Purpose The third-generation nonsteroidal aromatase inhibitors (AIs) are increasingly used as adjuvant and first-line advanced therapy for postmenopausal, hormone receptor–positive (HR+) breast cancer. Because many patients subsequently experience progression or relapse, it is important to identify agents with efficacy after AI failure. Materials and Methods Evaluation of Faslodex versus Exemestane Clinical Trial (EFECT) is a randomized, double-blind, placebo controlled, multicenter phase III trial of fulvestrant versus exemestane in postmenopausal women with HR+ advanced breast cancer (ABC) progressing or recurring after nonsteroidal AI. The primary end point was time to progression (TTP). A fulvestrant loading-dose (LD) regimen was used: 500 mg intramuscularly on day 0, 250 mg on days 14, 28, and 250 mg every 28 days thereafter. Exemestane 25 mg orally was administered once daily. Results A total of 693 women were randomly assigned to fulvestrant (n = 351) or exemestane (n = 342). Approximately 60% of patients had received at least two prior endocrine therapies. Median TTP was 3.7 months in both groups (hazard ratio = 0.963; 95% CI, 0.819 to 1.133; P = .6531). The overall response rate (7.4% v 6.7%; P = .736) and clinical benefit rate (32.2% v 31.5%; P = .853) were similar between fulvestrant and exemestane respectively. Median duration of clinical benefit was 9.3 and 8.3 months, respectively. Both treatments were well tolerated, with no significant differences in the incidence of adverse events or quality of life. Pharmacokinetic data confirm that steady-state was reached within 1 month with the LD schedule of fulvestrant. Conclusion Fulvestrant LD and exemestane are equally active and well-tolerated in a meaningful proportion of postmenopausal women with ABC who have experienced progression or recurrence during treatment with a nonsteroidal AI.
182 Background: AA + P added to androgen deprivation therapy (ADT) improves overall survival (OS) in newly diagnosed mCNPC patients (pts). AA has been previously coadministered with P (10 mg QD). As a lower dose of P (5 mg QD) was used in LATITUDE, we conducted additional safety analyses. Methods: 1199 pts with newly diagnosed, high-risk mCNPC (≥ 2 of 3 risk factors: Gleason ≥ 8, ≥ 3 bone lesions, visceral metastases) were randomized 1:1 to AA (1 gm QD) + P (5 mg QD) + ADT or placebos (PBOs) of AA and P + ADT: median treatment duration 24 and 14 mo, respectively. Safety analyses focused on key mineralocorticoid excess (ME)-related adverse events (AEs): hypertension (HTN) and hypokalemia. Results: Increased HTN with 5 mg/d P with AA + ADT (relative risk, 1.6 [95% CI, 1.4-1.9]) was similar to prior studies using 10 mg/d P (COU-AA-301: 1.4 [0.9-2.0]; COU-AA-302: 1.6 [1.2-2.1]). Of Gr 3/4 HTN events, 87% (109/126 [AA + P + ADT]) and 83% (52/63 [PBOs + ADT]) resolved to Gr ≤ 2. There were few cerebrovascular events: AA + P + ADT, 5; PBOs + ADT, 9. The protocol allowed increasing dose of P to 10 mg for ME-related AEs, but most Gr 3/4 HTN events were managed only by supplemental antihypertensives. Prior use of antihypertensives at study entry was predictive of Gr 3/4 HTN in both treatment arms (RR: 1.85; 95% CI, 1.14-3.01). Gr 3/4 hypokalemia increased with AA + P + ADT (10.4% [62/597]) vs PBOs + ADT (1.3% [8/602]); 89% (55/62) and 100% (8/8) of these events improved to Gr ≤ 2. Less than 1% of pts in either arm discontinued therapy for ME-related AEs. Conclusions: In-depth analysis of LATITUDE data confirms the safety of 5 mg/d P with AA + ADT and helps provide practical treatment guidance for managing mCNPC. Clinical trial information: NCT01715285. [Table: see text]
