e13068 Background: Second-line treatment for HR+/HER2- MBC is evolving, requiring integration of new treatment strategies such as CDK4/6i BP novel targeted agents in association to endocrine therapy, and antibody-drug conjugates (ADCs). The aim of this study is to explore ctDNA biomarkers impacting second progression free survival (PFS2) in patients (pts) treated with CDK4/6i BP. Methods: This study used the nationwide (US-based) deidentified Flatiron Health-Foundation Medicine clinicogenomic database (FH-FMI CGDB), comprising data originated from ~280 US cancer clinics (~800 sites of care). In this study a synthetic control arm (SCA) was constructed from the FH-FMI CGDB (n = 145) as comparator for a prospective multi-institutional cohort of patients treated with CDK4/6i BP (n = 65). Pts in both subgroups were profiled through ctDNA using the FoundationOne Liquid NGS panel. A 1:1 Propensity Score Matching (PSM) was applied to balance covariates, including age at diagnosis, ECOG status, bone-only or lymph node metastatic involvement, and PFS1 CDK4/6i treatment duration. Pathogenic alterations with a > 10% prevalence were analyzed individually and according to oncogenic pathways (Sanchez-Vega et al., Cell , 2018). The prognostic impact of single nucleotide and copy number variations (SNVs and CNVs) was assessed in terms of PFS2, defined as the time from second-line treatment initiation to progression or death. Results: A total of 130 pts were analyzed after PSM. Liver was the most frequent metastatic site, observed in 30.8% of the fulvestrant + palbociclib BP cohort (F+P) and 36.9% of the FH-FMI CGDB cohort (fulvestrant monotherapy; F). ESR1 was the most frequently altered gene (38%), followed by BRCA2 (32%), TP53 (29%), ATM (28%), and PIK3CA (28%). PFS2 was comparable between the two cohorts, with no significant difference (Hazard Ratio (HR) comparing F+P vs F HR = 1.36, P = 0.1141). In the overall population, cell cycle CNV significantly impacted PFS2 (HR: 2.03, P = 0.005), while in the F+P cohort, CNV in the P53 pathway had a significant impact (HR: 5.6, P = 0.024) with MDM2 CNV as main contributor. Multivariable analysis confirmed that in the F cohort, SNVs in the RTK/RAS pathway and CNVs in the cell cycle pathway significantly impacted PFS2 (HR: 2.31, P = 0.014 and HR: 2.16, P = 0.016, respectively). At the single-gene level, CNVs in the chromosome 11q13.3 region (i.e. CCND1 , FGF19 , FGF3 , and FGF4 ) were associated with PFS2 in the F group but not in the F+P group. Conclusions: The SCA developed in this analysis confirmed findings from the PACE prospective trial and highlighted a differential prognostic impact of ctDNA features across treatment subgroups. These results provide valuable insights for personalized treatment algorithms and could guide therapeutic decisions and future clinical trial design.

