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Background: CDK4/6i combined with ET improves survival for pts with HR+, HER2- MBC. However, biomarkers to predict efficacy and resistance are needed. We hypothesized that a comprehensive next-generation sequencing (NGS)-based liquid biopsy assessment of ctDNA mutation and copy number analysis may identify novel prognostic and predictive biomarkers. Methods: We collected serial blood for ctDNA testing from the 51 pts with HR+, HER2- MBC enrolled in the Alt Dose Palbo trial (NCT03007979), a single-arm phase II study of palbociclib plus letrozole or fulvestrant at 5 days on/2 days off weekly schedule as the first- or second-line ET. The median follow up was 38.2 months at data cutoff for this analysis. Plasma collected at baseline (BL) from all 51 pts, at progression (PD) from all 20 pts who have progressed, and at additional interim timepoints from 2 pts to explore longitutinal changes, with paired germline DNA, were subjected to the PredicineWES+ assay and low-pass whole-genome sequencing (lpWGS). The PredicineWES+ assay provides deep sequencing of 600 genes in the PredicineATLAS panel combined with whole-exome sequencing (WES) of all exonic regions of 20,000 genes enabling genome-wide detection of somatic single nucleotide variation (SNV), indels, copy number variation (CNV) and determination of bTMB. LpWGS offers an unbiased and high-throughput assessment of CNVs and tumor fraction in cell free DNA to derive bCNB. Statistical associations of bTMB, bCNB, and individual alterations with clinical benefit (CB), defined as no PD at 24 weeks by RECIST 1.1, and progression-free survival (PFS) were examined by Fisher’s exact test, Kaplan-Meier analysis, and Cox model. P values were adjusted to control false discovery rate (FDR). Results: The BL median bTMB was 1.6 mutations per megabase pair [IQR 0.6-3.5]. Pts with CB (N=41, 80%) had significantly lower bTMB scores (median [IQR] 1.2 [0.6-2.6] vs. 8.3 [2.4-21.4], (P Citation Format: Andrew Davis, Jingqin Luo, Tiantian Zheng, Lu Tan, Amy Wang, Rama Suresh, Foluso Ademuyiwa, Caron Rigden, Timothy Rearden, Katherine Clifton, Katherine Weilbaecher, Ashley Frith, Pavan K Tandra, Tracy Summa, Brittney Haas, Shana Thomas, Leonel Hernandez-Aya, Lindsay Peterson, Shujun Luo, Bonnie L King, Shidong Jia, Jianjun Yu, Pan Du, Jairam Krishnamurthy, Cynthia X Ma, C Dai. Blood tumor mutational burden (bTMB) and blood copy number burden (bCNB) by genome-wide circulating tumor DNA (ctDNA) assessment predict outcome and resistance in hormone-receptor positive (HR+), HER2 negative (HER2-) metastatic breast cancer (MBC) patients (pts) treated with CDK4/6 inhibitor (CDK4/6i) [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P2-07-01.

PURPOSE: Patients with triple negative breast cancer (TNBC) who do not achieve pathological complete response (pCR) following neoadjuvant chemotherapy have a high risk of recurrence and death. Molecular characterization may identify patients unlikely to achieve pCR. This neoadjuvant trial was conducted to determine the pCR rate with docetaxel and carboplatin, and to identify molecular alterations and/or immune gene signatures predicting pCR. EXPERIMENTAL DESIGN: Patients with clinical stages II/III TNBC received 6 cycles of docetaxel and carboplatin. The primary objective was to determine if neoadjuvant docetaxel and carboplatin would increase the pCR rate in TNBC compared to historical expectations. We performed whole exome sequencing (WES) and immune profiling on pre-treatment tumor samples to identify alterations that may predict pCR. Thirteen matching on-treatment samples were also analyzed to assess changes in molecular profiles. RESULTS: Fifty-eight of 127 (45.7%) patients achieved pCR. There was a non-significant trend towards higher mutation burden for patients with residual cancer burden (RCB) 0/I versus RCB II/III (median 80, versus 68 variants, p 0.88). TP53 was the most frequently mutated gene, observed in 85.7% of tumors. EGFR, RB1, RAD51AP2, SDK2, L1CAM, KPRP, PCDHA1, CACNA1S, CFAP58, COL22A1, and COL4A5 mutations were observed almost exclusively in pre-treatment samples from patients who achieved pCR. Seven mutations in PCDHA1 were observed in pre-treatment samples from patients who did not achieve pCR. Several immune gene signatures including IDO1, PD-L1, interferon gamma signaling, CTLA4, cytotoxicity, tumor inflammation signature, inflammatory chemokines, cytotoxic cells, lymphoid, PD-L2, exhausted CD8, Tregs, and immunoproteosome were upregulated in pre-treatment samples from patients who achieved pCR. CONCLUSIONS: Neoadjuvant docetaxel and carboplatin resulted in a pCR of 45.7%. WES and immune profiling differentiated patients with and without pCR. TRIAL REGISTRATION: Clinical trial information: NCT02124902, Registered 24 April 2014, & NCT02547987, Registered 10 September 2015.

