46 research outputs found
Time to first tumor progression as outcome predictor of a second trasuzumab-based therapy beyond progression in HER-2 positive metastatic breast cancer
No full textIn a previous analysis performed on a cohort of 37 HER-2 positive metastatic breast cancer (MBC) patients treated with trastuzumab beyond progression, we found that a second trastuzumab-based therapy is associated with a considerable response rate and preserved time to progression as compared with a first trastuzumab-based therapy. In the present study, we extended the analysis to a total of 69 patients treated in four different italian Institutions, also trying to identify clinical predictors of sensitivity to a second trastuzumab-based therapy beyond progression. Efficacy results on the overall population confirmed that a second trastuzumab-based therapy beyond progression is an active regimen (27.5% of responses and 6.5 months of time to progression, respectively). Median time to progression to the first trastuzumab therapy (TTP1) identified two groups of patients with different sensitivity to trastuzumab beyond progression (group A, TTP1 >or= 8 months and group B, TTP1 < 8 months) in terms of time to second progression and post-progression survival (group A versus group B showed respectively a time to second progression of 7.6 versus 4.7 months, p = 0.05, and a post-progression survival of 31.7 months versus 21.8 months, p = 0.04). In the multivariate analysis, only TTP1 was a predictor of time to second progression and post-progression survival. Despite the recent approval of lapatinib plus capecitabine for trastuzumab-progressing patients, it is still reasonable to offer trastuzumab beyond progression to HER-2 positive MBC patients, because these data confirm the potential utility of such a conduct. In the clinic, time to first tumor progression may represent a useful tool to identify patients who are more likely to benefit from trastuzumab beyond progression
Predictive factors of response to neoadjuvant chemotherapy (NAT) in triple negative breast (TNBC) cancer patients: A restrospective multicenter observational study.
No full textBackground: This is a multicenter observational study with the aim to evaluate predictive factors of response to NAT in TNBC pts. Methods: 196 TNBC pts treated with NAT were enrolled from 7 Italian cancer centres and retrospectively evaluated for % of pCR, ki67 pre and postNAT and treatment duration. Pts receiving NAT regimens were divided in 2 groups: longer (TAC and anthra-taxane sequences) and shorter (35%).OS and PFS were calculated by the Kaplan-Meier product-limit method. Log-rank and Tarone-Ware tests were used to assess differences between groups. A multivariate logistic regression model was developed using stepwise regression (forward selection) to compare the predictive power of different factors. Results: Pts' median age was 47 yrs (25-77), cT1-T2 62%and cT3-cT4 38%, 79% of pts had clinical axillary disease, 41% of pts received longer NAT and 59% shorter. PreNAT ki67 levels were: LL 20%, IL 12% and HL 68%. PostNAT Ki-67: LL 22%, IL 6%, and HL 42%, and 52 pts (26.5%) achieved pCR (95%CI 20-33). In the group of pts that received longer NAT, pCR was significantly more frequent compared to the group that received shorter NAT (38% vs 19% p = 0.005). Moreover pCR was more frequent in pts HL of Ki-67 (34%) compared to those with LL/IL (20%)(p = 0.05). In multivariate analysis HL of preNAT Ki-67 (OR 1.2 CI 95%1-1.3, p = 0.02) and longer duration of NAT response (OR 2.1 CI95% 1-4.3, p = 0.04) were significant predictive factors for. Conversely, cT and cN didn’t appear predictive. At a median follow-up of 42 months (2-190) overall PFS at 3yrs was 65% and 5yrs OS 76%. Pts with pCR had higher DFS and OS than pts with NopCR. DFS and OS gradually worsened with increasing postNAT Ki-67 level. Conclusions: Our analysis suggests that in TNBC treated with pre-NAT high ki67 levels and “adeguate” chemotherapy regimen are predictive factors of response and that post-NAT high ki67 levels and nopCR are negative predictors of survival. Data collection is ongoing and update results will be presented.