Abstract Background: Breast cancer (BC) is the most common malignancy and one of the leading causes of cancer death in women in Latin America (LATAM). However, the region lacks a unified multinational initiative to investigate BC and to further understand regional disparities. Methods: LATINA (LACOG 0615/MO39485) is the first multinational prospective cohort study designed to describe clinicopathological characteristics, treatment patterns, and outcomes of patients with BC in LATAM. Patients aged ≥18 years diagnosed with primary or recurrent BC in the 12 months preceding site activation were included. Data were collected at enrollment and every 6 months for up to 5 years. We present here the results for clinicopathological and demographic characteristics at BC diagnosis. Multivariable logistic regression was performed to investigate characteristics associated with later diagnosis (stage II/III vs. stage I) and detection method (symptomatic vs. screening). Causal mediation analysis was performed to investigate the detection method as a mediator of the effect of health care provision (public or private) on stage at diagnosis. Results: Between February 2020 and August 2022, 3276 patients from 31 research sites in 10 LATAM countries were included. Most patients in this cohort (72.1%, N=2362) were treated in the public health system. Regarding ethnicity, most patients (91.8%, N=3008) self-identified as Latinos and were White (47.3%, N=1549), American Indian (21.0%, N=689), and Black or Brown (16.6%, N=544). The median age at diagnosis was 54 years (range 23–95), 41.8% (N=1368) were < 50 years of age at BC diagnosis, and 54.1% (N=375) of the American Indian patients were ≤50 years of age. BC subtype distribution was: 43.2% (N=1336) luminal A, 14.3% (N=433) luminal B, 22.9% (N=709) human epidermal growth factor receptor 2-positive (HER2+), and 15.4% (N=477) triple negative. In patients older than 50 years old, most cases were detected with symptoms, particularly in the public health system (63.2%, N=836) vs. 50.5% (N=232) in the private health system, p< 0.0001). This was also the case in Black/Brown (61.6%, N=178) and American Indian patients (89.5%, N=281) vs. White patients (45.6%, N=413) (p< 0.0001). In the public system, 37.7% (N=890) and 31.7% (N=748) of cases were diagnosed at stage II and III vs. 37.6% (N=343) and 26.6% (N=243) of cases in the private system, respectively (p< 0.0001). Users of the public health system had a significantly higher risk of being diagnosed with symptoms vs. screening (adjusted odds ratio [aOR] 3.54, 95% CI 2.17–5.76). Causal mediation analysis showed that the detection method (screening vs. symptomatic) mediated 21.8% (95% CI 1.7%–41.9%, p=0.034) of the effect of health care provision (public or private) on stage at diagnosis. Self-identifying as Black (aOR 2.11, 95% CI 1.29–3.45), age < 40 years (aOR 1.97, 95% CI 1.20–3.23), public health care provision (aOR 2.18, 95% CI 1.32–3.59), and a diagnosis of HER2+ (aOR 1.74, 95% CI 1.20–2.52) or triple-negative BC (aOR 2.34, 95% CI 1.47–3.71) were associated with an increased risk of being diagnosed at a later stage. Conclusions: A significant proportion of new BC diagnoses in LATAM is observed in patients < 50 years of age. Reflecting the low screening coverage throughout the region, most patients detect the disease with symptoms. Stage III BC accounted for 30.3% of new cases, being more common among users of the public health system. Differences in the stage at diagnosis related to health care provision (public or private), ethnicity, and country underscore significant disparities that need to be addressed. Further analyses of these data will help identify factors associated with late diagnosis and support the development of regional corrective health policies. Citation Format: Gustavo Werutsky, Cynthia Villarreal-Garza, Henry Gómez, Juan Manuel Donaire, José Bines, Luis Henrique Fein, Maria Clara Horsburgh, Paula Cabrera-Galeana, Heloísa Resende, Rosa Vasallo Veras, Miriam Raimondo, Ricardo Elías Brugés Maya, Vidal Maria Del Rosario, Yeni Nerón, Ana Maria Donoso, Fernanda B. Damian, José D'Oliveira, Couto Filho, Maria Isabel Alonso, Victoria Costanzo, Tomás Reinert, Adriana Elizabeth Borello, Eduardo Cronenberger, Luis Fein, Marcela Urrego, Enrique Alanya, Jorge Luis Soriano García, Saúl Campos-Gomez, Eduardo A. Richardet, Hugo Castro-Salguero, Felipe Cruz, Diego Gómez, Angel Hernández, Carlos Alberto Farfan Tello, Ronald Rodríguez, Rafaela Jesus, Gustavo Gössling, Carlos Barrios. Clinicopathological Characteristics and Factors Associated With Screening and Late-Stage Diagnosis in Patients With Breast Cancer in Latin America: The LATINA Study (LACOG 0615/MO39485) [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-10-04.