1047 Background: New targeted therapies, including novel endocrine agents and antibody drug conjugates, are revolutionizing the treatment of HR+/HER2- metastatic breast cancer (MBC). However, questions surrounding primary and secondary endocrine resistance (R1 and R2, respectively) still hinder the development of personalized treatment strategies. This study aimed to investigate R1 by leveraging liquid biopsy in a hybrid real-world and clinical trial dataset. Methods: This study used the nationwide (US-based) deidentified Flatiron Health-Foundation Medicine MBC clinicogenomic database (FH-FMI CGDB), comprising data originated from ~280 US cancer clinics (~800 sites of care), and analyzed a cohort of 855 patients (pts) profiled through the FoundationOne Liquid CDx NGS panel, combining it with the first 65 pts enrolled in the GIM-24-PalboBP study (NCT04318223). R1 was defined as 1-line PFS of < 6 months. A 1:3 Propensity Score Matching was applied to balance key factors (i.e. age, ECOG performance status, visceral, lymph node, multiple metastasis, type of CDK6/4i). Pathogenic alterations with a > 10% prevalence were tested singularly and according to oncogenic pathways based on Sanchez-Vega F et al, Cell. 2018. Associations between ctDNA alterations, R1, and R2 were assessed using logistic regression, while prognosis was evaluated through Cox regression. Results: A set of 528 pts (respectively 132 and 396 for R1 and R2) was selected from the original cohort of 855 pts. Top detected alterations were PIK3CA SNV (46%), TP53 SNV (33%) and ESR1 SNV (24%). R1 was associated with TP53 SNV (OR = 2.30, P < 0.001), CCND1, FGF19, FGF3 and FGF4 CNVs (respectively OR = 1.75, P = 0.018; OR = 1.62, P = 0.044; OR = 1.80, P = 0.015; OR = 1.73, P = 0.024). On the other hand, ESR1 SNV was associated with R2 (OR = 0.47, P = 0.005). CCND1, FGF19, FGF3 and FGF4 CNVs were significantly co-occurring (P < 0.001) and located in the chromosome (chr)11q13.3 region. In multivariable analysis, TP53 SNV, ESR1 SNV and chr11q13.3 CNV maintained their association with R1 (respectively OR = 2.22, P < 0.001; OR = 0.47, P = 0.006 and OR = 1.94, P = 0.006). Pathway analysis was consistent, showing a significant association between R1 and SNVs in the P53 and in the ER pathways (respectively OR = 1.92, P = 0.002; OR = 0.58, P = 0.024) and CNVs in the cell cycle pathway (OR = 2.18, P = 0.001). No differences were observed for 2-line (PFS2) across R1 and R2 (median PFS2 8.89 vs 8.03 months P = 0.589). Chemotherapy was prevalent in the R1 group (35% vs 15%). Within pts receiving 2-line endocrine therapy, TP53 SNV was the only prognostic factor in R1 (HR = 2.02, P = 0.008), while SNVs in TP53 and ESR1 had an impact on PFS2 in R2 (respectively HR = 1.50, P = 0.003 and HR = 1.45, P = 0.008). Conclusions: This study confirms TP53 and ESR1 as key factors for R1 and R2, respectively, with ESR1 showing a prognostic impact on PFS2 in R2 only. Additionally, chr11q13.3 emerges as a new candidate region for R1. These results provide critical data for both decision making and 2-line clinical trial design.

Background/Objectives: HER2-positive breast cancer (HER2+BC) is an aggressive subtype, with neoadjuvant treatment (NAT) aiming to achieve a pathological complete response (pCR) to improve long-term outcomes. Trastuzumab emtansine (T-DM1) has been established as the standard of care in the adjuvant setting for HER2+BC patients who do not obtain pCR. The ATD study aimed to evaluate the real-world tolerability of T-DM1 in this setting. The secondary objective was to assess the effectiveness. Methods: This was a multicenter, retrospective study across 24 Italian oncology centers, including 410 patients with HER2+BC treated with adjuvant T-DM1 following a lack of pCR after NAT. Patient characteristics, NAT regimens, and surgical outcomes were recorded. Tolerability was assessed by documenting adverse events (AEs) according to the CTCAE (v5.0). Preliminary effectiveness was evaluated in terms of relapse-free survival (RFS) and overall survival (OS). Results: Overall, 228 patients (55.6%) experienced at least one AE related to T-DM1, with 4.9% experiencing grade 3 or higher AEs. The most common AEs were hepatotoxicity (18.5%) and thrombocytopenia (17.6%). T-DM1 was discontinued in 10.0% of patients due to toxicity. After a median follow-up of 25 months, 31 relapse events (7.6%) and 22 deaths (5.4%) were reported. The preliminary incidence of RFS and OS events was similar between patients who completed the T-DM1 course and those who discontinued it early. Conclusions: T-DM1 demonstrated a manageable safety profile, and the adverse events were consistent with those reported in randomized trials. The data are not yet sufficient to allow for a formal analysis of RFS and OS, and long-term follow-up is required.

