BACKGROUND:Dual anti-human epidermal growth factor receptor 2 (HER2) therapy plus chemotherapy followed by maintenance treatment with HER2-targeted and endocrine therapies is standard first-line treatment for hormone-receptor-positive, HER2-positive metastatic breast cancer. On the basis of preclinical and clinical data, the addition of palbociclib (a selective inhibitor of cyclin-dependent kinases 4 and 6) may overcome resistance to both endocrine and HER2-directed therapies. METHODS:In this phase 3, open-label, randomized trial, we enrolled patients with hormone-receptor-positive, HER2-positive metastatic breast cancer who did not have disease progression after four to eight cycles of chemotherapy plus HER2-targeted therapy. Patients were randomly assigned in a 1:1 ratio to receive maintenance HER2-targeted and endocrine therapies with or without palbociclib. The primary end point was investigator-assessed progression-free survival. Secondary end points included the objective response, clinical benefit, safety, and overall survival. RESULTS:A total of 518 patients underwent randomization: 261 were assigned to receive palbociclib and 257 to receive standard therapy. At a median follow-up of 53.5 months, patients in the palbociclib group had significantly longer progression-free survival than those in the standard-therapy group (median duration, 44.3 months vs. 29.1 months; hazard ratio for disease progression or death, 0.75; 95% confidence interval, 0.59 to 0.96; two-sided P = 0.02). Grade 3 and 4 adverse events, predominantly from neutropenia, occurred in 79.7% and 10.0% of the patients, respectively, in the palbociclib group, as compared with 30.6% and 3.6% of the patients, respectively, in the standard-therapy group. CONCLUSIONS:The addition of palbociclib to maintenance anti-HER2 and endocrine therapies led to a significant improvement in progression-free survival over standard therapy, with increased toxic effects, mainly neutropenia. (Funded by Pfizer and others; PATINA ClinicalTrials.gov number, NCT02947685.).

TPS1129 Background: Substantial improvement in survival outcomes has been achieved with cyclin-dependent kinase (CDK) 4/6 inhibitors plus endocrine therapy (ET) in patients with hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2−) advanced/metastatic breast cancer (BC); however, resistance to this therapy ultimately occurs. PF-07220060 is an oral, highly potent, selective, next generation inhibitor of CDK4 with sparing of CDK6. A first-in-human phase 1/2a study evaluated PF-07220060 (300/400 mg BID) plus ET in patients with HR+/HER2− advanced/metastatic BC who progressed on a prior CDK4/6 inhibitor plus ET (n = 26). At the data cutoff date of November 1, 2022, in patients with measurable disease (n = 21), 6 (29%) had confirmed objective response (OR) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, and 11 (52%) had a clinical benefit response (CBR). Of all patients (n = 26), median progression-free survival (PFS) was 24.7 weeks, and 8 (31%) patients continued treatment without progression for 60 or more weeks (1). Methods: This international (29 countries; 356 proposed sites), phase 3, open-label, randomized, parallel-group clinical trial will evaluate whether PF-07220060 plus fulvestrant improves clinical outcomes compared with the investigator-chosen therapies in adult female and male patients with HR+/HER2− advanced/metastatic BC with progression after prior therapy of CDK4/6 inhibitor plus a nonsteroidal aromatase inhibitor.Key eligibility criteria include advanced/metastatic BC with measurable disease or non-measurable bone-only disease, documented HR+/HER2− status, and progressive disease/recurrence during or within 12 months after the last dose of prior CDK4/6 inhibitor given in the advanced or adjuvant setting, respectively. One additional prior line of approved treatment in the advanced setting targeting ESR1, PIK3CA, AKT1, PTEN, or BRCA is allowed. Approximately 500 patients will be randomly assigned (1:1) to receive PF-07220060 (orally and continuously in a 28-day cycle) plus fulvestrant (intramuscular injection on days 1 and 15 of cycle 1 and then on day 1 of each cycle thereafter) or investigator’s choice of fulvestrant alone or everolimus plus exemestane, which must be declared before randomization. The primary endpoint is PFS by blinded independent central review, which is defined as the time from the date of randomization to the date of first documented disease progression, as determined per RECIST v1.1, or death due to any cause, whichever occurs first. Secondary objectives include overall survival, OR, duration of response, CBR, safety, patient-reported outcomes, and pharmacokinetics. 1. Yap. JCO. 2023;41:3009. Clinical trial information: NCT06105632 .

