Updated overall survival from the MONALEESA-3 trial in postmenopausal women with HR+/HER2- advanced breast cancer receiving first-line ribociclib plus fulvestrant.

BACKGROUND: The phase III MONALEESA-3 trial included first- (1L) and second-line (2L) patients and demonstrated a significant overall survival (OS) benefit for ribociclib + fulvestrant in patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative (HR+/HER2-) advanced breast cancer (ABC) in the final protocol-specified and exploratory (longer follow-up) OS analyses. At the time of these analyses, the full OS benefit of 1L ribociclib was not completely characterized because the median OS (mOS) was not reached. As CDK4/6 inhibitor (CDK4/6i) + endocrine therapy (ET) is now a preferred option for 1L HR+/HER2- ABC, we report an exploratory analysis (median follow-up, 70.8 months; 14.5 months longer than the prior analysis) to fully elucidate the OS benefit in the MONALEESA-3 1L population. METHODS: Postmenopausal patients with HR+/HER2- ABC were randomized 2:1 to 1L/2L fulvestrant + ribociclib or placebo. OS in 1L patients (de novo disease or relapse > 12 months from completion of [neo]adjuvant ET) was assessed by Cox proportional hazards model and Kaplan-Meier methods. Progression-free survival 2 (PFS2) and chemotherapy-free survival (CFS) were analyzed. MONALEESA-3 is registered with ClinicalTrials.gov (NCT02422615). RESULTS: At data cutoff (January 12, 2022; median follow-up time, 70.8 months), mOS was 67.6 versus 51.8 months with 1L ribociclib versus placebo (hazard ratio (HR) 0.67; 95% CI 0.50-0.90); 16.5% and 8.6% of ribociclib and placebo patients, respectively, were still receiving treatment. PFS2 (HR 0.64) and CFS (HR 0.62) favored ribociclib versus placebo. Among those who discontinued treatment, 16.7% and 35.0% on ribociclib or placebo, respectively, received a subsequent CDK4/6i. No new safety signals were observed. CONCLUSIONS: This analysis of MONALEESA-3 reports the longest mOS thus far (67.6 months) for 1L patients in a phase III ABC trial. These results in a 1L population show that the OS benefit of ribociclib was maintained through extended follow-up, further supporting its use in HR+/HER2- ABC.

Cardiac safety of dual anti-HER2 blockade with pertuzumab plus trastuzumab in early HER2-positive breast cancer in the APHINITY trial.

BACKGROUND: Trastuzumab increases the incidence of cardiac events (CEs) in patients with breast cancer (BC). Dual blockade with pertuzumab (P) and trastuzumab (T) improves BC outcomes and is the standard of care for high-risk human epidermal growth factor receptor 2 (HER2)-positive early BC patients. We analyzed the cardiac safety of P and T in the phase III APHINITY trial. PATIENTS AND METHODS: Left ventricular ejection fraction (LVEF) ≥ 55% was required at study entry. LVEF assessment was carried out every 3 months during treatment, every 6 months up to month 36, and yearly up to 10 years. Primary CE was defined as heart failure class III/IV and a significant decrease in LVEF (defined as ≥10% from baseline and to <50%), or cardiac death. Secondary CE was defined as a confirmed significant decrease in LVEF, or CEs confirmed by the cardiac advisory board. RESULTS: The safety analysis population consisted of 4769 patients. With 74 months of median follow-up, CEs were observed in 159 patients (3.3%): 83 (3.5%) in P + T and 76 (3.2%) in T arms, respectively. Most CEs occurred during anti-HER2 therapy (123; 77.4%) and were asymptomatic or mildly symptomatic decreases in LVEF (133; 83.6%). There were two cardiac deaths in each arm (0.1%). Cardiac risk factors indicated were age > 65 years, body mass index ≥ 25 kg/m2, baseline LVEF between 55% and <60%, and use of an anthracycline-containing chemotherapy regimen. Acute recovery from a CE based on subsequent LVEF values was observed in 127/155 patients (81.9%). CONCLUSIONS: Dual blockade with P + T does not increase the risk of CEs compared with T alone. The use of anthracycline-based chemotherapy increases the risk of a CE; hence, non-anthracycline chemotherapy may be considered, particularly in patients with cardiovascular risk factors.

