Abemaciclib plus a nonsteroidal aromatase inhibitor as initial therapy for HR+, HER2- advanced breast cancer: Final overall survival results of MONARCH 3.

BACKGROUND: In MONARCH 2, the addition of abemaciclib to fulvestrant significantly improved both progression-free survival (PFS) and overall survival (OS) in patients with HR+, HER2- advanced breast cancer (ABC) with disease progression on prior endocrine therapy (ET). In MONARCH 3, the addition of abemaciclib to a nonsteroidal aromatase inhibitor (NSAI) as initial therapy for HR+, HER2- ABC significantly improved PFS. Here, we present the prespecified final OS results for MONARCH 3. PATIENTS AND METHODS: MONARCH 3 is a randomized, double-blind, phase 3 study of abemaciclib plus NSAI (anastrozole or letrozole) versus placebo plus NSAI in postmenopausal women with HR+, HER2- ABC without prior systemic therapy in the advanced setting. The primary objective was investigator-assessed PFS; OS was a gated secondary endpoint, and chemotherapy-free survival (CFS) was an exploratory endpoint. RESULTS: A total of 493 women were randomized 2:1 to receive abemaciclib plus NSAI (n = 328) or placebo plus NSAI (n = 165). After a median follow-up of 8.1 years, there were 198 OS events (60.4%) in the abemaciclib arm and 116 (70.3%) in the placebo arm (hazard ratio, 0.804; 95% confidence interval [CI], 0.637-1.015; P = 0.0664, non-significant). Median OS was 66.8 versus 53.7 months for abemaciclib versus placebo. In the subgroup with visceral disease (sVD), there were 113 OS events (65.3%) in the abemaciclib arm and 65 (72.2%) in the placebo arm (hazard ratio, 0.758; 95% CI, 0.558-1.030; P = 0.0757, non-significant). Median OS was 63.7 months versus 48.8 months for abemaciclib versus placebo. The previously demonstrated PFS benefit was sustained, and CFS numerically improved with the addition of abemaciclib. No new safety signals were observed. CONCLUSION: Abemaciclib combined with an NSAI resulted in clinically meaningful improvement in median OS (ITT: 13.1 months; sVD: 14.9 months) in patients with HR+ HER2- ABC; however, statistical significance was not reached.

Association of HER2DX with pathological complete response and survival outcomes in HER2-positive breast cancer.

BACKGROUND: The HER2DX genomic test predicts pathological complete response (pCR) and survival outcome in early-stage HER2-positive (HER2+) breast cancer. Here, we evaluated the association of HER2DX scores with (i) pCR according to hormone receptor status and various treatment regimens, and (ii) survival outcome according to pCR status. MATERIALS AND METHODS: Seven neoadjuvant cohorts with HER2DX and clinical individual patient data were evaluated (DAPHNe, GOM-HGUGM-2018-05, CALGB-40601, ISPY-2, BiOnHER, NEOHER and PAMELA). All patients were treated with neoadjuvant trastuzumab (n = 765) in combination with pertuzumab (n = 328), lapatinib (n = 187) or without a second anti-HER2 drug (n = 250). Event-free survival (EFS) and overall survival (OS) outcomes were available in a combined series of 268 patients (i.e. NEOHER and PAMELA) with a pCR (n = 118) and without a pCR (n = 150). Cox models were adjusted to evaluate whether HER2DX can identify patients with low or high risk beyond pCR status. RESULTS: HER2DX pCR score was significantly associated with pCR in all patients [odds ratio (OR) per 10-unit increase = 1.59, 95% confidence interval 1.43-1.77; area under the ROC curve = 0.75], with or without dual HER2 blockade. A statistically significant increase in pCR rate due to dual HER2 blockade over trastuzumab-only was observed in HER2DX pCR-high tumors treated with chemotherapy (OR = 2.36 (1.09-5.42). A statistically significant increase in pCR rate due to multi-agent chemotherapy over a single taxane was observed in HER2DX pCR-medium tumors treated with dual HER2 blockade (OR = 3.11, 1.54-6.49). The pCR rates in HER2DX pCR-low tumors were ≤30.0% regardless of treatment administered. After adjusting by pCR status, patients identified as HER2DX low-risk had better EFS (P < 0.001) and OS (P = 0.006) compared with patients with HER2DX high-risk. CONCLUSIONS: HER2DX pCR score and risk score might help identify ideal candidates to receive neoadjuvant dual HER2 blockade in combination with a single taxane in early-stage HER2+ breast cancer.