TPS1129 Background: Substantial improvement in survival outcomes has been achieved with cyclin-dependent kinase (CDK) 4/6 inhibitors plus endocrine therapy (ET) in patients with hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2−) advanced/metastatic breast cancer (BC); however, resistance to this therapy ultimately occurs. PF-07220060 is an oral, highly potent, selective, next generation inhibitor of CDK4 with sparing of CDK6. A first-in-human phase 1/2a study evaluated PF-07220060 (300/400 mg BID) plus ET in patients with HR+/HER2− advanced/metastatic BC who progressed on a prior CDK4/6 inhibitor plus ET (n = 26). At the data cutoff date of November 1, 2022, in patients with measurable disease (n = 21), 6 (29%) had confirmed objective response (OR) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, and 11 (52%) had a clinical benefit response (CBR). Of all patients (n = 26), median progression-free survival (PFS) was 24.7 weeks, and 8 (31%) patients continued treatment without progression for 60 or more weeks (1). Methods: This international (29 countries; 356 proposed sites), phase 3, open-label, randomized, parallel-group clinical trial will evaluate whether PF-07220060 plus fulvestrant improves clinical outcomes compared with the investigator-chosen therapies in adult female and male patients with HR+/HER2− advanced/metastatic BC with progression after prior therapy of CDK4/6 inhibitor plus a nonsteroidal aromatase inhibitor.Key eligibility criteria include advanced/metastatic BC with measurable disease or non-measurable bone-only disease, documented HR+/HER2− status, and progressive disease/recurrence during or within 12 months after the last dose of prior CDK4/6 inhibitor given in the advanced or adjuvant setting, respectively. One additional prior line of approved treatment in the advanced setting targeting ESR1, PIK3CA, AKT1, PTEN, or BRCA is allowed. Approximately 500 patients will be randomly assigned (1:1) to receive PF-07220060 (orally and continuously in a 28-day cycle) plus fulvestrant (intramuscular injection on days 1 and 15 of cycle 1 and then on day 1 of each cycle thereafter) or investigator’s choice of fulvestrant alone or everolimus plus exemestane, which must be declared before randomization. The primary endpoint is PFS by blinded independent central review, which is defined as the time from the date of randomization to the date of first documented disease progression, as determined per RECIST v1.1, or death due to any cause, whichever occurs first. Secondary objectives include overall survival, OR, duration of response, CBR, safety, patient-reported outcomes, and pharmacokinetics. 1. Yap. JCO. 2023;41:3009. Clinical trial information: NCT06105632 .

Summary of exposure to afuresertib, paclitaxel and carboplatin

Study treatment disposition

AbstractPurpose: Preclinically, AKT kinase inhibition restores drug sensitivity in platinum-resistant tumors. Here the pan-AKT kinase inhibitor afuresertib was given in combination with paclitaxel and carboplatin (PC) in patients with recurrent platinum-resistant epithelial ovarian cancer (PROC) and primary platinum-refractory ovarian cancer (PPROC). Patients and Methods: Part I was a combination 3+3 dose escalation study for recurrent ovarian cancer. Patients received daily continuous oral afuresertib at 50–150 mg/day with intravenous paclitaxel (175 mg/m2) and carboplatin (AUC5) every 3 weeks for six cycles followed by maintenance afuresertib at 125 mg/day until progression or toxicity. Part II was a single-arm evaluation of the clinical activity of this combination in recurrent PROC (Cohort A) or PPROC (Cohort B). Patients received oral afuresertib at the MTD defined in Part I in combination with PC for six cycles, followed by maintenance afuresertib. Primary endpoints were safety and tolerability of afuresertib in combination with PC (Part I, dose escalation), and investigator-assessed overall response rate (ORR) as per RECIST version 1.1 (Part II). Results: Twenty-nine patients enrolled into Part I, and 30 into Part II. Three dose-limiting toxicities of grade 3 rash were observed, one at 125 mg and two at 150 mg afuresertib. The MTD of afuresertib in combination with PC was therefore identified as 125 mg/day. The most common (≥50%) drug-related adverse events observed in Part I of the study were nausea, diarrhea, vomiting, alopecia, fatigue, and neutropenia and, in Part II, were diarrhea, fatigue, nausea, and alopecia. The Part II ORR in the intention to treat patients was 32% [95% confidence interval (CI), 15.9–52.4] by RECIST 1.1 and 52% (95% CI, 31.3–72.2) by GCIG CA125 criteria. Median progression-free survival was 7.1 months (95% CI, 6.3–9.0 months). Conclusions: Afuresertib plus PC demonstrated efficacy in recurrent PROC with the MTD of afuresertib defined as 125 mg/day.