[CAR-T cells therapy in solid tumors : where are we now ?] / Les CAR-T cells dans le traitement des tumeurs solides : où en sommes-nous ?

Chimeric antigen receptor T cells (also known as CAR-T cells) have already made their way into the therapeutic arsenal of specific hematological cancers, significantly improving the prognosis of patients. The prospect of such an innovative and effective treatment in solid tumors is very attractive. For this reason, several clinical studies have been initiated. Unfortunately, the antigenic heterogeneity and microenvironmental hostility of these solid tumors currently limit the effectiveness of CAR-T cells. New strategies are being sought to counteract these therapeutic obstacles.

Les lymphocytes T porteurs d'un récepteur antigénique chimérique, appelés CAR-T cells, ont déjà fait leur chemin dans l'arsenal thérapeutique de certains cancers hématologiques, améliorant significativement le pronostic des patients. La perspective d'un tel traitement, aussi innovant qu'efficace, dans les tumeurs solides est très attrayante. C'est la raison pour laquelle plusieurs études cliniques ont vu le jour. Malheureusement, l'hétérogénéité antigénique et l'hostilité micro-environnementale de ces tumeurs solides limitent actuellement l'efficacité des CAR-T cells. De nouvelles stratégies sont recherchées pour contrer ces obstacles thérapeutiques.

Recurrent or primary metastatic cervical cancer: current and future treatments.

Despite screening programs for early detection and the approval of human papillomavirus vaccines, around 6% of women with cervical cancer (CC) are discovered with primary metastatic disease. Moreover, one-third of the patients receiving chemoradiation followed by brachytherapy for locally advanced disease will have a recurrence. At the end, the vast majority of recurrent or metastatic CC not amenable to locoregional treatments are considered incurable disease with very poor prognosis. Historically, cisplatin monotherapy, then a combination of cisplatin and paclitaxel were considered the standard of care. Ten years ago, the addition of bevacizumab to chemotherapy demonstrated favorable data in terms of response rate and overall survival. Even with this improvement, novel therapies are needed for the treatment of recurrent CC in first as well as later lines. In the last decades, a better understanding of the interactions between human papillomavirus infection and the host immune system response has focused interest on the use of immunotherapeutic drugs in CC patients. Indeed, immune checkpoint inhibitors (pembrolizumab, cemiplimab, and others) have recently emerged as novel therapeutic pillars that could provide durable responses with impact on overall survival in patients in the primary (in addition to chemotherapy) or recurrent (monotherapy) settings. Tisotumab vedotin, an antibody-drug conjugate targeting the tissue factor, is another emerging drug. Several trials in monotherapy or in combination with immunotherapy, chemotherapy, or bevacizumab showed very promising results. There is a high need for more potent biomarkers to better accurately determine which patients would receive the greatest benefit from all these aforementioned drugs, but also to identify patients with specific molecular characteristics that could benefit from other targeted therapies. The Cancer Genome Atlas Research Network identified several genes significantly mutated, potentially targetable. These molecular data have highlighted the molecular heterogeneity of CC.

[Inflammation and cancer : a complex two-way relationship]. / Inflammation et cancer : une relation complexe à double sens.

The relationships between inflammation and cancer are known since the original work by Virchow in the 19th century and have been largely confirmed after-wards. An interesting question is what might be the primum movens. Numerous clinical observations have shown that a chronic inflammatory state, as that observed with some infections, toxic agents or dysimmune diseases, may be associated with the development of cancer later on. Besides, cancer is generally accompanied by an inflammatory microenvironment, with numerous cellular and humoral components, which promotes both tumorigenesis and the invasivity of the tumour. This article aims at defining the pathophysiology of this association, with a description of underlying mechanisms and mediators, and at determining possible therapeutic implications.