Immune microenvironment characterisation and dynamics during anti-HER2-based neoadjuvant treatment in HER2-positive breast cancer.

Despite their recognised role in HER2-positive (HER2+) breast cancer (BC), the composition, localisation and functional orientation of immune cells within tumour microenvironment, as well as its dynamics during anti-HER2 treatment, is largely unknown. We here investigate changes in tumour-immune contexture, as assessed by stromal tumour-infiltrating lymphocytes (sTILs) and by multiplexed spatial cellular phenotyping, during treatment with lapatinib-trastuzumab in HER2+ BC patients (PAMELA trial). Moreover, we evaluate the relationship of tumour-immune contexture with hormone receptor status, intrinsic subtype and immune-related gene expression. sTIL levels increase after 2 weeks of HER2 blockade in HR-negative disease and HER2-enriched subtype. This is linked to a concomitant increase in cell density of all four immune subpopulations (CD3+, CD4+, CD8+, Foxp3+). Moreover, immune contexture analysis showed that immune cells spatially interacting with tumour cells have the strongest association with response to anti-HER2 treatment. Subsequently, sTILs consistently decrease at the surgery in patients achieving pathologic complete response, whereas most residual tumours at surgery remain inflamed, possibly reflecting a progressive loss of function of T cells. Understanding the features of the resulting tumour immunosuppressive microenvironment has crucial implications for the design of new strategies to de-escalate or escalate systemic therapy in early-stage HER2+ BC.

A retrospective, multicenter study of the efficacy of lapatinib plus trastuzumab in HER2-positive metastatic breast cancer patients previously treated with trastuzumab, lapatinib, or both: the Trastyvere study.

PURPOSE: To evaluate the efficacy and safety of lapatinib (L) and trastuzumab (T) combination in HER2-positive metastatic breast cancer (MBC) patients previously treated with T and/or L. MATERIALS AND METHODS: We conducted a retrospective, post-authorized, multicenter study including patients with HER2-positive MBC or locally advanced breast cancer (ABC) treated with the combination of L-T. Concomitant endocrine therapy, as well as brain metastasis and/or prior exposure to L, were allowed. RESULTS: One hundred and fifteen patients from 14 institutions were included. The median age was 59.8 years. The median number of prior T regimens in the advanced setting was 3 and 73 patients had received a prior L regimen. The clinical benefit rate (CBR) was 34.8% (95% CI 26.1-43.5). Among other efficacy endpoints, the overall response rate was 21.7%, and median progression-free survival (PFS) and overall survival were 3.9 and 21.6 months, respectively. Heavily pretreated and ≥ 3 metastatic organ patients showed lower CBR and PFS than patients with a low number of previous regimens and < 3 metastatic organs. Moreover, CBR did not significantly change in L-pretreated compared with L-naïve patients (31.5% versus 40.5% for L-pretreated versus L-naïve). Grade 3/4 adverse events were reported in 19 patients (16.5%). CONCLUSION: The combination of L-T is an effective and well-tolerated regimen in heavily pretreated patients and remains active among patients progressing on prior L-based therapy. Our study suggests that the L-T regimen is a safe and active chemotherapy-free option for MBC patients previously treated with T and/or L.