Background: With advances in next generation sequencing (NGS) and now approved targeted therapy in breast cancer, genomic testing to identify potentially actionable mutations has become a common practice in patients (pts) with advanced breast cancer using both ctDNA and traditional tissue-based assays. Less is known regarding physician practice patterns in obtaining NGS testing and the practical implications of testing in older adults with breast cancer.Methods: Pts with advanced breast cancer underwent molecular profiling using a plasma-based ctDNA NGS assay (Guardant360® or Tempus®) between 5/2015 and 5/2020 at Siteman Cancer Center. Pts with advanced breast cancer who underwent genomic profiling using a tissue-based NGS assay (Tempus®) between 12/2017 and 5/2020 at this institution were also included. Clinicopathological histories were obtained from the medical record. Correlations were examined using a Fisher’s exact test.Results: During 5/15-5/20, 244 pts underwent ctDNA testing and 147 pts had a tissue-based NGS assay performed. There was no significant difference between the number of pts ≥ 65 years-old who underwent ctDNA testing (n=78, 32.0%) and tissue testing (n=37, 25.2%). There was no statistically significant difference between date of metastatic diagnosis and date of NGS testing between the older and younger cohorts. In pts who underwent tissue-based NGS testing, there was no significant difference between site of tissue tested (distant recurrence vs local) in the older and younger cohorts. The most common clinical managements following both ctDNA and tissue-based testing are presented in Table 1. Out of the 391 pts who underwent testing, 27 pts had both ctDNA and tissue-based NGS performed. Pts ≥ 65 were less likely to have both assays performed (n=3, 11.1%; p Conclusion: Older adults, who are typically less likely to be included in clinical trials, may still benefit from NGS to reveal potentially targetable mutations. It is reassuring in our cohort that older adults had ctDNA and tissue-based NGS performed at similar rates as part of standard of care treatment. The clinical management following NGS testing was also not significantly different in the older adult cohort. Older adults were less likely to have both tissue and ctDNA testing performed however, given the high concordance rates between tests, this may be less clinically relevant. Table 1clinical management following NGS testing≥65 years-old Citation Format: Katherine K Clifton, Jingqin Luo, Yu Tao, Jennifer Saam, Thereasa Rich, Timothy Rearden, Anna Roshal, Ashley Frith, Caron Rigden, Foluso Ademuyiwa, Katherine Weilbaecher, Leonel Hernandez Aya, Lindsay Peterson, Nusayba Bagegni, Rama Suresh, Ron Bose, Tanya Wildes, Mateusz Opyrchal, Cynthia Ma. Next generation sequencing (NGS) in older adults with breast cancer using tissue-based and circulating tumor DNA (ctDNA) assays [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS2-09.

Palbociclib 3-weeks-on/1-week-off, combined with hormonal therapy, is approved for hormone receptor positive (HR+)/HER2-negative (HER2−) advanced/metastatic breast cancer (MBC). Neutropenia is the most frequent adverse event (AE). We aim to determine whether an alternative 5-days-on/2-days-off weekly schedule reduces grade 3 and above neutropenia (G3 + ANC) incidence. In this single-arm phase II trial, patients with HR+/HER2− MBC received palbociclib 125 mg, 5-days-on/2-days-off, plus letrozole or fulvestrant per physician, on a 28-day cycle (C), as their first- or second-line treatment. The primary endpoint was G3 + ANC in the first 29 days (C1). Secondary endpoints included AEs, efficacy, and serum thymidine kinase 1 (sTK1) activity. At data-cutoff, fifty-four patients received a median of 13 cycles (range 2.6–43.5). The rate of G3 + ANC was 21.3% (95% CI: 11.2–36.1%) without G4 in C1, and 40.7% (95% CI: 27.9–54.9%), including 38.9% G3 and 1.8% G4, in all cycles. The clinical benefit rate was 80.4% (95% CI: 66.5–89.7%). The median progression-free survival (mPFS) (95% CI) was 19.75 (12.11–34.89), 33.5 (17.25–not reached [NR]), and 11.96 (10.43–NR) months, in the overall, endocrine sensitive or resistant population, respectively. High sTK1 at baseline, C1 day 15 (C1D15), and C2D1 were independently prognostic for shorter PFS (p = 9.91 × 10−4, 0.001, 0.007, respectively). sTK1 decreased on C1D15 (p = 4.03 × 10−7), indicating target inhibition. Rise in sTK1 predicted progression, with the median lead time of 59.5 (inter-quartile range: −206.25–0) days. Palbociclib, 5-days-on/2-days-off weekly, met its primary endpoint with reduced G3 + ANC, without compromising efficacy. sTK1 is prognostic and shows promise in monitoring the palbociclib response. ClinicalTrials.gov#: NCT3007979.