: Les relations entre inflammation et cancer sont connues depuis les travaux pionniers de Virchow au 19ème siècle et ont été largement confirmées depuis lors. En fait, il s'agit d'une relation à double sens et la question est de savoir quel est le primum movens. De nombreuses observations cliniques ont montré qu'un état inflammatoire chronique, tel qu'on peut l'observer avec certaines infections, certains toxiques ou encore des maladies dysimmunitaires, peut être associé, à terme, au développement d'un cancer. Par ailleurs, le cancer s'accompagne généralement d'un microenvironnement inflammatoire, avec de nombreuses composantes cellulaires et humorales, qui favorise la tumorigenèse et l'invasivité de la tumeur. Cet article a pour objectif de définir la physiopathologie de cette association, en décrivant les mécanismes et médiateurs sous-jacents, et d'en déterminer les éventuelles implications thérapeutiques.

Continuous versus intermittent extended adjuvant letrozole for breast cancer: final results of randomized phase III SOLE (Study of Letrozole Extension) and SOLE Estrogen Substudy.

BACKGROUND: Late recurrences in postmenopausal women with hormone receptor-positive breast cancers remain an important challenge. Avoidance or delayed development of resistance represents the main objective in extended endocrine therapy (ET). In animal models, resistance was reversed with restoration of circulating estrogen levels during interruption of letrozole treatment. This phase III, randomized, open-label Study of Letrozole Extension (SOLE) studied the effect of extended intermittent letrozole treatment in comparison with continuous letrozole. In parallel, the SOLE estrogen substudy (SOLE-EST) analyzed the levels of estrogen during the interruption of treatment. PATIENTS AND METHODS: SOLE enrolled 4884 postmenopausal women with hormone receptor-positive, lymph node-positive, operable breast cancer between December 2007 and October 2012 and among them, 104 patients were enrolled in SOLE-EST. They must have undergone local treatment and have completed 4-6 years of adjuvant ET. Patients were randomized between continuous letrozole (2.5 mg/day orally for 5 years) and intermittent letrozole treatment (2.5 mg/day for 9 months followed by a 3-month interruption in years 1-4 and then 2.5 mg/day during all of year 5). RESULTS: Intention-to-treat population included 4851 women in SOLE (n = 2425 in the intermittent and n = 2426 in the continuous letrozole groups) and 103 women in SOLE-EST (n = 78 in the intermittent and n = 25 in the continuous letrozole groups). After a median follow-up of 84 months, 7-year disease-free survival (DFS) was 81.4% in the intermittent group and 81.5% in the continuous group (hazard ratio: 1.03, 95% confidence interval: 0.91-1.17). Reported adverse events were similar in both groups. Circulating estrogen recovery was demonstrated within 6 weeks after the stop of letrozole treatment. CONCLUSIONS: Extended adjuvant ET by intermittent administration of letrozole did not improve DFS compared with continuous use, despite the recovery of circulating estrogen levels. The similar DFS coupled with previously reported quality-of-life advantages suggest intermittent extended treatment is a valid option for patients who require or prefer a treatment interruption.

Ribociclib plus fulvestrant for postmenopausal women with hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer in the phase III randomized MONALEESA-3 trial: updated overall survival.