Preclinical and clinical development of palbociclib and future perspectives

Cyclin-dependent kinases (CDKs) play a key role in cell cycle regulation, which makes them a clear therapeutic target to interfere with cell division and proliferation in cancer patients. Palbociclib, a specific inhibitor of CDK4/6 with outstanding clinical efficacy data and limited toxicity, has been recently approved for the treatment of hormone receptor (HR)-positive human epidermal growth factor receptor 2 (HER2)-negative locally advanced or metastatic breast cancer, either in combination with an aromatase inhibitor or in combination with fulvestrant in women who have received prior endocrine therapy. This review describes the mechanism of action, preclinical experiences and clinical data of palbociclib, with a special focus on integrating this data with the positioning of palbociclib in the current clinical guidelines for advanced HR-positive/HER2-negative breast cancer. Aspects of the ongoing major studies are also presented, as well as future prospects in the development of palbociclib

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Preclinical and clinical development of palbociclib and future perspectives.

Cyclin-dependent kinases (CDKs) play a key role in cell cycle regulation, which makes them a clear therapeutic target to interfere with cell division and proliferation in cancer patients. Palbociclib, a specific inhibitor of CDK4/6 with outstanding clinical efficacy data and limited toxicity, has been recently approved for the treatment of hormone receptor (HR)-positive human epidermal growth factor receptor 2 (HER2)-negative locally advanced or metastatic breast cancer, either in combination with an aromatase inhibitor or in combination with fulvestrant in women who have received prior endocrine therapy. This review describes the mechanism of action, preclinical experiences and clinical data of palbociclib, with a special focus on integrating this data with the positioning of palbociclib in the current clinical guidelines for advanced HR-positive/HER2-negative breast cancer. Aspects of the ongoing major studies are also presented, as well as future prospects in the development of palbociclib.

Circulating tumor cells (CTCs) and cytokeratin 19 (CK19) mRNA as prognostic factors in heavily pretreated patients with metastatic breast cancer.

INTRODUCTION: Circulating tumor cell (CTC) count and cytokeratin 19 (CK19) mRNA expression have a prognostic value for patients with metastatic breast cancer (MBC), but their clinical utility remains controversial. We studied CTC count and CK19 mRNA expression in the peripheral blood samples from heavily pretreated patients with MBC and their correlations with prognosis and response to the subsequent line of therapy. METHODS: This prospective observational study included 67 consecutive patients with MBC who were on progression to systemic therapy, and criteria for a new line of systemic treatment were proposed outside a clinical trial. CTC counts and CK19 mRNA expression were measured by the CellSearch® and RT-PCR methods, respectively, before and after the first cycle of treatment. Progression-free survival (PFS) was defined as the time elapsed between the initiation of the treatment and either the date of clinical or radiological tumor progression or death from any cause or the last follow-up. Cox proportional hazards regression model was used to assess the univariate prognostic value of CTC and CK19 mRNA expression on PFS and Kaplan-Meier estimates. A multivariate Cox model was also used to additionally account for phenotype and visceral disease. RESULTS: The mean age was 60 (range 35-86) years, and the average number of previous treatments was 3 (range 1-10); 42 patients (62.6%) were ER+ and 38 patients (56.7%) had visceral disease. The median PFS rate was 8 months (95% CI: 3.7-8.2). Univariate analyses showed a significant effect of the initial value of CK19 mRNA expression (HR = 2.00; 95% CI: 1.05-3.8; p = 0.03) and for the second value of CTC (HR = 2.18; 95% CI: 1.22-3.9; p = 0.009) but did not reach statistical significance for the initial value of CTC and the second value of CK19 mRNA expression. The estimated PFS rates at 6 and 12 months were 75% and 31% for patients with a low initial value of CK19 mRNA expression and 36% and 10% for those with a high initial value of CK19 mRNA expression, respectively (p: 0.022). Further, the estimated PFS rates at 6 and 12 months were 86% and 65% for patients with a low second value of CTC and 76% and 47% for those with a high second value of CTC, respectively (p: 0.004). In the multivariate analysis adjusted for phenotype, visceral disease, and the last treatment performed, only the effect of the second value of CTC remained significant (HR = 2.7, p = 0.004). CONCLUSIONS: CK19 mRNA expression and CTC count appeared clinically meaningful in pretreated patients with MBC, even when adjusted for phenotype and visceral disease involvement. These results support the use of CK19 and CTC as relevant biomarkers for predicting clinical response in MBC.