e21694 Background: Nintedanib is a small molecule tyrosine kinase inhibitor targeting VEGFR1-3, PDGFR and FGFR. The purpose of the study was to evaluate the response rate for patients with advanced non-small cell lung cancer (NSCLC) with mutations in TP53, VEGFR1-3, PDGFR-A, PDGFR-B, and FGFR1-3 treated with nintedanib as part of an open label, single arm pilot study. Methods: Patients with advanced NSCLC previously treated with platinum-doublet chemotherapy with ECOG PS≤1 and adequate organ function were enrolled. Exclusion criteria included cavitary or necrotic tumors with invasion of major blood vessels, history of recent thromboembolic events, predisposition to bleeding or thrombosis, myocardial infarction and weight loss > 10% within past 6 months. Nintedanib was administered at a dose of 200 mg orally twice daily during each 28-day cycle until disease progression or unacceptable toxicity. Response assessments were performed every 8 weeks. The primary endpoint was overall response (ORR) by RECIST 1.1. Secondary endpoints included progression-free survival (PFS) and correlating outcomes with specific mutations. Results: Between 5/7/2015 and 11/15/2019, 20 patients were enrolled to study. The median age was 66 years, 15/20 (75% were females), 17/20 (85%) had received prior immunotherapy and 11/20 (55%) had received at least three prior lines of systemic therapy. The ORR was 15% with 3/20 partial responses (PR), while 12 patients had stable disease (SD), with disease control (PR+SD≥16 weeks) rate of 60% (12/20). The median progression-free survival and median overall survival were 18 weeks (95% CI: 8-31) and 48 weeks (95% CI:15-56) respectively. All three responders had a TP53 mutation and had received prior immunotherapy. There were nine grade 3 events including transaminitis in 20%, while one patient each (5%) experienced hyperbilirubinemia, anorexia, fatigue, hypertension, and nausea. Grade 4 events included transaminitis (10%) and cerebral edema (5%). There was one grade 5 cardiac event, which was unrelated to nintedanib. Conclusions: In this pilot study in heavily pretreated and molecularly selected patients with metastatic NSCLC, nintedanib showed modest activity. Clinical trial information: NCT02299141.

The optimal hemoglobin concentration at which to initiate erythropoietic therapy for chemotherapy-induced anemia (CIA) is not well defined. This randomized, open-label, multicenter study evaluated the ability of darbepoetin alfa (300 μg every 3 weeks) to maintain hemoglobin levels ≥10g/dl in patients with CIA (hemoglobin ≥10.5 g/dl and ≤12.0 g/dl) randomized 1:1 to an immediate-intervention group (received darbepoetin alfa immediately) or observation group (received darbepoetin alfa if hemoglobin fell to