ENESTfreedom is evaluating treatment-free remission (TFR) following frontline nilotinib in patients with chronic myeloid leukemia (CML) in chronic phase. Following our primary analysis at 48 weeks, we here provide an updated 96-week analysis.

TKIs are the standard of care for patients with CML-CP, but some patients are resistant to or intolerant of available TKI therapies. Asciminib (ABL001) is a new TKI that targets the myristoyl pocket of BCR-ABL1 and functions as a potent and selective allosteric inhibitor, in contrast to currently available TKIs (eg, imatinib, nilotinib, dasatinib, bosutinib, ponatinib, radotinib) that target the BCR-ABL1 adenosine triphosphate (ATP) binding site. Asciminib has a resistance mutation profile that differs from those of ATP binding–site TKIs (Wylie AA, et al. Nature. 2017;543:733-737) and has shown clinical activity in an ongoing phase 1 study in patients with CML and resistance to/intolerance of prior TKIs (Hughes TP, et al. Blood. 2016;128 [abstract 625]).

Myelofibrosis (MF) is associated with a variety of burdensome symptoms and reduced survival compared with age-/sex-matched controls. This analysis evaluated the long-term survival benefit with ruxolitinib, a Janus kinase (JAK)1/JAK2 inhibitor, in patients with intermediate-2 (int-2) or high-risk MF.

Background: Clinical studies have demonstrated that ≈ 50% of pts with CML-CP in sustained DMR on long-term tyrosine kinase inhibitor (TKI) therapy can stop treatment and achieve TFR. ENESTfreedom and ENESTop are investigating TFR in pts with sustained DMR on frontline or second-line nilotinib, respectively. Among pts who entered the TFR phase of ENESTfreedom or ENESTop, 98/190 (51.6%) and 73/126 (57.9%), respectively, remained in TFR at 48 wk (primary endpoint); 93 (48.9%) and 67 (53.2%) remained in TFR at 96 wk. As an exploratory objective, these studies are investigating the potential to achieve TFR in pts initially deemed ineligible due to unstable DMR but who achieved stable DMR with additional nilotinib treatment.

Background: The ability to stop TKI therapy without loss of response (ie, TFR) is a new treatment goal for patients (pts) with CML-CP. Reasons for considering TFR include relief from TKI-related adverse effects, family planning, and decreased financial burden. ENESTfreedom and ENESTop have shown durable TFR rates through 96 wk after stopping frontline and second-line nilotinib (NIL), respectively. This analysis evaluated the impact of treatment cessation on overall disease outcomes in these studies.

ENESTfreedom and ENESTop are evaluating TFR (ie, tyrosine kinase inhibitor [TKI] cessation without losing response) after frontline and second-line nilotinib, respectively.

Ruxolitinib, a Janus kinase 1 and 2 (JAK1/2) inhibitor, is the only approved drug for the treatment of intermediate- or high-risk myelofibrosis.[1] In the phase 3 registration trials, ruxolitinib d...