PurposeClinical trials have shown a significant increase in pathologic complete response (pCR) with the addition of pertuzumab to neoadjuvant chemotherapy for patients with early-stage HER-2 positive breast cancer. To date, limited studies have examined comparative outcomes of neoadjuvant pertuzumab in real-world setting. The Neopearl study aimed to assess comparative real-life efficacy and safety of neoadjuvant pertuzumab for these patients.MethodsWe conducted a nationwide retrospective analysis involving 17 oncology facilities with a certified multidisciplinary breast cancer treatment committee. We identified patients with HER-2 positive stage II-III breast cancer treated with neoadjuvant chemotherapy based on trastuzumab and taxanes with or without pertuzumab. All patients underwent breast surgery and received a comprehensive cardiologic evaluation at baseline and after neoadjuvant treatment. Patients who received the combination of pertuzumab, trastuzumab, and chemotherapy constituted case cohort (PTCT), whereas those treated with trastuzumab and chemotherapy accounted for control cohort (TCT). The pCR rate and 5-year event free survival (EFS) were the primary outcomes. Secondary end-points were rates of conversion from planned modified radical mastectomy (MRM) to breast conservation surgery (BCS) and cardiotoxicities.ResultsFrom March 2014 to April 2021, we included 271 patients, 134 (49%) and 137 (51%) in TCT and PTCT cohort, respectively. Positive axillary lymph nodes and stage III were more frequent in PTCT cohort. The pCR rate was significantly increased in patients who received pertuzumab (49% vs 62%; OR 1.74, 95%CI 1.04-2.89) and with HER-2 enriched subtypes (16% vs 85%; OR 2.94, 95%CI 1.60-5.41). After a median follow-up of 5 years, the 5-year EFS was significantly prolonged only in patients treated with pertuzumab (81% vs 93%; HR 2.22, 95%CI 1.03-4.79). The same analysis performed on propensity score matched population showed concordant results. On univariate analysis, only patients with positive lymph nodes were found to benefit from pertuzumab for both pCR and 5-year EFS. The rates of conversion from MRM to BCS and cardiologic toxicities did not differ between the cohorts.ConclusionOur findings support previous data on improved outcomes with the addition of pertuzumab to trastuzumab-based neoadjuvant chemotherapy. This benefit seems to be more significant in patients with clinically positive lymph nodes.

Trastuzumab (T) and chemotherapy (CT) is a standard treatment in patients (pts) with HER2-positive (+) advanced breast cancer (ABC) at later lines of therapy. Lapatinib (L) and T have proven to be active in the same setting. The present study evaluated the efficacy, toxicity and quality of life (QoL) of T+L versus T + physician's choice CT in pts with HER2+ ABC pretreated with at least two lines of anti-HER2 treatment. In this open-label, multicenter, phase II trial, pts were randomly assigned 1:1 to receive either T+L with endocrine therapy at the physician's discretion in case of hormone receptor positive ABC (arm A) or T+CT (arm B). The primary endpoint was the clinical benefit rate (CBR) and the secondary endpoints included overall survival (OS), progression-free survival (PFS), quality of life (QoL), and safety. Between 2015 and 2020, 59 pts were randomized and evaluated for the present analyses. After a median (m) follow-up of 57.5 months (mo), the CBR was 20.7% (95% CI 9.4-39.3) vs 26.7% (95% CI 13.1-44.9; P= 0.76), the mOS was 29.9 mo (95% CI 19.6-NE) vs 31.1 mo (95% CI 26.1-NE; hazard ratio [HR] 1.07, 95% CI 0.57-2.0; P=0.82) and mPFS was 3.6 mo (95% CI 3.0-5.3) vs 6.1 mo (95% CI 4.0-14.3; HR 0.63, 95% CI 0.37-1.37; P=0.08) in arm A vs arm B, respectively. Any grade (G) adverse events (AEs) occurred in 86.2% and 66.7% of pts in arm A and B, respectively. The incidence of G3-4 AEs was 24.1% and 13.3% in arm A and B, respectively. The impact on QoL significantly favored arm A (P=0.03).Table: 209PAEsOverall (N=59)Arm A (N=29)Arm B (N=30)Patients with at least one AE45 (76.3)25 (86.2)20 (66.7)Diarrhea14 (23.7)11 (37.9)3 (10)Fatigue13 (22)7 (24.1)6 (20)Abdominal pain7 (11.9)3 (10.3)4 (13.3)Anemia7 (11.9)4 (13.8)3 (10)Neutropenia5 (8.5)0 (0)5 (16.7)Nausea5 (8.5)3 (10.3)2 (6.7)Thrombocytopenia5 (8.5)4 (13.8)1 (3.3)Paresthesia4 (6.8)0 (0)4 (13.3)Fever3 (5.1)3 (10.3)0 (0)Skin disorders3 (5.1)3 (10.3)0 (0) Open table in a new tab No difference in efficacy was observed between T+L and T+CT. QoL deterioration was less frequent in pts in T+L arm though a higher number of any AEs was observed in these patients compared with those who received T+CT. Overall, the chemotherapy-free combination of T+L may be a valid therapeutic option for pretreated pts with HER2+ ABC.