PURPOSE: To evaluate the disease-free survival (DFS) and overall survival (OS), prognostic factors, and treatment-related mortality of women with stage IIIB inflammatory breast cancer (IBC) treated with combined modality therapy (CMT) and high-dose chemotherapy (HDCT) with autologous stem-cell transplantation. PATIENTS AND METHODS: Between 1989 and 1997, 47 consecutive patients with stage IIIB IBC were treated with CMT and HDCT and were the subject of this retrospective analysis. Chemotherapy was administered to all patients before and/or after definitive surgery. Neoadjuvant and adjuvant chemotherapy was administered to 33 and 34 patients, respectively, and 20 patients received both. All patients received HDCT with autologous stem-cell transplantation, and 41 patients received locoregional radiation therapy. Tamoxifen was prescribed to patients with estrogen receptor (ER)–positive cancer. RESULTS: The mean duration of follow-up from diagnosis was 30 months (range, 6 to 91 months) and from HDCT was 22 months (range, 0.5 to 82 months). At 30 months, the Kaplan-Meier estimates of DFS and OS from diagnosis were 57.7% and 59.1%, respectively. At 4 years, the Kaplan-Meier estimates of DFS and OS from diagnosis were 51.3% and 51.7%, respectively. In a multivariate analysis, the only factors associated with better survival were favorable response to neoadjuvant chemotherapy (P = .04) and receipt of tamoxifen (P = .06); however, the benefit of tamoxifen was only demonstrated in patients with ER-positive breast cancer. At last follow-up, 28 patients (59.6%) were alive and disease-free. Seventeen patients (36.2%) developed recurrent breast cancer. Seventeen patients died: 15 from disease recurrence and two (4.2%) from treatment-related mortality due to HDCT. CONCLUSION: In this analysis, the early results of treatment with CMT and HDCT compare favorably with other series of patients with stage IIIB IBC treated with CMT alone. These outcomes must be confirmed with longer follow-up and controlled studies.

PURPOSE The goals of this study were to define the efficacy and toxicity of doxorubicin and dose-escalated cyclophosphamide (Cy) along with granulocyte colony-stimulating factor (G-CSF) in the treatment of hormone-refractory prostate cancer (HRPC), to determine the maximal-tolerated dose (MTD) of Cy in this regimen, and to evaluate the impact of prior pelvic irradiation (XRT) on MTD and toxicity. PATIENTS AND METHODS Thirty-five patients were treated every 21 days with fixed-dose doxorubicin (40 mg/m2) and Cy 800 to 2,000 mg/m2 (in a cohort dose-escalation schema) along with G-CSF. RESULTS Five of 15 patients (33%) with measurable disease obtained an objective response. Sixteen of 35 patients (46%) had a greater than 50% decrease in prostate-specific antigen (PSA) level (95% confidence interval [CI], 28.8% to 63.4%). Ten of 35 patients (28.6%) had a greater than 75% decrease in PSA level. The median survival time was 11 months. The median survival duration of patients with a greater than 50% decrease in PSA level was 23 months, versus a median survival time of 7 months in patients without a PSA response (P = .02). Although 33% of cycles were associated with grade 4 neutropenia, febrile neutropenia occurred in only 7.8% of all cycles. Thrombocytopenia and anemia were rare. Nonhematologic toxicity was minimal. Patients who had received prior pelvic XRT had a lower Cy MTD, but their hematologic toxicity was not appreciably different. CONCLUSION This is a well-tolerated, active regimen for the treatment of HRPC. Toxicity was not different in patients with prior pelvic XRT, although these patients had a lower MTD.

19501 Background: Chemotherapy-induced anemia (CIA) can be effectively treated with darbepoetin alfa (DA) using different dosing schedules. Since chemotherapy (CTX) regimens involve various dosing schedules, the ability to synchronize DA dose with CTX could be beneficial. Methods: This phase 2, 25-week (wk), randomized, open-label study compares the efficacy and safety of DA administered using an extended dose schedule (EDS) (every 2 wks [Q2W] or every 3 wks [Q3W]) vs weekly (QW) dosing in patients (pts) with CIA. Pts were randomly assigned to receive DA EDS (either 300 mcg Q2W [with CTX QW, Q2W, or Q4W] or 500 mcg Q3W [with CTX Q3W]) vs 150 mcg DA QW (with CTX QW, Q2W, Q3W, or Q4W). Randomization was stratified by length of CTX cycle, screening hemoglobin (Hb) (< 10 vs = 10 g/dL), and type of cancer (lung/gynecological vs other cancers). The primary endpoint was the change in Hb from baseline (BL) to wk 13; other endpoints included the change in Hb from BL to end of study (EOS), percentage of pts with = 1 transfusion (TFN) from BL to wk 13 and EOS, and safety. Results: Final data for the total 25-wk study period will be presented. Results from a planned interim analysis for all pts who were enrolled in the study and received = 1 dose of DA (n = 752) are shown for wk 13 endpoints (Table). The groups had similar mean change in Hb from BL to wk 13, with a difference (QW minus EDS) (95% CL) of 0.2 (-0.1, 0.4) g/dL. The % pts who achieved target Hb were also similar (difference [95% CL] = 0 [-7, 6]). At the time of the interim analysis, the incidence and types of adverse events were similar between the groups. Ten (3%) EDS and 15 (4%) QW pts had thromboembolic events, 5 (1%) EDS and 2 (1%) QW pts had cerebrovascular accidents, and 19 (5%) EDS and 22 (6%) QW pts had died. Conclusions: This is the first trial synchronizing DA dosing (Q2W and Q3W) with CTX schedules. The interim results suggest that DA administered once per CTX cycle is well-tolerated and efficacious in these patients. [Table: see text] No significant financial relationships to disclose.

