Ashling Wahner

Imbruvica plus R-MPV led to high response rates and was tolerable for patients with newly diagnosed primary central nervous system lymphoma.

Rituxan (rituximab) plus methotrexate, procarbazine and vincristine (R-MPV) plus Imbruvica (ibrutinib; R-MPV/i) induction therapy showed a high complete response rate (CR) rate and was shown to be tolerable in patients with newly diagnosed primary central nervous system (CNS) lymphoma (PCNSL), meeting the primary and key secondary end points of a phase 2 trial.

Data was presented at the 2025 SNO Annual Meeting.

At a median follow-up of 32.1 months, the overall response rate (ORR) was 100%, including a CR rate of 90% (27 patients) and an unconfirmed CR rate of 7% (2 patients), translating to an overall CR rate of 97% (29 patients). Additionally, the partial response rate was 3% (1 patient). No patients had refractory disease, and the median time to best response was 110 days.

The median progression-free survival (PFS) and overall survival (OS) were not reached. In total, four patients progressed with a median time to progression of 15.2 months. The two-year PFS rate was 84.2%, and the three-year PFS rate was 78.6%.

“The CR rate and the two-year PFS [rate] were much better than what you would expect, regardless of our consolidation measurement,” lead study author Dr. Christian Grommes, said in the presentation. “The question [you] might ask is: Is the addition of Imbruvica potentially modulating consolidation to a less aggressive approach?” Grommes is a neuro-oncologist at Memorial Sloan Kettering Cancer Center in New York, New York.

Complete response rate (CR): percentage of patients whose cancer completely disappears with treatment.

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

Progression-free survival (PFS): time patients live without their cancer growing or spreading.

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

ECOG performance score: scale that describes a patient’s ability to carry out daily activities, ranging from fully active to fully disabled.

What is the rationale for investigating R-MPV plus Imbruvica in newly diagnosed PCNSL?

PCNSL is an aggressive form of non-Hodgkin lymphoma that develops in the CNS. Approximately 90% of cases of PCNSL present as diffuse large B-cell lymphoma. Recurrent B-cell receptor signaling axis mutations in genes like MYD88 and CD79B are common in this disease and can be targeted, according to Grommes.

Methotrexate (MTX)/R-MPV is a common induction regimen used to treat patients with newly diagnosed PCNSL. Grommes explained that previously, a prospective trial conducted at Memorial Sloan Kettering Cancer Center showed that induction therapy with R-MPV generated a 66% CR rate, a median PFS of 3.3 years, and a two-year PFS rate of 78% in this patient population. Additionally, the multicenter phase 2 NRG1114 trial demonstrated a CR rate of 76% and a two-year PFS rate of 54% with R-MPV plus cytarabine in this patient population.

Furthermore, a phase 2 trial showed a 74% ORR with Imbruvica monotherapy in patients with recurrent PCNSL.Collectively, these data supported the rationale for evaluating Imbruvica plus R-MPV in patients with newly diagnosed PCNSL.

“The idea that we had was to move…agents that are successful in the recurrent, refractory setting in reducing tumor size into the up-front [setting],” Grommes explained.

What was the safety profile of R-MPV/i in patients with PCNSL?

The most common any-grade side effects were decreased platelet counts (30 patients), lymphopenia (29 patients), anemia (28 patients), increased alanine aminotransferase (ALT) levels (28 patients), and increased aspartate aminotransferase (AST) levels (28 patients). The most common grade 3 (severe) side effects were lymphopenia (19 patients), anemia (16 patients), decreased white blood cell (WBC) counts (13 patients), decreased neutrophil counts (9 patients), increased ALT levels (9 patients), decreased platelet counts (4 patients), increased AST levels (3 patients), and increased creatine levels (1 patient).

No grade 5 (death) side effects were reported. Grade 4 (life-threatening) toxicities included neutropenia (4 patients), lymphopenia (3 patients), thrombocytopenia (3 patients), and decreased WBC counts (3 patients). Although Grommes noted that cardiotoxicity is a concern with the use of Imbruvica, in this trial, only two patients developed atrial fibrillation, and only one patient developed deep venous thrombosis. Investigators reported no major hemorrhage or Aspergillus/Pneumocystis infections.