BACKGROUND: Ribociclib plus fulvestrant demonstrated significant progression-free survival (PFS) and overall survival (OS) benefits in patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative (HR+/HER2-) advanced breast cancer (ABC). Here we present a new landmark in survival follow-up for a phase III cyclin-dependent kinases 4 and 6 inhibitor clinical trial in patients with ABC (median, 56.3 months). PATIENTS AND METHODS: This phase III, randomized, double-blind, placebo-controlled trial was conducted at 174 sites (30 countries). Patients were men and postmenopausal women (age ≥18 years) with histologically/cytologically confirmed HR+/HER2- ABC. Patients could have received ≤1 line of endocrine therapy (ET) but no chemotherapy for ABC. Patients, assigned 2:1, were stratified by the presence/absence of liver/lung metastases and previous ET. Patients received intramuscular fulvestrant (500 mg, day 1 of each 28-day cycle plus day 15 of cycle 1) with oral ribociclib (600 mg/day, 3 weeks on, 1 week off) or placebo. Efficacy analyses were by intention to treat. Safety was assessed in patients receiving ≥1 dose study treatment. OS was a secondary endpoint. MONALEESA-3 is registered with ClinicalTrials.gov (NCT02422615; no longer enrolling). RESULTS: Between 18 June 2015 and 10 June 2016, 726 patients were randomly assigned (484, ribociclib; 242, placebo). At data cut-off (30 October 2020), median OS (mOS) was 53.7 months (ribociclib) versus 41.5 months (placebo) [hazard ratio (HR), 0.73; 95% confidence interval (CI) 0.59-0.90]. Subgroup analyses were consistent with overall population. In the first-line setting, most patients in the ribociclib arm (∼60%) lived longer than median follow-up; mOS was 51.8 months in the placebo arm (HR, 0.64; 95% CI 0.46-0.88). In the second-line setting, mOS was 39.7 months (ribociclib) versus 33.7 months (placebo) (HR, 0.78; 95% CI 0.59-1.04). No apparent drug-drug interaction between ribociclib and fulvestrant or new safety signals were observed. CONCLUSIONS: This analysis reported extended OS follow-up in MONALEESA-3. mOS was ∼12 months longer in patients with HR+/HER2- ABC treated with ribociclib plus fulvestrant compared with fulvestrant monotherapy.

[Editorial. Oncology, at a turning point in its history]. / Éditorial. L'oncologie, à un tournant de son histoire.

No abstract available.

Randomized controlled trial of a group intervention combining self-hypnosis and self-care: secondary results on self-esteem, emotional distress and regulation, and mindfulness in post-treatment cancer patients.

PURPOSE: Cancer patients often report low self-esteem and high emotional distress. Two factors seem particularly linked to these symptoms: emotion regulation strategies and mindfulness. The interest of hypnosis and self-care to relieve these symptoms is not well documented. Our randomized controlled trial aimed at assessing the effect of a group intervention combining self-hypnosis and self-care on self-esteem, emotional distress, emotion regulation, and mindfulness abilities of post-treatment cancer patients, as well as investigating the links between these variables. METHODS: One hundred and four patients who had suffered from cancer were randomized into the intervention group (N = 52) and the wait-list control group (N = 52). They had to answer questionnaires before (T1) and after the intervention (T2). Nine men were excluded from the analyses, leading to a final sample of 95 women with cancer. Group-by-time changes were assessed with MANOVA, and associations with self-esteem and emotional distress were investigated with hierarchical linear regression models. RESULTS: Participants in the intervention group (mean age = 51.65; SD = 12.54) reported better self-esteem, lower emotional distress, a decreased use of maladaptive emotion regulation strategies, and more mindfulness abilities after the intervention, compared to the WLCG. This increase in mindfulness explained 33% of the improvement of self-esteem and 41.6% of the decrease of emotional distress in the intervention group. Self-esteem and emotional distress also predicted each other. CONCLUSION: Our study showed the efficacy of our hypnosis-based intervention to improve all the investigated variables. Mindfulness predicted the improvement of self-esteem and emotional distress. The primary impact of our intervention on mindfulness abilities seems to explain, at least in part, its efficacy. Registration: ClinicalTrials.gov (NCT03144154). Retrospectively registered on the 1st of May, 2017.

[Organisation of cancer care during the COVID-19 pandemic : experience from CHU Liège]. / Organisation des soins en cancérologie dans le contexte de la COVID-19 : expérience au CHU de Liège.

The COVID-19 pandemic has had a major impact in the world of Oncology. Surprised by the rapidity of the extension of the pandemic, the oncological department had to be reorganised in a very short time period in a hospital which had the primary objective to treat infected patients. The author describes how with the help of an international network and local research projects all efforts have been done to offer the best patient's care in a secure environment.

