one to receive intravenous (IV) camrelizumab at 200 milligrams (mg) every three weeks for up to 35 cycles plus oral famitinib at 20 milligrams daily, or platinum-based chemotherapy every three weeks for up to 6 cycles with or without IV bevacizumab at 15 milligrams per square meter every three weeks. Stratification was performed by PD-L1 combined positive score (CPS; greater than or equal to 1 versus less than 1) and prior use of platinum (yes versus no).

The dual primary end points were BICR-assessed PFS per RECIST 1.1 criteria and overall survival (OS). Secondary end points included investigator-assessed PFS, overall response rate (ORR), disease control rate (DCR), duration of response (DOR), time to response (TTR) and safety.

At baseline, the median ages in the combination and chemotherapy arms were 55 years and 54 years, respectively. Most patients in these respective arms had a PD-L1 CPS of at least 1 (93.2% versus 92.8%), had metastatic disease (97.7% versus 97.3%), had received prior platinum-containing therapy (70.9% versus 70%) and had received prior therapy (95.5% versus 96%). At diagnosis, patients had stage 1 (15.9% versus 13.9%), 2 (32.7% versus 35.4%), 3 (38.2% versus 37.2%), 4A (0.5% versus 1.8%), 4B (8.2% versus 8.1%) or unknown (4.5% versus 3.6%) disease. Prior therapies included surgery (48.2% versus 44.8%), radiotherapy (85.5% versus 88.3%) and systemic anticancer treatment (86.8% versus 85.7%); 30.9% of patients in the chemotherapy arm received bevacizumab during the study.

What were the additional efficacy data and safety profile of the combination?

The median OS in the combination arm was 34.4 months compared with 23.4 months in the chemotherapy arm. Findings from a subgroup analysis revealed that the PFS benefit in favor of the combination arm was reported in all prespecified subgroups except for the subgroup of patients with a PD-L1 CPS of less than 1. The OS benefit with the combination was reported in all prespecified subgroups.

The BICR-assessed confirmed ORR in the combination arm was 52.3% versus 46.6% in the chemotherapy arm, including respective complete response rates of 10.9% and 8.5%. The confirmed DCRs were 81.8% and 77.6%, respectively. The median DORs were 17.9 months and 8.3 months, respectively, and the respective median TTRs were 2.2 months and 2.1 months.

In terms of safety, any-grade treatment-emergent side effects occurred in 99.5% of patients in the combination arm and 99.1% of patients in the chemotherapy arm. Patients in both arms experienced grade 3 to 5 treatment-related side effects (87.3% versus 67.1%), serious treatment-related side effects (34.5% versus 19.2%), as well as side effects leading to treatment discontinuation (13.6% versus 6.6%), dose interruption (83.6% versus 37.6%) and dose reduction (65% versus 12.2%). Patients in the combination arm experienced any-grade immune-related (38.2%) and grade 3 to 5 immune-related (7.3%) side effects; no such events were reported in the chemotherapy arm.

The most common any-grade side effects in the combination arm included decreased white blood cell count (79.5%), decreased neutrophil count (75%) and anemia (70%). These were also the most common any-grade side effects in the chemotherapy arm, occurring at respective rates of 73.7%, 70% and 75.6%.

“The safety profile was manageable. These study findings show that camrelizumab plus famitinib could serve as a novel first-line treatment option for this patient population,” Wu said in his conclusion.

“Phase 3 study of camrelizumab plus famitinib versus platinum-based chemotherapy as first-line therapy for recurrent or metastatic cervical cancer” by Dr. Xiaohua Wu, et al., 

“Camrelizumab combined with famitinib malate for treatment of recurrent/metastatic cervical cancer” by Dr. Xiaohua Wu, et al., 

For more news on cancer updates, research and education,

Camrelizumab combined with famitinib demonstrated superior progression-free survival (PFS) and overall survival (OS) compared to platinum-based chemotherapy in patients with recurrent or metastatic cervical cancer. The phase 3 trial showed a median PFS of 11.1 months for the combination versus 7.5 months for chemotherapy. The combination also achieved a median OS of 34.4 months compared to 23.4 months for chemotherapy. Despite a higher incidence of treatment-related side effects, the safety profile was deemed manageable, suggesting the combination as a potential first-line treatment option.

Kyle Doherty

Eflornithine Plus Gleostine Improves Progression, Survival In Some With Astrocytoma

Voranigo Plus Temodar Found to Be Safe in Patients With IDH1/2+ Glioma

Verzenio Plus Endocrine Therapy Benefits Survival for Some With Breast Cancer

Camrelizumab Combo Extends Survival in Metastatic Cervical Cancer

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