“The combination of R-MPV plus Imbruvica is an excellent combination with excellent probability, especially no fungal infections, no major cardiac problems, and no hemorrhagic [side effects],” Grommes concluded.

What was the design of the phase 2 trial evaluating R-MPV/i in patients with newly diagnosed PCNSL?

This trial enrolled patients at least 18 years of age with newly diagnosed PCNSL who had an ECOG performance score of 2 or lower and normal end-organ function. Patients who had received 1 to 2 prior doses of methotrexate were allowed to enroll.

Patients were treated over four 28-day cycles with:

Rituxan at 500 milligrams per square meter (mg/m

Imbruvica at 560 mg on days 5 to 14 and 19 to 28 of each cycle

Consolidation treatment was determined by the investigators.

The primary end point was overall CR rate at end of induction. Secondary end points included safety and tolerability, PFS and OS.

“Imbruvica in combination with Rituxan, methotrexate, vincristine, and procarbazine for newly diagnosed primary CNS lymphoma” by Dr. Schaff, et al., presented at the 2025 SNO Annual Meeting.

“MTX-based chemotherapy combined with low-dose whole-brain radiotherapy improves progression-free survival for patients with newly diagnosed CNS lymphoma” by NRG Oncology, news release.

“A phase 2 study assessing long-term response to Imbruvica monotherapy in recurrent or refractory CNS lymphoma” by Dr. Grommes, et al., 

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Rituximab, methotrexate, procarbazine, and vincristine (R-MPV) combined with ibrutinib (Imbruvica) demonstrated high efficacy and tolerability in newly diagnosed primary CNS lymphoma (PCNSL) patients, achieving a 97% complete response rate in a phase 2 trial. The trial reported a 100% overall response rate, with no refractory cases and a median time to best response of 110 days. The two-year progression-free survival rate was 84.2%. The regimen's safety profile was manageable, with common side effects including lymphopenia and anemia, and no grade 5 toxicities observed.

Imbruvica Plus Drug Combo Shows Strong Responses in Newly Diagnosed PCNSL

Intraventricular B7-H3 CAR T-cell therapy was well tolerated up to 1 x 10⁷ cells per infusion and showed early signs of activity in recurrent glioblastoma.

At the 2025 SNO Annual Meeting, investigators presented interim results from the first-in-human phase 1 LCCC 2059 study showing that intraventricular infusion of B7-H3–directed CAR T-cell therapy was well tolerated in patients with recurrent glioblastoma at doses up to 1 x 10⁷ CAR T cells per infusion, meeting the primary safety objective.

Among nine evaluable patients who were enrolled across three dose levels (2 x 10

, 3 patients) of CAR T-cells per infusion, no dose-limiting toxicities (DLTs) were reported. A total of two patients developed mild cytokine release syndrome (CRS); no patients experienced moderate or severe CRS. No patients had immune effector cell–associated neurotoxicity syndrome of any grade, and no grade 3 (severe) or higher adverse effects were deemed related to CAR T-cell infusion. Notably, two patients had moderate headache. No patients needed to be admitted to the intensive care unit or receive toxicity management treatment with Kineret (anakinra) or Actemra (tocilizumab).

Among the nine evaluable patients, the median age was 49 years, and 78% of patients were male. All patients completed the scheduled three weekly infusions. Best radiographic responses included partial response (PR; 22%; 2 patients) and stable disease (22%; 2 patients), translating to a disease control rate of 44%. One of the patients with PR achieved this response by 24 weeks and remained in response for eight months after infusion. The other patient with PR achieved this response by the end of the DLT period. The median overall survival was 10.2 months.

“This is an ongoing clinical trial, and we are enrolling on dose level 5, [which is 6 x 10

 CAR T cells], at this time,” lead study author Dr. Yasmeen Rauf, stated in the presentation.

Rauf is an assistant professor of neurology and neurosurgery at the University of North Caroline (UNC) School of Medicine, as well as the interim division chief of Neuro-Oncology at the UNC Lineberger Comprehensive Cancer Center in Chapel Hill.

What is currently known about the story of B7-H3 targeted therapy in brain cancer?

Currently patients with glioblastoma have a median survival of approximately 14.6 months and 5-year survival rates below 5%. B7-H3 is widely expressed in glioblastoma and has minimal expression in normal brain tissue, making it an attractive therapeutic target.