A predictive model of pathologic response based on tumor cellularity and tumor-infiltrating lymphocytes (CelTIL) in HER2-positive breast cancer treated with chemo-free dual HER2 blockade.

Background: The presence of stromal tumor-infiltrating lymphocytes (TILs) is associated with increased pathologic complete response (pCR) and improved outcomes in HER2-positive early-breast cancer (BC) treated with anti-HER2-based chemotherapy. In the absence of chemotherapy, the association of TILs with pCR following anti-HER2 therapy-only is largely unknown. Patients and methods: The PAMELA neoadjuvant trial treated 151 women with HER2-positive BC with lapatinib and trastuzumab [and hormonal therapy if hormone receptor (HR)-positive] for 18 weeks. Percentage of TILs and tumor cellularity were determined at baseline (N = 148) and at day 15 (D15) of treatment (N = 134). Associations of TILs and tumor cellularity with pCR in the breast were evaluated. A combined score based on tumor cellularity and TILs (CelTIL) measured at D15 was derived in PAMELA, and validated in D15 samples from 65 patients with HER2-positive disease recruited in the LPT109096 neoadjuvant trial, where anti-HER2 therapy-only was administer for 2 weeks, then standard chemotherapy was added for 24 weeks. Results: In PAMELA, baseline and D15 TILs were significantly associated with pCR in univariate analysis. In multivariable analysis, D15 TILs, but not baseline TILs, were significantly associated with pCR. At D15, TILs and tumor cellularity were found independently associated with pCR. A combined score (CelTIL) taking into account both variables was derived. CelTIL at D15 as a continuous variable was significantly associated with pCR, and patients with CelTIL-low and CelTIL-high scores had a pCR rate of 0% and 33%, respectively. In LPT109096, CelTIL at D15 was found associated with pCR both as a continuous variable and as group categories using a pre-defined cut-off (75.0% versus 33.3%). Conclusions: On-treatment TILs, but not baseline TILs, are independently associated with response following anti-HER2 therapy-only. A combined score of TILs and tumor cellularity measured at D15 provides independent predictive information upon completion of neoadjuvant anti-HER2-based therapy. Clinical trial number: NCT01973660.

High pKDR immunohistochemical expression is an unfavourable prognostic biomarker in patients with advanced colorectal cancer treated with chemotherapy plus bevacizumab

Purpose: To analyse the prognostic role of the immunohistochemical expression of pKDR in patients with advanced colorectal cancer treated with oxaliplatin and fluoropyrimidines combination chemotherapy with or without bevacizumab. Methods: Retrospective multicentre study, carried out at four hospitals in the Valencian Community (Spain). Patients evolution was compared based on the immunohistochemical expression of pKDR, classified using 4 categories: 0 (undetectable), 1 (mild), 2 (moderate) and 3 (high intensity). Patients were divided into two groups for the analysis: group 1 with low expression (0-1) vs. group 2 with high expression (2-3). Results: Histological samples for the pKDR analysis were available for 84 of the 112 patients selected. Seven (8.3 %) had undetectable or mild expression of pKDR (Group 1) and 77 (91.7 %) showed moderate or high expression of pKDR (Group 2). Response rate in Group 1 was 100 %compared to 54.2 % in Group 2 (p = 0.019). Progression-free survival (PFS) (15 vs. 12 months, p = 0.4) and overall survival (OS) (28 vs. 22 months, p = 0.09) were numerically but not significantly higher in patients from Group 1 vs. Group 2. Patients from Group 2 who received bevacizumab presented a significantly higher PFS (13 vs. 11, p = 0.015) and a numerically higher OS (23 vs. 17 months, p = 0.27) than those treated exclusively with chemotherapy. Conclusions: Our results suggest that the absence or low expression of pKDR is associated with a better prognostic profile in patients with advanced colorectal cancer treated with chemotherapy and bevacizumab. Patients with a high pKDR expression benefit from the combination of chemotherapy with bevacizumab (AU)

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High pKDR immunohistochemical expression is an unfavourable prognostic biomarker in patients with advanced colorectal cancer treated with chemotherapy plus bevacizumab.