Abstract Background:The Janus kinase (JAK) 1/JAK2 inhibitor ruxolitinib has been evaluated for patients with MF in the phase 3 COMFORT studies. In both trials, ruxolitinib prolonged OS, reduced splenomegaly, and improved MF-related symptoms and quality of life compared with controls. Here, we report the results of an exploratory pooled analysis of OS in the COMFORT studies at 5 years of follow-up. Methods: The double-blind COMFORT-I trial and the open-label COMFORT-II trial were randomized phase 3 studies that evaluated the safety and efficacy of ruxolitinib in patients with intermediate-2 (int-2) or high-risk primary MF (PMF), post-polycythemia vera MF (PPV-MF), or post-essential thrombocythemia MF (PET-MF). The comparator was placebo in COMFORT-I and best available therapy (BAT) in COMFORT-II. The ruxolitinib starting dose was 15 or 20 mg twice daily based on baseline platelet counts (100-200 and >200 × 109/L, respectively); dose modifications were permitted for safety and efficacy. Patients were allowed to cross over to ruxolitinib from the control arm for progressive splenomegaly, defined as a ≥25% increase in spleen volume from baseline (COMFORT-I) or study nadir (COMFORT-II), or select protocol-defined progression events; crossover was mandatory following treatment unblinding in COMFORT-I. OS was a secondary endpoint in both studies and was evaluated in an intent-to-treat (ITT) analysis using a Cox proportional hazard model that estimated the treatment effect stratified by clinical trial and International Prognostic Scoring System (IPSS) risk. The crossover-corrected treatment effect was estimated using a rank-preserving structural failure time (RPSFT) method. Results: Overall, 528 patients were randomized: 301 to ruxolitinib (COMFORT-I, n=155; COMFORT-II, n=146) and 227 to placebo (n=154) or BAT (n=73). All ongoing patients in the control arms crossed over to ruxolitinib by the 3-year follow-up. Patient populations were similar between the two trials and their details were previously published. In the combined ruxolitinib group, 162 patients (53.8%) had high-risk MF and 139 (46.2%) had int-2 risk MF based on IPSS criteria. At the 5-year ITT analysis, 128 patients (42.5%) died in the ruxolitinib group compared with 117 (51.5%) in the control group. The risk of death was reduced by 30% with ruxolitinib compared with control (median OS: ruxolitinib, 63.5 mo; control, 45.9 mo; HR, 0.70; 95% CI, 0.54-0.91; P=0.0065; Figure A). After correcting for crossover using RPSFT, OS advantage was more pronounced for patients originally randomized to ruxolitinib (median OS: ruxolitinib, 63.5 mo; control, 27 mo; HR, 0.35; 95% CI, 0.23-0.59; Figure B). An analysis of OS censoring patients at the time of crossover also demonstrated that ruxolitinib prolonged survival compared with control (median OS: ruxolitinib, 63.5 mo; control, 28.3 mo; HR, 0.53; 95% CI, 0.36−0.78; P=0.0013; Figure C). Among all patients treated with ruxolitinib, those with lower-risk disease had longer survival compared with those with high-risk disease (median OS: int-2, not reached [estimated, 102 mo]; high-risk, 50 mo; HR, 2.86; 95% CI, 1.95-4.20; P<0.0001; Figure D). In a subgroup analysis, OS favored ruxolitinib compared with placebo for patients with int-2 or high-risk MF (data not shown). At 5 years, median OS appeared to favor patients with int-2 (n=58) or high-risk (n=89) PMF who were originally randomized to ruxolitinib compared with historical (Cervantes et al; J Clin Oncol 30:2981-2987) controls (int-2 PMF, not reached [estimated, 70 mo] vs 48 mo; high-risk PMF, 34 vs 27 mo); OS was longer among patients with int-2 vs high-risk PMF (P=0.0003). Subgroup analyses showed that ruxolitinib provided an OS advantage regardless of age (>65 or ≤65 y), sex, disease type (PMF, PPV-MF, PET-MF), risk status (int-2 or high), JAK2V617F mutation status, baseline spleen volume (>10 or ≤10 cm), anemia, white blood cell count (>25 or ≤25 × 109L), or platelet count (>200 or ≤200 × 109/L). Conclusion: Long-term treatment with ruxolitinib up to 5 years prolonged survival in patients with MF compared with BAT or placebo. Corrections for patients who crossed over to ruxolitinib suggested that the separation between ruxolitinib and control OS curves was primarily caused by a delay in ruxolitinib treatment. The results suggest that earlier treatment with ruxolitinib may provide a greater survival advantage for patients with MF. Disclosures Gupta: Incyte Corporation: Consultancy, Research Funding; Novartis: Consultancy, Honoraria, Research Funding. Mesa:Incyte: Research Funding; Ariad: Consultancy; Novartis: Consultancy; Celgene: Research Funding; CTI: Research Funding; Promedior: Research Funding; Galena: Consultancy; Gilead: Research Funding. Vannucchi:Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau. Kiladjian:AOP Orphan: Research Funding; Novartis: Research Funding. Cervantes:AOP Orphan: Membership on an entity's Board of Directors or advisory committees; Baxalta: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Sun:Incyte Corporation: Employment, Equity Ownership. Gao:Incyte Corporation: Employment, Equity Ownership. Dong:Novartis Pharmaceutical Corporation: Employment, Equity Ownership. Naim:Incyte Corporation: Employment, Equity Ownership. Gopalakrishna:Novartis Pharma AG: Employment, Equity Ownership. Harrison:Incyte Corporation: Honoraria, Speakers Bureau; Baxaltra: Consultancy, Honoraria, Speakers Bureau; Gilead: Honoraria, Speakers Bureau; CTI Biopharma: Consultancy, Honoraria, Speakers Bureau; Shire: Honoraria, Speakers Bureau; Novartis: Consultancy, Honoraria, Other: travel, accommodations, expenses, Research Funding, Speakers Bureau.