Sex might influence prognosis in patients affected by colorectal cancer. We retrospectively studied a cohort of patients affected by metastatic colon cancer (mCC) stratified by sex and primary tumor location. RAS mutational status was also included in the analysis. Overall, 616 patients met the eligibility criteria, 261 women and 355 men. Neither gender, nor RAS mutational status influenced overall survival (OS) in the entire population. As expected, patients with right-sided colon cancer (RCC) had a significant shorter OS compared to those with left-sided colon cancer (LCC) (21.3 vs 33.1 months, p= 0.002). When the analysis was performed stratifying for gender, RCC retained worse prognosis among men (OS 20.5 vs 33.9 months, p= 0.008), but not among women (p= 0.132). Similarly, the presence of RAS mutations had no prognostic effect in women, but was significantly associate with shorter survival in men (OS 29.5 vs 33.7 months, p= 0.046). In addition, when comparing clinical outcome of women or men according to sidedness and RAS mutational status, RCC was associated with dismal prognosis only in men with RAS mutated tumor (OS 17.2 vs 32.3 months, p= 0.008). Our study highlights the importance of gender in the outcome of patients with mCC.

GIM 13-AMBRA is a longitudinal cohort study aimed at describing therapeutic strategies and the relative outcome parameters in 939 HER2-ve MBC patients. Taxanes–based regimens, or taxanes + targeted agents, mainly Bevacizumab, were the preferred first choice in both Luminal (30.2%) and TNBC (33.3%) patients. The median PFS1 was 12.5 months (95% CI 16.79–19.64), without any significant difference according to subtypes, while the median Time to first Treatment Change (TTC1) was significantly lower in TNBC patients (7.7 months—95% CI 5.7–9.2) in comparison to Luminal A (13.2 months, 95% CI 11.7–15.1) and Luminal B patients (11.8 months, 95% CI 10.3–12.8). PFS2 was significantly shorter in TNBC patients (5.5 months, 95% CI 4.3–6.5 vs. Luminal A—9.4, 95% CI 8.1–10.7, and Luminal B—7.7 95% CI 6.8–8.2, F-Ratio 4.30, p = 0.014). TTC2 was significantly lower in patients with TNBC than in those with the other two subtypes. The median OS1 was 35.2 months (95% CI 30.8–37.4) for Luminal A patients, which was significantly higher than that for both Luminal B (28.9 months, 95% CI 26.2–31.2) and TNBC (18.5 months, 95% CI 16–20.1, F-ratio 7.44, p = 0.0006). The GIM 13—AMBRA study is one of the largest collections ever published in Italy and provides useful results in terms of time outcomes for first, second, and further lines of treatment in HER2- MBC patients.