La pandémie de la COVID-19 a eu un impact majeur sur l'organisation des soins en Oncologie. Surpris par la rapidité des événements, il fallait redéfinir en urgence le fonctionnement d'un service d'Oncologie médicale dans un hôpital qui devait, en priorité, s'occuper de la prise en charge des patients infectés par le SARS-CoV-2. L'auteur décrit comment, avec l'aide d'un réseau international et de projets scientifiques locaux, tous les efforts ont été réalisés pour assurer la continuité des soins dans les meilleures conditions de sécurité du patient.

[Evolution of systemic anti-cancer therapies]. / Evolution des thérapies anti-cancéreuses systémiques.

Before the advent of chemotherapy in the 1940s, cancer treatment was dominated by surgery and radiation therapy. The developments of targeted anti-cancer therapies in the 2000s followed by immunotherapy have largely changed the treatment landscape in particular in the metastatic setting. Here we provide a history of these advances.

Avant l'avènement de la chimiothérapie dans les années 1940, le traitement du cancer était dominé par la chirurgie et la radiothérapie. Il a fallu attendre les années 2000 pour voir apparaître le développement des thérapies anti-cancéreuses ciblées, puis de l'immunothérapie. Ces traitements systémiques ont fortement modifié la prise en charge des patients en oncologie et, en particulier, au stade métastatique. Nous dressons ici un historique de ces avancées.

Everolimus plus exemestane in hormone-receptor-positive, HER2-negative locally advanced or metastatic breast cancer: incidence and time course of adverse events in the phase IIIb BALLET population.

BACKGROUND: The addition of everolimus to exemestane therapy significantly improves progression-free survival in postmenopausal patients with hormone-receptor (HR)-positive HER2-negative endocrine-resistant breast cancer. However, the safety profile of this schedule still might be optimized. METHODS: Patients included in the BALLET trial were assessed. The objectives of this analysis were to provide additional information on the safety profile of this schedule depending on prior anticancer therapies and to characterize the time course of adverse events (AEs) and serious AEs (SAEs) of clinical interest throughout the study period. Non-infectious pneumonitis (NIP), stomatitis, asthenia and weight loss were selected as AEs of clinical interest. RESULTS: The safety population of this analysis comprised 2131 patients. There were similar incidences of AEs and SAEs of clinical interest regardless of previous anticancer therapies. Most stomatitis and asthenia events occurred within the first three months. Incidence of weight loss appeared to plateau except in the case of grade 3-4 events, which occurred rarely. The incidence of any grade NIP (between 2 to 6%) and grade 3-4 NIP (between 0 to 1%) was low across the study, but steady. CONCLUSIONS: Everolimus plus exemestane is a well-known therapeutic option for aromatase inhibitor pretreated advanced breast cancer patients, and its toxicity profile is similar to that described in previous studies. Close monitoring, especially within the first three months, early intervention with preventive measures and patient education to help recognize the first signs and symptoms of AEs, will help to reduce their incidence and severity.

Determining clinically important differences in health-related quality of life in older patients with cancer undergoing chemotherapy or surgery.