TPS7080 Background: Myelofibrosis (MF) is a clonal hematologic neoplasm characterized by bone marrow fibrosis, splenomegaly, anemia, and debilitating constitutional symptoms. Currently, most patients (pts) without overt splenomegaly or disease-related symptoms or cytosis are managed through a “watch and wait” strategy treating only when signs of the disease are present. However, recent evidence has suggested that pts with high molecular risk (HMR) mutations (ASXL1, EZH2, SRSF2, and IDH1/2) experience a more aggressive form of disease (Guglielmelli, et al. Leukemia 2014). This subset of pts might be candidates for earlier intervention. Ruxolitinib (Rux), a JAK1/2 inhibitor approved in advanced MF, has been shown to improve symptoms and splenomegaly, and prolong survival in 2 phase 3 COMFORT studies. The ReTHINK study investigates the potential benefits of Rux in pts with early nonsymptomatic MF who harbor at least 1 HMR mutation and for whom Rux is currently not used. Methods: The ReTHINK study is a multicenter, randomized (1:1), double-blind, placebo-controlled, phase 3 study investigating the efficacy and safety of Rux (10 mg twice daily) in early MF pts with HMR mutations. The planned enrollment is 320 pts. Key inclusion criteria, in addition to a mutation in at least 1 of 5 HMR genes, include criteria for early MF with nonpalpable spleen or palpable spleen ≤ 5 cm and MF 7-item symptom scale (MF-7) score of ≤ 15 (with each individual symptom score of ≤ 3). Prior treatment with Rux or other JAK inhibitors, eligibility for allogeneic stem cell transplantation, inadequate liver function, and severely impaired renal function are key exclusion criteria. Primary objective is to evaluate clinical benefit of Rux in delaying progression of MF from early disease to more advanced disease stages. Primary analysis will be performed at 90 progression-free survival (PFS-1) events as assessed via the protocol-defined criteria for disease progression. Other objectives include evaluation of PFS beyond the first occurrence of disease progression (PFS-2), time to progression, change in spleen length and volume from baseline, change in symptoms using MF-7, EQ-5D, and PGIC, safety, and overall survival. Clinical trial information: NCT02598297.

Background: The phase 3 COMFORT trials demonstrated that the Janus kinase (JAK)1/JAK2 inhibitor RUX reduces spleen volume, prolongs overall survival (OS), and improves MF−related symptoms and measures of quality of life in patients with intermediate-2 or high-risk MF, compared with either placebo (COMFORT-I) or best available treatment (BAT; COMFORT-II). Many patients with MF are anemic or transfusion-dependent; the impact of these features on clinical outcomes is unknown. We evaluated the relationship between transfusion requirement and clinical outcomes in patients treated with RUX in the COMFORT studies.