DFS 3yrs (%) OS 5yrs (%)
Ki67 HL >35% 56.3 62.2
pCR 92.9 92.9
No pCR 56.4 70.
Long-Term Outcomes With Pharmacological Ovarian Suppression During Chemotherapy in Premenopausal Early Breast Cancer Patients
No full textAlthough use of gonadotropin-releasing hormone agonist (GnRHa) during chemotherapy is an established strategy to protect ovarian function in premenopausal breast cancer patients, no long-term safety data are available, raising some concerns in women with hormone receptor-positive disease. There are controversial data on its fertility preservation potential
EFFECT: a randomized phase II study of efficacy and impact on function of two doses of nab-paclitaxel as first-line treatment in older women with advanced breast cancer
No full textLimited data are available regarding the use of nab-paclitaxel in older patients with breast cancer. A weekly schedule is recommended, but there is a paucity of evidence regarding the optimal dose. We evaluated the efficacy of two different doses of weekly nab-paclitaxel, with a specific focus on their corresponding impact on patient function, in order to address the lack of data specifically relating to the older population
Trastuzumab plus lapatinib or chemotherapy in patients with HER2-overexpressed advanced breast cancer: a randomized, phase II trial (GIM12-TYPHER)
No full textBackground Trastuzumab combined with chemotherapy is a standard treatment for human epidermal growth factor receptor 2 (HER2)-positive advanced breast cancer in later lines. Lapatinib and trastuzumab have also demonstrated efficacy. This study assessed the efficacy, toxicity, and quality of life (QoL) of trastuzumab plus lapatinib (with endocrine therapy for hormone receptor-positive cases) versus trastuzumab with physician-selected chemotherapy in patients previously treated with at least 2 anti-HER2 regimens. Methods In this open-label, multicenter phase II trial, 59 patients were randomized 1:1 to receive either trastuzumab and lapatinib (arm A) or trastuzumab with chemotherapy (arm B). The primary endpoint was clinical benefit rate (CBR), defined as confirmed complete response, partial response, or stable disease for ≥24 weeks. Secondary endpoints included overall survival (OS), progression-free survival (PFS), overall response rate (ORR), QoL, and safety. Results With a median follow-up of 57.5 months, the CBR was 20.7% in arm A and 26.7% in arm B (P = .76). The ORR was 13.8% versus 20.0% (P = .73), and median PFS was 3.6 months in arm A versus 6.1 months in arm B (HR 0.63; P = .08). Median OS was 29.9 versus 31.1 months (HR 1.07; P = .82). Adverse events occurred in 86.2% (arm A) and 66.7% (arm B) of patients, with grade 3-4 events in 24.1% and 13.3%, respectively. QoL favored arm A (P = .03). Due to early study closure and limited sample size, all results should be considered exploratory and not powered to assess definitive treatment effects. Conclusions While efficacy differences were not significant, trastuzumab with lapatinib showed better QoL despite higher adverse event rates, suggesting it may be a viable chemotherapy-free option for pretreated HER2-positive advanced breast cancer. EudraCT trial registration number 2013-005044-2
Symptom improvement as prognostic factor for survival in cancer patients undergoing palliative care: a pilot study
No full textBody mass index in HER2-negative metastatic breast cancer treated with first-line paclitaxel and bevacizumab
No full textThe evidence emerged from the TOURANDOT trial encourages evaluating the role of anthropometric determinants on treatment outcomes in HER2-negative metastatic breast cancer patients treated with bevacizumab-including regimens. We thus analyzed data from a subgroup of these patients from a larger cohort previously assessed for treatment outcomes. Patients were included in the present analysis if body mass index values had been recorded at baseline. Clinical benefit rates, progression free survival and overall survival were assessed for the overall study population and subgroups defined upon molecular subtype. One hundred ninety six patients were included (N:196). Body mass index showed no impact on clinical benefit rates in the overall study sample and in the luminal cancer subset (p = 0.12 and p = 0.79, respectively), but did so in the triple negative subgroup, with higher rates in patients with body