Intravenous paclitaxel (IVpac) is complicated by neuropathy and requires premedication to prevent hypersensitivity-type reactions. Paclitaxel is poorly absorbed orally; encequidar (E), a novel P-glycoprotein pump inhibitor, allows oral absorption.A phase III open-label study comparing oral paclitaxel plus E (oPac + E) 205 mg/m2 paclitaxel plus 15 mg E methanesulfonate monohydrate 3 consecutive days per week versus IVpac 175 mg/m2 once every 3 weeks was performed. Women with metastatic breast cancer and adequate organ function, at least 1 year from last taxane, were randomly assigned 2:1 to oPac + E versus IVpac. The primary end point was confirmed radiographic response using RECIST 1.1, assessed by blinded independent central review. Secondary end points included progression-free survival (PFS) and overall survival (OS).Four hundred two patients from Latin America were enrolled (265 oPac + E, 137 IVpac); demographics and prior therapies were balanced. The confirmed response (intent-to-treat) was 36% for oPac + E versus 23% for IVpac (P = .01). The PFS was 8.4 versus 7.4 months, respectively (hazard ratio, 0.768; 95.5% CI, 0.584 to 1.01; P = .046), and the OS was 22.7 versus 16.5 months, respectively (hazard ratio, 0.794; 95.5% CI, 0.607 to 1.037; P = .08). Grade 3-4 adverse reactions were 55% with oPac + E and 53% with IVpac. oPac + E had lower incidence and severity of neuropathy (2% v 15% > grade 2) and alopecia (49% v 62% all grades) than IVpac but more nausea, vomiting, diarrhea, and neutropenic complications, particularly in patients with elevated liver enzymes. On-study deaths (8% oPac + E v 9% IVpac) were treatment-related in 3% and 0%, respectively.oPac + E increased the confirmed tumor response versus IVpac, with trends in PFS and OS. Neuropathy was less frequent and severe with oPac + E; neutropenic serious infections were increased. Elevated liver enzymes at baseline predispose oPac + E patients to early neutropenia and serious infections (funded by Athenex, Inc; ClinicalTrials.gov identifier: NCT02594371).
Uracil and tegafur (in a molar ratio of 4:1 [UFT]) has proven activity against breast cancer and is delivered in an easy-to-administer oral formulation. Orzel, which combines UFT with the oral biomodulator, calcium folinate, may provide even greater antitumor efficacy against breast cancer. Here, we describe the preliminary results of this phase II trial investigating the feasibility of 250 mg/m2/day of UFT plus 45 mg/day of oral calcium folinate administered to highly pretreated patients with advanced breast cancer. The results indicate a highly tolerable regimen and an overall response rate of 27.8% in a group of poor-prognosis patients. These findings warrant continued investigation.