PURPOSE: Using the EORTC Global Health Status (GHS) scale, we aimed to determine minimal clinically important differences (MCID) in health-related quality of life (HRQOL) changes for older cancer patients with a geriatric risk profile, as defined by the geriatric 8 (G8) health screening tool, undergoing treatment. Simultaneously, we assessed baseline patient characteristics prognostic for HRQOL changes. METHODS: Our analysis included 1424 (G8 ≤ 14) older patients with cancer scheduled to receive chemotherapy (n = 683) or surgery (n = 741). Anchor-based methods, linking the GHS score to clinical indicators, were used to determine MCID between baseline and follow-up at 3 months. A threshold of 0.2 standard deviation (SD) was used to exclude MCID estimates too small for interpretation. Logistic regressions analysed baseline patient characteristics prognostic for HRQOL changes. RESULTS: The 15-item Geriatric Depression Scale (GDS15), Visual Analogue Scale (VAS) for Fatigue and ECOG Performance Status (PS) were selected as clinical anchors. In the surgery group, MCID estimates for improvement and deterioration were ECOG PS (5*, 11*), GDS15 (5*, 2) and VAS Fatigue (3, 9*). In the chemotherapy group, MCID estimates for improvement and deterioration were ECOG PS (8*, 7*), GDS15 (5, 4) and VAS Fatigue (5, 5*). Estimates with * were > 0.2 SD threshold. Patients experiencing pain or malnutrition (surgery group) or fatigue (chemotherapy group) at baseline showed a significantly stable or improved HRQOL (p < 0.05) after their treatment. CONCLUSION: The reported MCID for improvement and deterioration depended on the anchor used and treatment received. The estimates can be used to evaluate significant changes in HRQOL and to determine sample sizes in clinical trials.

Adherence to geriatric assessment-based recommendations in older patients with cancer: a multicenter prospective cohort study in Belgium.

Background: In the general older population, geriatric assessment (GA)-guided treatment plans can improve overall survival, quality of life and functional status (FS). In GA-related research in geriatric oncology, studies mainly focused on geriatric screening and GA but not on geriatric recommendations, interventions and follow-up. The aim of this study was to investigate the adherence to geriatric recommendations and subsequent actions undertaken in older patients with cancer. Patient and methods: A prospective Belgian multicenter (N = 22) cohort study included patients ≥70 years with a malignant tumor upon oncologic treatment decision. Patients with an abnormal result on the geriatric screening (G8 ≤14/17) underwent GA. Geriatric recommendations were formulated based on GA results. At follow-up the adherence to geriatric recommendations was documented including a description of actions undertaken. Results: From November 2012 till February 2015, G8 screening was carried out in 8451 patients, of which 5838 patients had an abnormal result. Geriatric recommendations data were available for 5631 patients. Geriatric recommendations were made for 4459 patients. Geriatric interventions data were available for 4167 patients. A total of 12 384 geriatric recommendations were made. At least one different geriatric recommendation was implemented in 2874 patients. A dietician, social worker and geriatrician intervened most frequently for problems detected on the nutritional, social and functional domain. A total of 7569 actions were undertaken for a total of 5725 geriatric interventions, most frequently nutritional support and supplements, extended home care and psychological support. Conclusions: This large-scale Belgian study focuses on the adherence to geriatric recommendations and subsequent actions undertaken and contributes to the optimal management of older patients with cancer. We identified the domains for which geriatric recommendations are most frequently made and adhered to, and which referrals to other health care workers and facilities are frequently applied in the multidisciplinary approach of older patients with cancer.

Communication of healthcare professionals: Is there ageism?

Elderspeak is often used when talking to older individuals and is characterised by a slower and/or louder speech, a patronising tone, etc. A part of the reason of such communication can be found in the actual context of negative view of ageing. However, the link between view of ageing and elderspeak has never been objectively studied in oncology. Therefore, 40 healthcare professionals (physicians and medical students) record a podcast where they have to explain an endocrine therapy to two fictional patients (40- vs. 70-year old). Results show that when participants explained the treatment to the older patient, they used shorter utterances and made more repetitions. They also evoked fewer side effects such as sexual issues. Moreover, reduction in length of utterances and of word-per-minute rate was observed for older patient when participants have a positive view of ageing but for both patients when they have a negative view of ageing. In conclusion, physicians and medical students used elderspeak when they explained a treatment to older patients. Participants with a more negative view of ageing also unconsciously talked slower and made shorter utterances to a 40 -year-old patient.

A randomized phase II study evaluating different maintenance schedules of nab-paclitaxel in the first-line treatment of metastatic breast cancer: final results of the IBCSG 42-12/BIG 2-12 SNAP trial.