Background In triple negative breast cancer patients treated with neoadjuvant chemotherapy, residual disease at surgery is the most relevant unfavorable prognostic factor. Current guidelines consider the use of adjuvant capecitabine, based on the results of the randomized CREATE-X study, carried out in Asian patients and including a small subset of triple negative tumors. Thus far, evidence on Caucasian patients is limited, and no real-world data are available. Methods We carried out a multicenter, observational study, involving 44 oncologic centres. Triple negative breast cancer patients with residual disease, treated with adjuvant capecitabine from January 2017 through June 2021, were recruited. We primarily focused on treatment tolerability, with toxicity being reported as potential cause of treatment discontinuation. Secondarily, we assessed effectiveness in the overall study population and in a subset having a minimum follow-up of 2 years. Results Overall, 270 patients were retrospectively identified. The 50.4% of the patients had residual node positive disease, 7.8% and 81.9% had large or G3 residual tumor, respectively, and 80.4% a Ki-67 >20%. Toxicity-related treatment discontinuation was observed only in 10.4% of the patients. In the whole population, at a median follow-up of 15 months, 2-year disease-free survival was 62%, 2 and 3-year overall survival 84.0% and 76.2%, respectively. In 129 patients with a median follow-up of 25 months, 2-year disease-free survival was 43.4%, 2 and 3-year overall survival 78.0% and 70.8%, respectively. Six or more cycles of capecitabine were associated with more favourable outcomes compared with less than six cycles. Conclusion The CaRe study shows an unexpectedly good tolerance of adjuvant capecitabine in a real-world setting, although effectiveness appears to be lower than that observed in the CREATE-X study. Methodological differences between the two studies impose significant limits to comparability concerning effectiveness, and strongly invite further research.

(1) Background: This study aims to assess the safety and efficacy of fractionated SRT (fSRT) and pertuzumab–trastuzumab (PT) in patients with breast cancer brain metastases (BCBM). (2) Methods: Patients with HER2+ BCBM who received FSRT from 2015 to 2019 were identified. Patients were included if they were treated with fSRT within 21 days of receiving PT. All lesions were treated with LINAC-based fSRT to a total dose of 27 Gy delivered in three consecutive fractions. All patients received concurrent PT. Patients were evaluated 4–6 weeks after SRS and subsequently every 2–3 months with MRI re-imaging (3) Results: A total of 49 patients with HER2+ brain metastases were identified. Of these patients, a total of 10 patients with 32 HER2+ BCBM were treated with concurrent SRT and PT and included in the analysis. No local progression was observed. Overall response rate was 68.7%. Only one patient developed asymptomatic radionecrosis. Median time to BM occurrence was 15.6 (range: 1–40.5 months). Distant intracranial failure occurred in 4/10 patients (40.0%). Overall BCBM median survival was 33.9 months (95%CI 24.1–43.6). Mean duration of PT treatment was 27.9 months (range: 10.1–53.7 months). (4) Conclusions: In our single institution experience, fSRT and PT showed to be a safe treatment for patients with BCBM with an adequate overall response rate.

Clinicopathological prognostic features have limited value to identify with precision newly diagnosed patients with hormone receptor (HR)-positive, HER2-negative breast cancer (BC), who would benefit from chemotherapy (CT) in addition to adjuvant hormonal therapy (HT). The 21-gene Oncotype DX Breast Recurrence Score ® (RS) assay has been demonstrated to predict CT benefit, hence supporting personalized decisions on adjuvant CT. The multicenter, prospective, observational study PONDx investigated the real-life use of RS ® results in Italy and its impact on treatment decisions. Physicians’ treatment recommendations (HT ± CT) were documented before and after availability of RS results, and changes in recommendations were determined. In the HR+ HER2− early BC population studied ( N = 1738), physicians recommended CT + HT in 49% of patients pre-RS. RS-guided treatment decisions resulted in 36% reduction of CT recommendations. PONDx confirms that RS results provide clinically relevant information for CT recommendation in early-stage BC, resulting in a reduction of more than a third of CT use.