B7-H3–directed CAR T-cell therapy is under investigation in other brain cancer populations as well. For instance, in May 2025, the FDA granted regenerative medicine advanced therapy designation to the CAR T-cell therapy BCB-276, which targets B7-H3, for the treatment of patients with diffuse intrinsic pontine glioma.

What was the design of the phase 1 trial investigating B7-H3–directed CAR T-cell therapy in patients with glioblastoma?

This dose-escalation study used a 3 plus 3 design. It enrolled patients at least 18 years of age with histologically confirmed recurrent glioblastoma, a Karnofsky performance score of greater than 60, and measurable disease of at least 1 centimeter. Patients were not permitted to have prior Avastin (bevacizumab) treatment.

Patients received three weekly intraventricular infusions across six planned dose levels ranging from 1 x 10

 CAR T cells, followed by a two-week DLT period. Autologous CAR T cells were manufactured through RNA electroporation. Radiographic responses were measured every eight weeks per Immunotherapy Response Assessment in Neuro-Oncology criteria. Notably, patients who progressed on this study treatment received additional treatment.

“It takes us about three to four weeks, sometimes five weeks, for manufacturing of the CAR T cells,” Rauf noted.

Safety and tolerability served as the primary end point of the trial. Secondary end points were feasibility and preliminary efficacy.

What did a case study show about the efficacy of B7-H3–directed CAR T-cell therapy in a specific patient?

Rauf presented findings from a case of a 46-year-old patient with IDH wild-type glioblastoma who received six weeks of concurrent radiation and Temodar (temozolomide), followed by five cycles of adjuvant temozolomide. After presenting with progression, this patient received two cycles of Gleostine (lomustine). Upon second progression, the patient was enrolled onto LCCC 2059 and received three weekly infusions of CAR T cells at dose level 3 x 10

 CAR T cells. Following the DLT period, this patient’s brain MRI appeared stable, and a subsequent MRI displayed a durable PR.

“Safety and tolerability of intraventricular infusion of B7-H3.CAR-T cells in recurrent glioblastoma,” by Dr. Rauf Y, Higgins D, Buchannan B, et al. Presented at: 2025 SNO Annual Meeting; November 19-23, 2025; Honolulu, Hawaii. Abstract CTIM-32.

“FDA grants regenerative medicine advanced therapy designation for BrainChild Bio’s B7-H3 CAR T-cell therapy for incurable pediatric brain tumors.” News release. BrainChild Bio. May 15, 2025. Accessed May 19, 2025. https://brainchildbio.com/wp-content/uploads/2025/05/BrainChild-Bio-RMAT-PR_FINAL.pdf

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Interim results from a phase 1 study of B7-H3–directed CAR T-cell therapy in recurrent glioblastoma patients demonstrated promising safety and tolerability. Nine patients received intraventricular infusions across three dose levels, with no dose-limiting toxicities or severe adverse effects reported. The study achieved a disease control rate of 44%, with partial responses in two patients. The median overall survival was 10.2 months. The trial continues to enroll patients at higher dose levels, with safety and preliminary efficacy as primary and secondary endpoints, respectively.

B7-H3 CAR T-Cell Therapy Shows Acceptable Safety in Recurrent Glioblastoma

Early data from the SJ901 study show Gomekli generates responses with manageable side effects in children and young adults with low grade glioma.

Gomekli (mirdametinib) showed clinical activity with acceptable safety in children, adolescents and young adults with recurrent or progressive low-grade glioma (pLGG) with biopsy-proven MAPK pathway activation who had not been treated with a prior MEK inhibitor, according to findings from the phase 1/2 SJ901 trial, presented at the 2025 SNO Annual Meeting.

At a data cutoff date of September 23, 2025, the overall response rate (ORR) per Response Assessment in Pediatric Low-Grade Glioma radiological response criteria was 87%, including minor response or better (87%), partial response (PR) or better (55%), major response or better (26%), and complete response (6%). The median time to minor response or better was 6 months, and the median time to PR or better was 10.7 months.