mass index â¥25 (p = 0.03). In the overall study sample, body mass index did no impact progression free or overall survival (p = 0.33 and p = 0.67, respectively). Conversely, in triple negative patients, progression free survival was significantly longer with body mass index â¥25 (6 vs 14 months, p = 0.04). In this subset, overall survival was more favorable (25 vs 19 months, p = 0.02). The impact of the molecular subtype was confirmed in multivariate models including the length of progression free survival, and number of metastatic sites (p < 0.0001). Further studies are warranted to confirm our findings in more adequately sized, ad hoc, prospective studies
Neoadjuvant chemotherapy in triple-negative breast cancer: A multicentric retrospective observational study in real-life setting
No full textWe aimed to assess the efficacy of neoadjuvant chemotherapy (NACT) in a cohort of 213 triple-negative breast cancer (TNBC) patients treated in real-world practice at eight Italian cancer centers. We computed descriptive statistics for all the variable of interest. Factors testing significant in univariate analysis were included in multivariate models. Survival data were compared by Kaplan-Meier curves and log-rank test. The median follow-up was 45 months. We observed 60 (28.2%) pathological complete response (pCR). The sequential anthracyclines-taxanes-based regimens produced the highest rate of pCR (42.6%), followed by concomitant anthracycline-taxane (24.2%), and other regimens (15.6%) (p = 0.008). When analyzing the role of baseline Ki-67, a 50% cut-off was the optimal threshold value for pCR prediction (p = 0.0005). The 5-year disease-free survival (DFS) was 57.3% and the 5-year overall survival (OS) was 70.8%. In patients not achieving pCR, the optimal Ki-67 variation between biopsy and surgical specimen with prognostic relevance on long-term outcomes was 13% (p = 0.04). Patients with a Ki-67 reduction (rKi-67)6 cycles compared with their counterparts, p = 0.02). In multivariate analysis, node status, grading, and bio-pathological treatment response (including pCR and rKi-67) impacted DFS and OS. Our results confirmed the advantage conferred by more than 6 cycles of a sequential antracycline-taxane-based NACT. Higher baseline Ki-67 values shows greater predictive significance on pathogical response, while the rKi-67 plays a prognostic role on long-term outcomes
A Real-World Multicentre Retrospective Study of Paclitaxel-Bevacizumab and Maintenance Therapy as First-Line for HER2-Negative Metastatic Breast Cancer
No full textBevacizumab in combination with taxanes in HER2-negative metastatic breast cancer (MBC) patients has shown improved progression-free survival (PFS), despite the lack of clear overall survival (OS) benefit. We performed a retrospective analysis to evaluate the impact of paclitaxel-bevacizumab and of maintenance therapy with bevacizumab (BM) and endocrine therapy (ET) in the real-world practice. We identified 314 HER2-negative MBC patients treated in 12 cancer centers. Overall, the median PFS and OS were 14 and 40 months, respectively. Among the 254 patients potentially eligible for BM, 183 received BM after paclitaxel discontinuation until progression/toxicity. PFS and OS were improved in patients who had received BM in comparison with those potentially eligible but who did not receive BM (P< 0.0001 and P = 0.001, respectively). Results were confirmed when adjusting for propensity score. Among the 216 hormone-receptor positive patients eligible for BM, a more favorable PFS and OS were observed when maintenance ET was administered (P < 0.0001). Multivariate analysis showed that PS, BM, number of disease sites and maintenance ET were related to PFS, while response and maintenance ET were related to OS. In hormone-receptor positive patients, BM produced a significant PFS and a trend towards OS benefit only in absence of maintenance ET (P = 0.0007 and P = 0.06, respectively). In the triple-negative subgroup, we observed a trend towards a better OS for patients who received BM (P = 0.06), without differences in PFS (P = 0.21). Our results confirmed the efficacy of first-line paclitaxel-bevacizumab in real-world practice; both BM and maintenance ET significantly improved PFS and OS compared to no maintenance therapies. J. Cell. Physiol. 232: 1571–1578, 2017. © 2016 Wiley Periodicals, Inc