PURPOSE: To analyse the prognostic role of the immunohistochemical expression of pKDR in patients with advanced colorectal cancer treated with oxaliplatin and fluoropyrimidines combination chemotherapy with or without bevacizumab. METHODS: Retrospective multicentre study, carried out at four hospitals in the Valencian Community (Spain). Patients evolution was compared based on the immunohistochemical expression of pKDR, classified using 4 categories: 0 (undetectable), 1 (mild), 2 (moderate) and 3 (high intensity). Patients were divided into two groups for the analysis: group 1 with low expression (0-1) vs. group 2 with high expression (2-3). RESULTS: Histological samples for the pKDR analysis were available for 84 of the 112 patients selected. Seven (8.3 %) had undetectable or mild expression of pKDR (Group 1) and 77 (91.7 %) showed moderate or high expression of pKDR (Group 2). Response rate in Group 1 was 100 % compared to 54.2 % in Group 2 (p = 0.019). Progression-free survival (PFS) (15 vs. 12 months, p = 0.4) and overall survival (OS) (28 vs. 22 months, p = 0.09) were numerically but not significantly higher in patients from Group 1 vs. Group 2. Patients from Group 2 who received bevacizumab presented a significantly higher PFS (13 vs. 11, p = 0.015) and a numerically higher OS (23 vs. 17 months, p = 0.27) than those treated exclusively with chemotherapy. CONCLUSIONS: Our results suggest that the absence or low expression of pKDR is associated with a better prognostic profile in patients with advanced colorectal cancer treated with chemotherapy and bevacizumab. Patients with a high pKDR expression benefit from the combination of chemotherapy with bevacizumab.

Tailoring the dosing schedule of nab-paclitaxel in metastatic breast cancer according to patient and disease characteristics: Recommendations from a panel of experts.

The choice of chemotherapy for patients with metastatic breast cancer (MBC) depends on disease- and patient-related factors, but there is little guidance on dosing modifications for patients unable to receive the licensed dose. Nab-paclitaxel is a solvent-free form of paclitaxel that uses albumin as a drug carrier and exploits endogenous albumin transport pathways to achieve enhanced drug targeting and tumour penetration with reduced toxicity. It is approved for use at a dose of 260 mg/m(2) every three weeks in adults who have failed first-line treatment for MBC and for whom standard anthracycline-based therapy is not indicated. Emerging data suggest that weekly dosing schedules of nab-paclitaxel may provide clinical benefit in some patients, but the utility of these alternative dosing schedules remains unclear. A panel of breast cancer experts convened to review available literature for nab-paclitaxel in MBC and, taking into account their clinical experience, recommended that alternative dosing schedules may be considered according to the aggressiveness of disease and patient condition as follows: 125 mg/m(2) QW 3/4 (aggressive disease and fit), 100mg/m(2) QW 3/4 (aggressive or indolent disease and unfit). All dosing schedules were considered acceptable for fit patients with indolent disease. These recommendations are based on current evidence, and emerging data from ongoing trials may reinforce or modify the recommendations provided.

SEOM clinical guidelines for the management of metastatic breast cancer 2013

Patients with metastatic breast cancer should be offered comprehensive and personalized medical attention including, but not limited to, psychosocial, supportive and symptom-related interventions. A large number of treatment options are available and several prognostic and predictive factors are useful to identify the best therapeutic options individually (AU)

SEOM clinical guidelines for the management of metastatic breast cancer 2013.

Patients with metastatic breast cancer should be offered comprehensive and personalized medical attention including, but not limited to, psychosocial, supportive and symptom-related interventions. A large number of treatment options are available and several prognostic and predictive factors are useful to identify the best therapeutic options individually.

Chemotherapy-induced nausea and vomiting in clinical practice: impact on patients' quality of life.