Cancer pts with CIA may experience decreased quality of life (QOL) and may require red blood cell transfusions (TFNs). DA increases hemoglobin (Hb) to levels recommended by practice guidelines (11 to 13g/dL), thereby reducing TFN requirements and improving QOL. With chemotherapy (CTX) regimens involving various dosing intervals, being able to synchronize DA dose with CTX could be beneficial. This ongoing phase 2, 25-wk, randomized, open-label, multicenter trial compares the efficacy of DA extended dosing schedule (EDS) administration (every 2 wks [Q2W] or every 3 wks [Q3W]) with DA administered weekly (QW) in pts with CIA. Eligible pts were ≥18 years, had nonmyeloid malignancies, were anemic (Hb Table QW EDS n=245 n=242 *Least squares mean; **Last value carried forward; KM: Kaplan-Meier. Mean (SD) Age, yrs 61.9 (12.8) 62.6 (13.2) Most common tumor type (%) Breast (27) Breast (31) % Pts with stage IV cancer 51 52 Mean (SD) BL Hb (g/dL) 10.1 (0.9) 10.2 (0.8) Mean* (99.9%CL) change in Hb (BL-wk 13) [n] (LVCF**) (g/dL) 1.0 (0.7,1.3) [244] 0.9 (0.5,1.2) [241] KM% (99.9%CL) pts who achieved target Hb (≥11g/dL) [n] 78 (68,89) [210] 76 (65,87) [215] Crude% (99.9%CL) pts who achieved target Hb (≥11g/dL) [n] 70 (59,80) [210] 64 (54,75) [215] Mean (SD) Hb after achieving target (g/dL) [n] 11.6 (0.8) [182] 11.7 (0.7) [166] KM% (99.9%CL) pts who had TFNs [n] 21 (12,29) [245] 22 (13,31) [242] Mean* (SE) change in FACT-F [n] 1.6 (0.85) [161] 2.7 (0.84) [168]

Background: We recently reported final results of a randomized, open-label, multicenter study assessing the efficacy of DA (Aranesp®) 300 mcg Q3W (Rearden et al, ASCO 2004). In this study of 201 pts, pts with grade 1 anemia were treated early with DA (n=102; early group) compared with pts treated late after developing grade 2/3 anemia (ie, hemoglobin [Hb] < 10 g/dL; n=99; observation/late intervention group [obs]). When pts were untreated in the obs group, Hb declined. DA treatment maintained Hb within the NCCN Hb target range for pts in the early group and increased Hb once administered in the obs group. The objective of this analysis was to explore the impact of declining Hb levels on pt-reported outcomes using the FACT-Fatigue (FACT-F) subscale. Methods: Pts with baseline (BL) Hb ≥10.5 and ≤12 g/dL were randomized 1:1 to either the early or obs group for up to 22 weeks. To analyze pt-reported fatigue, the FACT-F subscale was administered Q3W and at the end of treatment. The FACT-F analysis set included pts who were randomized, received study drug, and had a BL and at least 1 post-BL FACT-F score. Analyses of changes in FACT-F scores during treatment from BL were conducted; missing values were not imputed. Results: In 201 randomized and treated pts, mean BL (SD) Hb was similar for each group, 11.1 (0.7) g/dL for the early and 11.2 (0.6) g/dL for the obs groups. In the early group, mean Hb increased to near 12 g/dL in approximately 7 weeks, and due to dose-withholding rules, remained near 12 g/dL for the remainder of the study. In the obs group, Hb declined to < 10 g/dL in 65% of pts. The FACT-F analysis set included 94 pts in the early group and 86 in the obs group. Mean (SD) FACT-F scores at BL were 31.6 (11.7) for the early group and 27.7 (12.8) for the obs group. With categories of Hb change at the end of treatment, a significant trend towards greater improvements in fatigue with increasing Hb levels was observed in both groups (table). In pts in whom Hb was stabilized or improved, no decrease in fatigue scores was noted. However, when Hb declined (Hb change < 0 g/dL), a statistically significant and clinically meaningful (>3 point change in FACT-F score) increase in fatigue was observed (negative change in FACT-F score). Consistent with previous studies, pts with Hb change > 2 g/dL had clinically and statistically significant improvements in fatigue. Conclusion: In the absence of treatment, most mildly anemic cancer pts receiving ctx are at risk of developing grade 2/3 anemia within approximately 7 weeks. This decline in Hb is associated with a statistically significant and clinically meaningful increase in pt-reported fatigue. Our results indicate that DA 300 mcg Q3W may effectively ameliorate the impact of ctx on Hb levels and consequently prevent a decline in fatigue. Further, Q3W DA may provide benefits associated with less-frequent dosing. Mean (95%CL) Change in FACT-F Scores At End of Treatment By Change in Hb Category Early Obs N=94 N=86 Categories of Hb Change < 0 g/dL −6.2 (−12.9, 0.6) −2.8 (−7.2, 1.5) n=23 n=38 >0 to 2 g/dL 0.9 (−2.2, 4.0) 1.7 (−3.9, 7.3) n=52 n=32 > 2 g/dL 8.3 (3.3, 13.2) 6.4 (0.3, 12.5) n=19 n=16 P -value (Jonckheere-Terpstra Trend Test) 0.0003 0.049