Overall, the efficacy of Gomekli was seen in 36% of patients who received the agent at 2 milligram per square meter (mg/m

 and 46% of those who received it at 3 mg/m

. Therefore, the recommended phase 2 dose (RP2D) was identified to be 3 mg/m

 twice daily given orally and for continuous dosing based on the finding that only one patient out of 12 who received the agent at this dose level had a dose-limiting toxicity (DLT; grade 3 thrombocytopenia).

“We are very excited about the preliminary efficacy,” lead study author and presenter Dr. Anna Vinitsky, said in an interview with 

® during the meeting. Vinitsky is an associate member of St. Jude Faculty at St. Jude Children’s Research Hospital in Memphis, Tennessee.

Treatment-related adverse effects (TRAEs) that led to dose reductions (34%) included grade 3 (severe) weight gain (8 patients), grade 4 (life-threatening) elevated creatine phosphokinase (CPK) levels (2 patients), grade 3 elevated alanine aminotransferase (ALT) levels (1 patient), and decreased platelet counts (1 patient). TRAEs that led to treatment discontinuations (6%) included intolerable grade 2 rash (1 patient) and grade 4 elevated CPK levels (1 patient). AEs of special interest included asymptomatic grade 2 decreased left ventricular ejection fraction to less than 50% (3 patients); each had spontaneous resolution. Notably, investigators did not report retinal toxicities of any grade.

“We’re quite thrilled that patients are tolerating the drug well,” Dr. Giles W. Robinson, added in the interview. “They have some of the more customary AEs we see with MEK inhibitors, which are rashes, paronychia, or ingrown toenails. But these are relatively minor [AEs] that the patients learn to manage, or parents learn to manage for the patients.”

Robinson is a member of St. Jude Faculty, director of the Division of Neuro-Oncology, co-leader of Cancer Center Neurobiology and Brain Tumor Program in Memphis.

What was the rationale for the SJ901 trial of Gomekli in pLGG?

Although MEK inhibitors have shown promise as treatment for pediatric low-grade glioma, they often have limited penetrance to the blood-brain barrier and are often not available in oral formulations, according to the study authors. Gomekli, however, is an oral, selective, small-molecule MEK inhibitor that can penetrate the blood-brain barrier and can be administered in a dispersible tablet formulation that is more amenable for the needs of young children and patients for whom swallowing pills is a challenge. Gomekli was FDA approved in February 2025 for the treatment of adult and pediatric patients at least two years of age with neurofibromatosis type 1 (NF1) who have symptomatic plexiform neurofibromas (PNs) that are not amenable to complete resection.

Based on Gomekli’s mechanism of action, oral formulation, and efficacy in patients with NF1 PNs, investigators launched the SJ901 trial to investigate the agent in patients with pLGG.

This multi-arm trial enrolled patients with pLGG at least 2 years of age but younger than 25 years of age. The phase 1 portion of the trial enrolled those with recurrent or progressive pLGG with biopsy-proven MAPK pathway activation (except in BRAF V600) who had no prior exposure to a MEK inhibitor. MAPK pathway activation was defied as BRAF fusions or rearrangements; FGFR1/2/3 aberrations; NF1, NF2, PTPN11, SOS1, RAF1 and RAS mutations; and MYB or MYBL1 fusions or rearrangements, all identified by immunohistochemistry, fluorescence in situ hybridization, and/or DNA/RNA sequencing.

Patients received Gomekli at 1 of 3 escalating dose levels (2 mg/m

) twice daily on a continuous schedule over 24 months. An expansion cohort was designed to find the highest tolerated dose level, which would become the RP2D, in 12 patients. Once the RP2D was identified, an additional 12 patients were treated at this level to determine the efficacy of the agent across 24 total patients. The RP2D was defined as the dose that was associated with 3 or fewer DLTs in 12 patients; DLTs were defined as any toxicities that limited the administration of a given Gomekli dose within the first cycle of therapy.

The primary objectives of SJ901 were to explore the safety, tolerability, and preliminary efficacy of continuous Gomekli administration as well as to identify the RP2D of the agent.

What additional efficacy findings were reported from the SJ901 trial at SNO 2025?