BACKGROUND: Chemotherapy-induced nausea and vomiting (CINV) in cancer patients are common symptoms most feared by patients. The aim of this study was to analyze the impact of CINV associated to moderate/highly emetogenous chemotherapy regimens on patients' quality of life (QoL). PATIENTS AND METHODS: Open, multicenter, prospective observational study was performed. Each patient filled out a patient diary for each cycle from the day before chemotherapy and for the next 5 days that included the number of emetic episodes, the intensity of nausea, and QoL evaluation (functional living index-emesis questionnaire). RESULTS: Data from 202 consecutive patients from nine university hospitals were collected, but only data from 160 were analyzed (79.2 %). Most of the participants (70 %) were women with a mean age of 50 years (SD 1.2 years). The most frequent cancer site was breast (44 %) followed by lung (16 %) and 76.3 % were receiving highly emetogenous chemotherapy. Despite the use of antiemetic prophylaxis, patients experienced significant nausea and vomiting during 31 % (3.2 % during acute, 15.0 % during delayed phase, and 13.2 % during both phases) and 45.1 % (5.1 % only during the acute phase, 23.5 % only during the delayed phase and 16.5 % during both phases) of the cycles, respectively, having 44.5 % (nausea) and 39.3 % (emesis) of the cycles an impact on patients' QoL. CONCLUSIONS: The results of the study confirm the detrimental effect of CINV on patients' QoL despite the use of antiemetic prophylaxis (5HT(3) receptor antagonist, steroids, and dopamine receptor antagonists). It is mandatory to intensify the detection of CINV in order to improve the management of these important, albeit frequent, side effects of cancer treatments.

Phase II trial with letrozole to maximum response as primary systemic therapy in postmenopausal patients with ER/PgR[+] operable breast cancer

PURPOSE: Letrozole is superior to tamoxifen in terms of response and breast preservation rates as primary systemic therapy (PST) in postmenopausal women with ER-positive early breast cancer. However, the optimum duration of endocrine PST remains uncertain. METHODS: A phase 2 multicentre, open-label trial was conducted to evaluate the efficacy of letrozole over a preoperative period of 4 months to 1 year. Seventy postmenopausal patients (over 65 years) were recruited in four centers. The primary endpoint was to establish the optimal duration of treatment defined as the time required to attain the maximum response by clinical palpation. RESULTS: The median age of the group was 79 years (66-91) and the median tumour size 35 mm (range 25-100 mm). No severe adverse events were reported. Fifty-six patients were evaluable for the primary objective. A total of 43 patients (76.8%) achieved an objective response; 29 (51.8%) being partial and 14 (25.0%) complete. The median time to objective response was 3.9 months (95% CI, 3.3-4.5) and the median time to maximum response was 4.2 months (95% CI, 4.0-4.5), although 20 (37.1%) patients achieved the maximal response within 6-12 months. CONCLUSIONS: Letrozole shows a high activity and excellent tolerability as neoadjuvant therapy in elderly patients with endocrine-dependent breast cancer. Four to six months of letrozole as PST is an optimum duration with modest benefits thereafter (AU)

Sequential taxane and anthracycline-containing neoadjuvant regimens: the sequential order impact.

BACKGROUND: One can consider as a standard neoadjuvant treatment for breast cancer, the sequence of 4 cycles of anthracycline-based chemotherapy followed by 4 cycles of docetaxel. Based on the belief that the sequence order between anthracycline and taxane might be of interest, this study assessed the impact of the sequence order. METHODS: One hundred and twenty three patients with breast cancer were treated with neoadjuvant chemotherapy in 5 oncologic centers between 2003 and 2007. This study compared 65 patients treated with 4 cycles of docetaxel followed by 4 cycles of anthracycline-based chemotherapy (cohort T), versus another cohort of 58 patients treated with 4 cycles of anthracycline-based chemotherapy followed by 4 cycles of docetaxel (cohort A). RESULTS: The overall dose intensity of docetaxel and clinical complete responses were significantly higher in cohort T. No statistically significant differences were observed in terms of conservative surgeries or histological responses. The sequence of chemotherapy did not significantly influence other treatment-related toxicities. Mild neurotoxicity was higher in patients treated in cohort T. Anemias (≥Grade 1) were higher in cohort A (52% versus 81%; p = 0.0008). CONCLUSION: The present study failed to identify an impact of the sequence of taxane administration on the efficacy. Nevertheless, starting neoadjuvant chemotherapy by taxane reduces the occurrence of anemia. These findings might allow a selection of the sequence order based on the toxicity profile.