Background: The phase II SNAP trial was designed to evaluate the efficacy of alternative chemotherapy schedules for prolonged administration in HER2-negative metastatic breast cancer (MBC), after a short induction at conventional doses. Patients and methods: Between April 2013 and August 2015, 258 women untreated with chemotherapy for MBC were randomly assigned to receive three different maintenance chemotherapy schedules after three cycles of identical induction chemotherapy: arm A, nab-paclitaxel 150 mg/m2 days 1 and 15 Q28; arm B, nab-paclitaxel 100 mg/m2 days 1, 8 and 15 Q28; arm C, nab-paclitaxel 75 mg/m2 days 1, 8, 15 and 22 Q28. Induction was three cycles nab-paclitaxel 150/125 mg/m2, days 1, 8 and 15 Q28. The primary objective was to evaluate the efficacy of each maintenance schedule, in terms of progression-free survival (PFS), as compared with the historical reference of 7-month median PFS reported by previous studies with first-line docetaxel. One-sample, one-sided log-rank tests were utilized. Quality-of-life (QoL) evaluation was carried out, and the global indicator for physical well-being was defined as the primary QoL end point; completion rates of QoL forms were >90%. Results: In total, 255 patients were assessable for the primary end point. After 18.2-month median follow-up, 182 PFS events were observed. Median PFS was 7.9 months [90% confidence interval CI 6.8-8.4] in arm A, 9.0 months (90% CI 8.1-10.9) in arm B and 8.5 months (90% CI 6.7-9.5) in arm C. PFS in arm B was significantly longer than the historical reference of first-line docetaxel (P = 0.03). Grade ≥2 sensory neuropathy was reported in 37.9%, 36.1% and 31.2% of the patients in arm A, B and C, respectively (Grade ≥3 in 9.1%, 5.6% and 6.6% of the patients, respectively). Noteworthy, the QoL scores for sensory neuropathy did not worsen with prolonged nab-paclitaxel administration in any of the maintenance arms. Conclusion: The SNAP trial demonstrated that alternative nab-paclitaxel maintenance schedules with reduced dosages after a short induction at conventional doses are feasible and active in the first-line treatment of MBC. Registration: ClinicalTrials.gov NCT01746225.

Phase II study of buparlisib (BKM120) and trastuzumab in patients with HER2+ locally advanced or metastatic breast cancer resistant to trastuzumab-based therapy.

PURPOSE: A Phase Ib study in patients with trastuzumab-resistant, human epidermal growth factor receptor-2- (HER2)-positive advanced breast cancer defined the recommended Phase II dose of buparlisib as 100 mg/day in combination with 2 mg/kg weekly trastuzumab, and reported preliminary signs of clinical activity. Here we present results from the Phase II portion. METHODS: Patients with trastuzumab-resistant, HER2-positive advanced breast cancer received buparlisib plus trastuzumab. Study endpoints included safety/tolerability and antitumour activity. The study was extended to include a Phase Ib dose-escalation phase, in which patients with progressive brain metastases also received capecitabine. RESULTS: In the Phase II portion, of 50 patients treated with buparlisib and trastuzumab, the most common (≥ 30%) all-grade adverse events (AEs) were diarrhoea (54%), nausea (48%), decreased appetite, increased alanine aminotransferase (36% each), increased aspartate aminotransferase (34%), fatigue, rash (32% each), cough and hyperglycemia (30% each). One (2%) patient achieved complete response and four (8%) patients had confirmed partial responses [PR; including two patients with phosphatidylinositol 3-kinase (PI3 K) pathway-activated tumours]. Overall response rate (ORR) was 10%: the primary endpoint (ORR ≥ 25%) was therefore not met. In the Phase Ib portion, all patients with measurable brain lesions at baseline showed tumour shrinkage to some degree; due to low enrollment, maximum tolerated dose of buparlisib in combination with trastuzumab and capecitabine was not determined. CONCLUSION: Buparlisib plus trastuzumab, as a chemotherapy-free regimen, demonstrated an acceptable safety profile but limited efficacy in patients with heavily pretreated, trastuzumab-resistant HER2-positive breast cancer, and in patients with progressive brain metastases also receiving capecitabine.