Between June 2021 and September 2025, 35 total patients were enrolled to the phase 1, phase 1 expansion, and phase 2 cohort 2 portions of the trial. In the overall population, the median age at diagnosis was 8.3 years, and most patients were male (54%) and White (77%). Primary diagnoses included pilocytic astrocytoma (83%), diffuse glioma (6%), diffuse leptomeningeal glioneuronal tumor (3%), glioneuronal tumor (3%), and LGG not otherwise specified (6%). MAPK gene abnormalities were seen in BRAF (65%), FGFR1 (17%), MYB (3%), NF1 (9%), and RAF1 (6%).

At a median follow-up of 23.9 months, 83% of patients had completed or remained on therapy. In total, 17% of patients had discontinued therapy due to progression (4 patients; FGFR aberration, 2 patients; MYB fusion or rearrangement, 1 patient; BRAF fusion or rearrangement, 1 patient) and toxicity (2 patients; rash and increased CPK levels). Additionally, 9 patients progressed either on therapy (5 patients) or after completing therapy (4 patients).

“Patients [had] more than 50% reductions in the size of their tumor, which some of these tumors are quite large and are causing a lot of debilitating deficits in our patient population,” Robinson added. “When we see that [reduction], we also see that these patients are incredibly thriving.”

What additional safety findings have been reported with Gomekli in pLGG?

In total, the most common TRAEs included increased CPK levels (35 patients), increased aspartate aminotransferase levels (32 patients), dry skin (19 patients), acneiform rash (18 patients), anemia (16 patients), weight gain (16 patients), paronychia (15 patients), hair color changes (14 patients), increased ALT levels (12 patients), increased alkaline phosphatase levels (12 patients), decreased neutrophil counts (11 patients), maculopapular rash (11 patients), eczema (8 patients), hypoalbuminemia (8 patients), nausea (8 patients), diarrhea (7 patients), hypomagnesemia (7 patients), proteinuria (7 patients), decreased platelet counts (6 patients), skin and subcutaneous tissue disorders or other TRAEs (6 patients), fatigue (5 patients), and hypernatremia (5 patients).

What are the next steps for evaluating Gomekli in patients with pLGG?

Continued results will be shared from the trial as the data from this patient cohort mature, according to the study authors. Cohorts 1 and 3 of the phase 2 portion of the trial are enrolling newly diagnosed patients and those who have been previously treated with MEK inhibition, respectively.

“We would love to see this drug become a standard therapy in LGG,” Robinson concluded. “That is the direction we’re heading [in]. There needs to be more studies in looking at how does this drug fare with other MEK inhibitors, and how does it fare in comparison with what we consider standard of care? But to be honest, [from] treating patients and seeing patients in the clinic thriving on this therapy, it feels like they’re doing much better than what we’ve seen with standard chemotherapies. We are encouraged that this will become one of the therapies of the future for LGG.”

“Efficacy and tolerability of mirdametinib (PD-0325901) in children, adolescents, and young adults with recurrent/progressive low-grade glioma: update from the SJ901 (NCT04923126) phase 1/2 clinical trial,” by Dr. Vinitsky A, Bag AK, Chiang J, et al. Presented at: 2025 SNO Annual Meeting; November 19-23, 2025; Honolulu, Hawaii. Abstract CTP-08.

“FDA approves mirdametinib for adult and pediatric patients with neurofibromatosis type 1 who have symptomatic plexiform neurofibromas not amenable to complete resection.” FDA. February 11, 2025. Accessed November 21, 2025. 

https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-Gomekli-adult-and-pediatric-patients-neurofibromatosis-type-1-who-have-symptomatic

Gomekli (mirdametinib) demonstrated promising clinical activity and acceptable safety in pediatric patients with recurrent or progressive low-grade glioma (pLGG) with MAPK pathway activation, as shown in the SJ901 trial. The trial identified a recommended phase 2 dose of 3 mg/m2 twice daily, with an overall response rate of 87%. Common treatment-related adverse effects included weight gain, elevated CPK levels, and rashes. The trial aims to establish Gomekli as a standard therapy for pLGG, with ongoing studies comparing its efficacy to other MEK inhibitors and standard treatments.

Gomekli Shows Early Activity in Pediatric Low Grade 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.

Ashling Wahner

Imbruvica Plus Drug Combo Shows Strong Responses in Newly Diagnosed PCNSL

B7-H3 CAR T-Cell Therapy Shows Acceptable Safety in Recurrent Glioblastoma

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