Disnea y tos persistente como primera manifestación de la recaída a distancia / Dyspnea and persistent cough as first signs of distant recurrence disease

La incidencia de metástasis endobronquiales secundarias a tumores sólidos es baja. Los tumores primarios que con más frecuencia producen metástasis endobronquiales son la mama, el colon y los tumores renales. Normalmente se presentan como una manifestación tardía de la enfermedad con un pronóstico malo y por su forma inespecífica de presentación precisan diagnóstico diferencial con los tumores pulmonares primarios (AU)

Endobronchial metastases secondary to extrapulmonary solid malignant tumours are rare. The most frequent primary tumours associated with endobronchial involvement are breast, colon and renal cell carcinoma. Endobronchial metastases usually appear later with a poorer prognosis and require differential diagnosis from a primary lung cancer (AU)

Efficacy of zoledronic acid in postmenopausal women with early breast cancer receiving adjuvant letrozole: 36-month results of the ZO-FAST Study.

BACKGROUND: Aromatase inhibitors (AIs) are accepted as adjuvant therapy for postmenopausal women (PMW) with hormone-responsive early breast cancer (EBC) with superior efficacy to tamoxifen. However, increased bone loss is associated with AIs. PATIENTS AND METHODS: PMW with EBC receiving letrozole (2.5 mg/day for 5 years) were randomly assigned to immediate zoledronic acid (ZOL; 4 mg every 6 months) or delayed ZOL (initiated only for fracture or high risk thereof). RESULTS: Patients (N = 1065) had a median age of 58 years; 54% had received prior adjuvant chemotherapy. At 36 months, mean change in L2-L4 bone mineral density (BMD) was +4.39% for immediate versus -4.9% for delayed ZOL (P < 0.0001). Between-group differences were 5.27% at 12 months, 7.94% at 24 months, and 9.29% at 36 months (P < 0.0001 for all). At 36 months, the immediate-ZOL group had a significant 41% relative risk reduction for disease-free survival (DFS) events (P = 0.0314). Adverse events are consistent with the known safety profiles of the study drugs. CONCLUSIONS: At 36 months, immediate ZOL was more effective in preserving BMD during letrozole therapy. Immediate versus delayed ZOL led to significantly improved DFS. Benefits are observed in the context of a favorable, well-established safety profile for letrozole and ZOL.

Actualidades del “San Antonio Breast Cancer Symposium 2006” / No disponible

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Biweekly gemcitabine plus vinorelbine in first-line metastatic breast cancer: efficacy and correlation with HER2 extracellular domain.

Purpose. To assess the toxicity and efficacy of biweekly gemcitabine plus vinorelbine in first-line advanced breast cancer, and to establish whether circulating HER2 ECD levels correlate with the efficacy of the combination. Patients and methods. 52 patients were treated with gemcitabine 2500 mg/m(2) plus vinorelbine 30 mg/m(2), both on day 1 of 14-day cycles, for a maximum of 10 cycles. Baseline serum levels of HER2 ECD were assessed with an ELISA. Results. All patients were evaluable for toxicity, and 50 for efficacy. Overall toxicity was moderate. Grade 3 neutropenia occurred in 35% of patients and grade 4 in 19%. Other grade 3 toxicities were observed in less than 6%. There was one episode of febrile neutropenia, and one death after cycle three. Overall response rate was 52% (95% CI: 38% to 66%), with 2 patients achieving a CR (4%). Response rate did not correlate with HER2 ECD, with 50% of HER2 ECD positive patients responding, vs 48.5% of the HER2 ECD negative. Median overall survival was 24.6 months. Conclusion. Gemcitabine plus vinorelbine, given as an every-two-week schedule, is an active regimen in advanced breast carcinoma. This combination can be an option when anthracyclines and taxanes are not preferred. HER2 ECD has no predictive value in this non-taxane combination.