8064 Background: Darbepoetin alfa (DA, Aranesp®) administered Q3W is effective for the treatment of CIA (Kotasek et al, 2003). NCCN guidelines recommend initiating erythropoietic therapy when hemoglobin (Hb) is < 11 g/dL with a suggested target Hb of 11 to 12 g/dL. This study was designed to evaluate the ability of DA to maintain Hb ≥ 10 g/dL in mildly anemic pts (early intervention) and pts who become moderately to severely anemic before treatment (late intervention). Methods: Pts with baseline Hb ≥ 10.5 and ≤ 12 g/dL were randomized 1:1 to early (DA 300 mcg Q3W) or late intervention (treated if Hb ≤ 10 g/dL with DA 300 mcg Q3W) groups for up to 23 weeks. The primary endpoint was the percentage of pts in each group with a Hb drop below 10 g/dL. Patient-reported outcomes included the FACT-Fatigue subscale. Proportion endpoints were calculated using Kaplan-Meier (KM) methods. Results: The study is fully enrolled with 204 pts. Data through week 17 for 201 evaluable pts (99 early and 102 late) were analyzed....

Background Chemotherapy-induced anemia (CIA) is responsive to treatment with erythropoiesis-stimulating agents (ESAs) such as darbepoetin alfa. Administration of ESAs on a synchronous schedule with chemotherapy administration could benefit patients by reducing clinic visits and potentially enhancing on-time chemotherapy delivery. Methods This phase 2, 25-week, open-label study evaluated the noninferiority of darbepoetin alfa administered weekly vs. as an extended dosing schedule (every 2 or 3 weeks) in patients with CIA. Patients were randomized 1:1 to an extended dosing schedule (EDS: darbepoetin alfa 300 μg Q2W if chemotherapy was QW, Q2W, or Q4W or darbepoetin alfa 500 μg Q3W if chemotherapy was Q3W) or weekly (150 μg QW regardless of chemotherapy schedule). Stratification factors included chemotherapy cycle length, screening hemoglobin ( Results Seven hundred fifty-two patients (374 QW patients; 378 EDS patients) received ≥1 dose of darbepoetin alfa and were included in the analysis. Demographics and disease state were similar between groups. Seventy-one percent of patients in the EDS group and 76% in the QW group achieved the target hemoglobin of ≥11.0 g/dL. There was a minimal difference in the primary endpoint of mean change in hemoglobin (baseline to Week 13) between the QW and the EDS groups (-0.04 g/dL; 95% confidence interval: -0.26, 0.17 g/dL). The upper limit of the 95% confidence interval was less than the prespecified limit of Conclusion Darbepoetin alfa, when administered synchronously with chemotherapy, on an EDS appears to be similarly efficacious to darbepoetin alfa weekly dosing with no unexpected adverse events. This study provides prospective data on how multiple dosing regimens available with darbepoetin alfa can be synchronized with chemotherapy administered across a range of dosing schedules. Trial registration ClinicalTrials.gov Identifier NCT00144131.