In metastatic breast cancer (mBC), the change of human epidermal growth factor receptor 2 (HER2) status between primary and metastatic lesions is widely recognized, however clinical implications are unknown. Our study address the question if relevant differences exist between subjects who preserve the HER2 status and those who gain the HER2 positivity when relapsed. Data of patients affected by HER2-positive mBC, treated with pertuzumab and/or trastuzumab-emtansine (T-DM1) in a real-world setting at 45 Italian cancer centers were retrospectively collected and analyzed. From 2003 to 2017, 491 HER2‐positive mBC patients were included. Of these, 102 (20.7%) had been initially diagnosed as HER2-negative early BC. Estrogen and/or progesterone receptor were more expressed in patients with HER2-discordance compared to patients with HER2-concordant status ( p < 0.0001 and p = 0.006, respectively). HER2-discordant tumors were characterized also by a lower rate of brain metastases ( p = 0.01) and a longer disease free interval ( p < 0.0001). Median overall survival was longer, although not statistically significant, in the subgroup of patients with HER2-discordant cancer with respect to patients with HER2-concordant status (140 vs 78 months, p = 0.07). Our findings suggest that patients with HER2-positive mBC with discordant HER2 status in early BC may have different clinical, biological and prognostic behavior compared to HER2-concordant patients.

Introduction: Large and consistent evidence supports the use of eribulin mesylate in clinical practice in third or later line treatment of metastatic triple negative breast cancer (mTNBC). Conversely, there is paucity of data on eribulin efficacy in second line treatment. Methods: We investigated outcomes of 44 mTNBC patients treated from 2013 through 2019 with second line eribulin mesylate in a multicentre retrospective study involving 14 Italian oncologic centres. Results: Median age was 51 years, with 11.4% of these patients being metastatic at diagnosis. Median overall survival (OS) and progression free survival (PFS) from eribulin starting were 11.9 (95%CI: 8.4-15.5) and 3.5 months (95%CI: 1.7-5.3), respectively. We observed 8 (18.2%) partial responses and 10 (22.7%) patients had stable disease as best response. A longer PFS on previous first line treatment predicted a better OS (HR=0.87, 95%CI: 0.77-0.99, p= 0.038) and a longer PFS on eribulin treatment (HR=0.92, 95%CI: 0.85-0.98, p=0.018). Progression free survival to eribulin was also favorably influenced by prior adjuvant chemotherapy (HR=0.44, 95%CI: 0.22-0.88, p=0.02). Eribulin was generally well tolerated, with grade 3-4 adverse events being recorded in 15.9% of patients. Conclusions: The outcomes described for our cohort are consistent with those reported in the pivotal Study301 and subsequent observational studies. Further data from adequately-sized, ad hoc trials on eribulin use in second line for mTNBC are warranted to confirm our findings.

The GIM2 phase III trial demonstrated the benefit of dose-dense chemotherapy in node-positive early breast cancer (eBC). To better define the dose-dense effect in the hormone receptor-positive subgroup, we evaluated its benefit through a composite measure of recurrence risk. We conducted an ancillary analysis of the GIM2 trial evaluating the absolute treatment effect through a composite measure of recurrence risk (CPRS) in patients with hormone receptor-positive HER2-negative eBC. CPRS was estimated through Cox proportional hazards models applied to the different clinicopathological features. The treatment effect was compared to the values of CPRS by using the Sub-population Treatment Effect Pattern Plot (STEPP) process. The Disease-Free Survival (DFS)-oriented STEPP analysis showed distinct patterns of relative treatment effect with respect to CPRS. Overall, 5-year DFS differed across CPRS quartiles ranging from 95.2 to 66.4%. Each CPRS quartile was characterized by a different patients' composition, especially for age, lymph node involvement, tumor size, estrogen and progesterone receptor expression, and Ki-67. A number needed to treat of 154 and 6 was associated with the lowest and the highest CPRS quartile, respectively. Dose-dense adjuvant chemotherapy showed a consistent benefit in node-positive eBC patients with hormone receptor-positive HER2-negative disease, but its effect varied according to CPRS.

Hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer is the most common breast cancer subtype, and endocrine therapy (ET) remains its therapeutic backbone. Although anti-estrogen therapies are usually effective initially, approximately 50% of HR+ patients develop resistance to ET within their lifetime, ultimately leading to disease recurrence and limited clinical benefit. The recent addition of cyclin-dependent kinase 4 (CDK4) and CDK6 inhibitors (palbociclib, ribociclib, abemaciclib) to ET have remarkably improved the outcome of patients with HR+ advanced breast cancer (ABC) compared with anti-estrogens alone, by targeting the cell-cycle machinery and overcoming some aspects of endocrine resistance. However, which patients are the better candidates for these drugs, which are the main characteristics for a better selection of patients or if there are predictive biomarkers of response, is still unknown. In this review we reported the mechanism of action of CDK4/6 inhibitors as well as their potential mechanism of resistance, their implications in clinical practice and the forthcoming strategies to enhance their efficacy in improving survival and quality of life of patients affected with HR+, HER2−, ABC.

The novel coronavirus disease 2019 (COVID-19) pandemic has been an overwhelming challenge for worldwide health systems. Since the beginning of year 2020, COVID-19 has represented a potential harm for cancer patients and has often hindered oncology care. The Collegio Italiano dei Primari Oncologi Medici (CIPOMO) is an Italian association of head physicians in oncology departments, which promotes working and research activities in oncology on a national basis. During the second wave of COVID-19 pandemic, the CIPOMO promoted a national survey aiming to evaluate the impact of COVID-19 on oncologists' clinical activity and what changes have been made compared with the Italian situation during the first wave of the pandemic. Overall, 138 heads of medical oncology departments participated in this survey: 75 (54%) from the North, 24 (17%) from the Centre and 39 (28%) from the South of Italy and islands. This survey provides an overview of Italian oncologists facing the second wave of COVID-19 pandemic. The lesson learned during the first wave of COVID-19 pandemic has led to a better organisation of clinical activities, and regular testing among healthcare practitioners, with better chances to grant patients' protection. However, the lack of standardised informatic platforms results in serious challenges in replacing frontal visits, often making a concrete reduction of patients' hospital accesses unfeasible. Oncologists need to keep preserving the continuum of care of patients. Standardisation of safety measures, together with the implementation of informatic platforms, can significantly improve oncology pathways during this second wave of COVID-19 pandemic.

Background: We evaluated the efficacy and safety of the nontaxane microtubule dynamics inhibitor eribulin plus the humanized anti-VEGF monoclonal antibody bevacizumab in a novel second-line chemotherapy scheme in HER2-negative metastatic breast cancer (MBC) patients progressing after first-line paclitaxel and bevacizumab. Patients and methods: This is a multicenter, single-arm, Simon's two-stage, phase II study. The primary endpoint was the overall response rate, considered as the sum of partial and complete response based on the best overall response rate (BORR). The secondary endpoints were progression-free survival (PFS), overall survival (OS), and clinical benefit rate. Results: A total of 58 of the 61 patients enrolled in the study were evaluable for efficacy. The BORR was 24.6% (95% CI 14.5-37.3). The clinical benefit rate was 32.8% (95% CI 21.3-46.0). The median PFS was 6.2 months (95% CI 4.0-7.8), and median OS was 14.8 months (95% CI 12.6-22.8). Overall, adverse events (AEs) were clinically manageable and the most common AEs were fatigue, paresthesia, and neutropenia. Quality of life was well preserved in most patients. Conclusions: The results of this study suggest that second-line therapy with bevacizumab in combination with eribulin has a meaningful clinical activity and may represent a potential therapeutic option for patients with HER2-negative MBC.