2551 Background: Patients (pts) with ovarian cancer (OC) often develop resistance to standard medical treatment (Rx) with platinum-taxane chemotherapy. Preclinical studies have shown that intra-nuclear activation of AKT by DNA-dependent protein kinase inhibits cisplatin-mediated DNA damage in OC cell lines, which is reversible through AKT inhibition. The following study investigates whether the oral pan-AKT inhibitor afuresertib can restore sensitivity to platinum Rx and reverse acquired resistance to standard Rx in recurrent OC. Methods: In phase I, the maximum tolerated dose (MTD) was investigated; pts with recurrent OC were treated with afuresertib (orally qd) at doses escalating from 50 to 150 mg combined with paclitaxel (IV 175 mg/m2) and carboplatin (AUC 5) q3w for ≤ 6 cycles followed by afuresertib maintenance until progression/toxicity. Phase II investigated efficacy and safety of afuresertib at MTD plus paclitaxel and carboplatin followed by afuresertib maintenance. Pts were split into two cohorts: platinum resistant (PTR) or platinum refractory pts. Results: Phase I enrolled 29 pts; dose-limiting toxicities (DLTs) were reported in 1 pt from the 125 mg cohort (G3 rash [n = 1]) and 2 pts from the 150 mg cohort (G3 rash in both pts with concurrent G2 febrile neutropenia and G2 lip swelling in 1 pt). The MTD of afuresertib was established as 125 mg. Phase II enrolled 30 heavily pre-treated pts (median time since diagnosis = 2.1 y; median prior Rx lines = 3); 28 were PTR and 2 were platinum refractory. Tolerability of Rx was consistent with findings in phase I; G3/4 AEs included diarrhea (20%), fatigue (10%), rash (10%), vomiting (7%), and nausea (3%). Overall response rate (ORR) per RECIST v1.1 for pts in the platinum-resistant cohort was 32.1% (95% CI: 15.9–52.4) and median PFS was 7.1 months (95% CI: 6.3–9.0). ORR per GCIG CA125 in evaluable pts was 52.0% (n = 25; 95% CI: 31.3–72.2). Ad hoc analyses showed ORR to correlate with duration of sensitivity to prior platinum Rx and platinum-free intervals. Conclusions: An MTD of 125 mg afuresertib was established for the Rx of pts in combination with paclitaxel and carboplatin. Combination Rx was well tolerated and showed promising activity in pts with PTR OC. Clinical trial information: NCT01653912.

BACKGROUND: Ruxolitinib (RUX), a JAK1/JAK2 inhibitor, has demonstrated rapid and durable reductions in splenomegaly, improvements in symptoms and quality-of-life measures, and prolonged survival in patients (pts) with intermediate-2 (int-2) or high risk myelofibrosis (MF) in COMFORT trials. Phosphatidylinositol-3-kinase (PI3K) is a downstream regulator of the JAK-STAT pathway and constitutive PI3K activation has been implicated in MF. Preliminary data suggest that inhibition of PI3K/mTOR pathway has beneficial effects in MF. The aim of this study (HARMONY) is to evaluate the safety and efficacy of combining RUX and buparlisib, a potent oral pan-class I PI3K inhibitor, in pts with int or high-risk MF.

Introduction: Anemia is a sign of disease progression and a key prognostic factor in myelofibrosis (MF). In the phase 3 COMFORT studies, ruxolitinib, a Janus kinase (JAK) 1/JAK2 inhibitor, demonstrated improved overall survival compared with placebo and best available therapy in patients with intermediate 2 or high-risk MF (per the International Prognostic Scoring System [IPSS]). Ruxolitinib treatment was associated with dose-dependent increases in cytopenias that occurred mostly in the first 12 weeks of therapy and were manageable with dose adjustments and red blood cell (RBC) transfusions. The objective of this analysis was to evaluate the differential impact of disease-related anemia (anemia at baseline) and anemia occurring after initiation of ruxolitinib therapy on overall survival (OS) in patients with MF.

Anemia is considered a negative prognostic risk factor for survival in patients with myelofibrosis. Most patients with myelofibrosis are anemic, and 35–54 % present with anemia at diagnosis. Ruxolitinib, a potent inhibitor of Janus kinase (JAK) 1 and JAK2, was associated with an overall survival benefit and improvements in splenomegaly and patient-reported outcomes in patients with myelofibrosis in the two phase 3 COMFORT studies. Consistent with the ruxolitinib mechanism of action, anemia was a frequently reported adverse event. In clinical practice, anemia is sometimes managed with erythropoiesis-stimulating agents (ESAs). This post hoc analysis evaluated the safety and efficacy of concomitant ruxolitinib and ESA administration in patients enrolled in COMFORT-II, an open-label, phase 3 study comparing the efficacy and safety of ruxolitinib with best available therapy for treatment of myelofibrosis. Patients were randomized (2:1) to receive ruxolitinib 15 or 20 mg twice daily or best available therapy. Spleen volume was assessed by magnetic resonance imaging or computed tomography scan.