This study evaluated the efficacy, safety, and immunogenicity of biosimilar pegfilgrastim (PegFilBS) and originator pegfilgrastim (PegFilOR) in patients with stage 2-4 breast cancer.This phase III randomized, multicenter, evaluator-blinded, noninferiority study recruited women with stage 2-4 breast cancer in Argentina who were scheduled to receive chemotherapy. Stratification was based on the breast cancer stage. The primary end point was the duration of severe neutropenia (DSN, noninferiority margin: 1 day) in the first chemotherapy cycle. Secondary end points assessed were incidence of severe neutropenia, grade 3 neutropenia, febrile neutropenia, infections, postchemotherapy hospitalization and duration, and the incidence of adverse drug reactions (ADRs).A total of 120 patients were randomly assigned to receive PegFilBS (58 patients) or PegFilOR (62 patients). Severe neutropenia occurred in 52 of 283 cycles (18.4%) for 27 patients who received PegFilBS and in 48 of 297 cycles (16.2%) for 20 patients who received PegFilOR (P = .48). During the first cycle, severe neutropenia occurred in 16 patients who received PegFilBS (DSN: 0.78 ± 1.53 days) and in 11 patients who received PegFilOR (DSN: 0.53 ± 1.25 days; 95% CI, -0.26 to 0.76 days). In the intention-to-treat analysis, the mean DSN values were 0.90 ± 1.79 days for the PegFilBS group and 0.50 ± 1.21 for the PegFilOR group (95% CI, -0.15 to 0.95 days). No significant differences were observed for the secondary efficacy end points. Three patients experienced seven ADRs in the PegFilBS group while 10 patients experienced 31 ADRs in the PegFilOR group. The most common ADR was myalgia.Relative to PegFilOR, PegFilBS provided noninferior efficacy outcomes in Argentinian women with stage 2-4 breast cancer who were treated using myelosuppressive chemotherapy.
The efficacy and safety of treatment with cabozantinib in combination with nivolumab and ipilimumab in patients with previously untreated advanced renal-cell carcinoma are unknown.
14521 Background: Cetuximab (Erbitux) is a monoclonal antibody directed against EGFR that is active in combination with irinotecan in patients (pts) with mCRC, who have progressed during or after a prior irinotecan therapy. Methods: This open, single-arm phase II Latin American study investigated this combination in pts with EGFR-expressing mCRC progressing on or within 3 months of chemotherapy containing at least 6 weeks (w) of irinotecan-based therapy. The primary objective was to assess the best overall confirmed response rate (RR). Sample size calculations were based on an expected rate of 20% (±8%). Planned enrollment was 100 pts. Secondary objectives were to explore the duration of response (DOR), progression-free survival (PFS) time, the 12-week PFS rate, and overall survival time. Pts were treated with cetuximab (initial dose 400 mg/m 2 then 250 mg/m 2 weekly), plus irinotecan at the same dose and schedule (including dose reductions) as pre-study. Preliminary Results: Of 151 pts from 14 centers screened and in the database, 106 (70%, 3 pts missing) were EGFR-expressing and, of these, 79/106 (75%) were treated on-study. Forty (51%) were male; median age was 59 years [27–82]; 70 (89%) pts had a Karnofsky performance status = 90 and 9 (11%) pts = 80. Nineteen (24%) pts had received = 3 prior treatment regimens, 42 (53%) were previously treated with an oxaliplatin-based regimen for metastatic disease. The confirmed overall RR was 26.6% [17.3–37.7]. Median DOR was 23.9 w [17.1–30], median PFS time was 17.7 w [11.7–18.9], and the 12-week PFS rate was 58% [47–69]. Thirty-three (42%) pts were alive at data cut-off. Median survival was 9.7 months [7.9–13.1]. Treatment was well tolerated with the most common grade 3/4 adverse events including: diarrhea, 20%; neutropenia,10%; acne-like rash, 9%. No grade 3/4 infusion-related reactions were reported. Conclusions: The overall confirmed RRs observed in this heavily pretreated population fully met the expectations for the primary endpoint of this study. LABEL confirmed in a Latin American setting the activity and safety of cetuximab plus irinotecan seen in previous studies. No significant financial relationships to disclose.