BACKGROUND:The evolution of therapeutic landscape of human epidermal growth factor receptor-2 (HER2)-positive breast cancer (BC) has led to an unprecedented outcome improvement, even if the optimal sequence strategy is still debated. To address this issue and to provide a picture of the advancement of anti-HER2 treatments, we performed a large, multicenter, retrospective study of HER2-positive BC patients.METHODS:The observational PANHER study included 1,328 HER2-positive advanced BC patients treated with HER2 blocking agents since June 2000 throughout July 2020. Endpoints of efficacy were progression-free survival (PFS) and overall survival (OS).RESULTS:Patients who received a first-line pertuzumab-based regimen showed better PFS (p < 0.0001) and OS (p = 0.004) than those receiving other treatments. Median PFS and mOS from second-line starting were 8 and 28 months, without significant differences among various regimens. Pertuzumab-pretreated patients showed a mPFS and a mOS from second-line starting not significantly affected by type of second line, that is, T-DM1 or lapatinib/capecitabine (p = 0.80 and p = 0.45, respectively). Conversely, pertuzumab-naïve patients receiving second-line T-DM1 showed a significantly higher mPFS compared with that of patients treated with lapatinib/capecitabine (p = 0.004). Median OS from metastatic disease diagnosis was higher in patients treated with trastuzumab-based first line followed by second-line T-DM1 in comparison to pertuzumab-based first-line and second-line T-DM1 (p = 0.003), although these data might be partially influenced by more favorable prognostic characteristics of patients in the pre-pertuzumab era. No significant differences emerged when comparing patients treated with 'old' or 'new' drugs (p = 0.43), even though differences in the length of the follow-up between the two cohorts should be taken into account.CONCLUSION:Our results confirmed a relevant impact of first-line pertuzumab-based treatment and showed lower efficacy of second-line T-DM1 in trastuzumab/pertuzumab pretreated, as compared with pertuzumab-naïve patients. Our findings may help delineate a more appropriate therapeutic strategy in HER2-positive metastatic BC. Prospective randomized trials addressing this topic are awaited.

BACKGROUND:In Western countries, ovarian cancer (OC) still represents the leading cause of gynecological cancer-related deaths, despite the remarkable gains in therapeutical options. Novel biomarkers of early diagnosis, prognosis definition and prediction of treatment outcomes are of pivotal importance. Prior studies have shown the potentials of micro-ribonucleic acids (miRNAs) as biomarkers for OC and other cancers.METHODS:We focused on the prognostic and/or predictive potential of miRNAs in OC by conducting a comprehensive array profiling of miRNA expression levels in ovarian tissue samples from 17 non-neoplastic controls, and 60 tumor samples from OC patients treated at the Regina Elena National Cancer Institute (IRE). A set of 54 miRNAs with differential expression in tumor versus normal samples (T/N-deregulated) was identified in the IRE cohort and validated against data from the Cancer Genoma Atlas (TCGA) related to 563 OC patients and 8 non-neoplastic controls. The prognostic/predictive role of the selected 54 biomarkers was tested in reference to survival endpoints and platinum resistance (P-res).RESULTS:In the IRE cohort, downregulation of the 2 miRNA-signature including miR-99a-5p and miR-320a held a negative prognostic relevance, while upregulation of miR-224-5p was predictive of less favorable event free survival (EFS) and P-res. Data from the TCGA showed that downregulation of 5 miRNAs, i.e., miR-150, miR-30d, miR-342, miR-424, and miR-502, was associated with more favorable EFS and overall survival outcomes, while miR-200a upregulation was predictive of P-res. The 9 miRNAs globally identified were all included into a single biologic signature, which was tested in enrichment analysis using predicted/validated miRNA target genes, followed by network representation of the miRNA-mRNA interactions.CONCLUSIONS:Specific dysregulated microRNA sets in tumor tissue showed predictive/prognostic value in OC, and resulted in a promising biological signature for this disease.