Safety of everolimus plus exemestane in patients with hormone-receptor-positive, HER2-negative locally advanced or metastatic breast cancer progressing on prior non-steroidal aromatase inhibitors: primary results of a phase IIIb, open-label, single-arm, expanded-access multicenter trial (BALLET).

BACKGROUND: This European phase IIIb, expanded-access multicenter trial evaluated the safety of EVE plus EXE in a patient population similar to BOLERO-2. PATIENTS AND METHODS: Post-menopausal women aged ≥18 years with hormone receptor-positive, human epidermal growth factor-receptor-2-negative advanced breast cancer (ABC) recurring/progressing during/after prior non-steroidal aromatase inhibitors were enrolled. The primary objective was safety of EVE plus EXE based on frequency of adverse events (AEs), and serious AEs (SAEs). The secondary objective was to evaluate AEs of grade 3/4 severity. RESULTS: The median treatment duration was 5.1 months [95% confidence interval (CI) 4.8-5.6] for EVE and 5.3 months (95% CI 4.8-5.6) for EXE. Overall, 2131 patients were included in the analysis; 81.8% of patients experienced EVE- or EXE-related or EVE/EXE-related AEs (investigator assessed); 27.2% were of grade 3/4 severity. The most frequently reported non-hematologic AEs were (overall %, % EVE-related) stomatitis (52.8%; 50.8%) and asthenia (22.8%; 14.6%). The most frequently reported hematologic AEs were (overall %, % EVE-related) anemia (14.4%; 8.1%) and thrombocytopenia (5.9%; 4.6%). AE-related treatment discontinuations were higher in elderly (≥70 years) versus non-elderly patients (23.8% versus 13.0%). The incidence of EVE-related AEs in both elderly and non-elderly patients appeared to be lower in first-line ABC versus later lines. The incidence of AEs (including stomatitis/pneumonitis) was independent of BMI status (post hoc analysis). Overall, 8.5% of patients experienced at least one EVE-related SAE. Of the 121 on-treatment deaths (5.7%), 66 (3.1%) deaths were due to disease progression and 46 (2.2%) due to AEs; 4 deaths were suspected to be EVE-related. CONCLUSIONS: This is the largest ever reported safety dataset on a general patient population presenting ABC treated with EVE plus EXE and included a sizeable elderly subset. Although the patients were more heavily pretreated, the safety profile of EVE plus EXE in BALLET was consistent with BOLERO-2. CLINICAL TRIAL REGISTRATION: EudraCT Number: 2012-000073-23.

A Belgian Survey on Geriatric Assessment in Oncology Focusing on Large-Scale Implementation and Related Barriers and Facilitators.

OBJECTIVES: The aim of this study is to describe a large-scale, Belgian implementation project about geriatric assessment (=GA) in daily oncology practice and to identify barriers and facilitators for implementing GA in this setting. Design / setting / participants: The principal investigator of every participating hospital (n=22) was invited to complete a newly developed questionnaire with closed- and open-ended questions. The closed-ended questions surveyed how GA was implemented. The open-ended questions identified barriers and facilitators for the implementation of GA in daily oncology practice. Descriptive statistics and conventional content analysis were performed as appropriate. RESULTS: Qualifying criteria (e.g. disease status and cancer type) for GA varied substantially between hospitals. Thirteen hospitals (59.1%) succeeded to screen more than half of eligible patients. Most hospitals reported that GA data and follow-up data had been collected in almost all screened patients. Implementing geriatric recommendations and formulating new geriatric recommendations at the time of follow-up are important opportunities for improvement. The majority of identified barriers were organizational, with high workload, lack of time or financial/staffing problems as most cited. The most cited facilitators were all related to collaboration. CONCLUSION: Interventions to improve the implementation of GA in older patients with cancer need to address a wide range of factors, with organization and collaboration as key elements. All stakeholders, seeking to improve the implementation of GA in older patients with cancer, should consider and address the identified barriers and facilitators.