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Patients presenting with hormone receptor‐positive (HR+), human epidermal growth factor receptor 2‐negative (HER2–) metastatic breast cancer (MBC) are usually treated with endocrine therapy (ET), except if there is a concern about endocrine resistance or a need to achieve rapid disease control due to visceral crisis. The combination of CDK4/6 inhibitor + ET has now replaced single‐agent ET as the standard first‐line treatment; and it can also be considered a standard option in the second‐line setting. This review briefly summarizes recently reported efficacy findings from the key phase III clinical trials of CDK4/6 inhibitor + ET in patients with HR+/HER2– MBC, including evidence that adding a CDK4/6 inhibitor to ET improves overall survival and does so without reducing patients' quality of life. There is still much to learn regarding the use of CDK4/6 inhibitors and how they may be optimally integrated into clinical practice. In particular, there is a need for specific biomarkers that help predict the likelihood of response or resistance to CDK4/6 inhibitor therapy; and for data to guide treatment decisions when a patient's disease progresses on a CDK4/6 inhibitor. [ABSTRACT FROM AUTHOR]

Treatment strategies for hormone receptor‐positive (HR+), human epidermal growth factor receptor 2‐negative (HER2–) metastatic breast cancer in young women (<40 years at diagnosis) have traditionally been extrapolated from data obtained from trials conducted either exclusively or predominantly in the postmenopausal setting. These young patients are usually treated with ovarian function suppression (OFS) + endocrine therapy (ET) ± targeted therapy, except if there is a concern about endocrine resistance or a need to gain rapid disease control due to the onset of visceral crisis. This review examines evidence that supports the use of a cyclin‐dependent kinase 4/6 inhibitor, in combination with OFS and ET, when treating premenopausal or perimenopausal women with HR+/HER2– metastatic breast cancer. This includes data from the MONALEESA‐7 study (treating only premenopausal/perimenopausal women in the first‐line setting), and the results of subgroup analyses from the PALOMA‐3 and MONARCH‐2 trials. We also consider a number of age‐specific challenges that younger breast cancer patients can face, highlighting the importance of a multidisciplinary approach to ongoing care. [ABSTRACT FROM AUTHOR]

Background: In the ongoing, phase 3 PACIFIC trial, durvalumab improved the primary endpoints of progression-free survival and overall survival compared with that for placebo, with similar safety, in patients with unresectable, stage III non-small-cell lung cancer. In this analysis, we aimed to evaluate one of the secondary endpoints, patient-reported outcomes (PROs).Methods: PACIFIC is an ongoing, international, multicentre, double-blind, randomised, controlled, phase 3 trial. Eligible patients were aged at least 18 years, had a WHO performance status of 0 or 1, with histologically or cytologically documented stage III, unresectable non-small-cell lung cancer, for which they had received at least two cycles of platinum-based chemoradiotherapy, with no disease progression after this treatment. We randomly assigned patients (2:1) using an interactive voice response system and a blocked design (block size=3) stratified by age, sex, and smoking history to receive 10 mg/kg intravenous durvalumab or matching placebo 1-42 days after concurrent chemoradiotherapy, then every 2 weeks up to 12 months. The primary endpoints of progression-free survival and overall survival have been reported previously. PROs were a prespecified secondary outcome. We assessed PRO symptoms, functioning, and global health status or quality of life in the intention-to-treat population with the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) version 3 and its lung cancer module, the Quality of Life Questionnaire-Lung Cancer 13 (QLQ-LC13) at the time of random allocation to groups, at weeks 4 and 8, every 8 weeks until week 48, and then every 12 weeks until progression. Changes from baseline to 12 month in key symptoms were analysed with mixed model for repeated measures (MMRM) and time-to-event analyses. A 10-point or greater change from baseline (deterioration or improvement) was deemed clinically relevant. This study is registered with ClinicalTrials.gov, NCT02125461, and EudraCT, 2014-000336-42.Findings: Between May 9, 2014, and April 22, 2016, 476 patients were assigned to receive durvalumab, and 237 patients were assigned to receive placebo. As of March 22, 2018, the median follow-up was 25·2 months (IQR 14·1-29·5). More than 79% of patients given durvalumab and more than 82% of patients given placebo completed questionnaires up to week 48. Between baseline and 12 months, the prespecified longitudinal PROs of interest, cough (MMRM-adjusted mean change 1·8 [95% CI 0·06 to 3·54] in the durvalumab group vs 0·7 [-1·91 to 3·30] in the placebo group), dyspnoea (3·1 [1·75 to 4·36] vs 1·4 [-0·51 to 3·34]), chest pain (-3·1 [-4·57 to -1·60] vs -3·5 [-5·68 to -1·29]), fatigue (-3·0 [-4·53 to -1·50] vs -5·2 [-7·45 to -2·98]), appetite loss (-5·8 [-7·28 to -4·36] vs -7·0 [-9·17 to -4·87]), physical functioning (0·1 [-1·10 to 1·28] vs 2·0 [0·22 to 3·73]), and global health status or quality of life (2·6 [1·21 to 3·94] vs 1·8 [-0·25 to 3·81]) remained stable with both treatments, with no clinically relevant changes from baseline. The between-group differences in changes from baseline to 12 months in cough (difference in adjusted mean changes 1·1, 95% CI -1·89 to 4·11), dyspnoea (1·6, -0·58 to 3·87), chest pain (0·4, -2·13 to 2·93), fatigue (2·2, -0·38 to 4·78), appetite loss (1·2, -1·27 to 3·67), physical functioning (-1·9, -3·91 to 0·15), or global health status or quality of life (0·8, -1·55 to 3·14) were not clinically relevant. Generally, there were no clinically important between-group differences in time to deterioration of prespecified key PRO endpoints.Interpretation: Our findings suggest that a clinical benefit with durvalumab can be attained without compromising PROs. This result is of note because the previous standard of care was observation alone, with no presumed detriment to PROs.Funding: AstraZeneca. [ABSTRACT FROM AUTHOR]

Background: Durvalumab following concurrent chemoradiotherapy is standard treatment for unresectable stage III non‐small‐cell lung cancer based on the results of the PACIFIC trial. Based on trial criteria, not all patients are eligible for durvalumab in routine clinical practice. Methods: We evaluated eligibility for durvalumab in a real‐world clinical setting and the impact of eligibility on outcomes. Consecutive patients treated with concurrent chemoradiotherapy at two tertiary centers between January 2015 and June 2022 were assessed. Clinical characteristics and outcomes were evaluated based on eligibility criteria for the PACIFIC trial. Results: A total of 126 patients were included. Seventy patients (56%) were eligible for durvalumab. Ineligibility was associated with shorter progression‐free survival of 9.7 months versus 18.4 months (hazard ratio [HR] 0.61, 95% confidence interval [CI] 0.39–0.95, p = 0.029) and overall survival of 26.4 months versus 58.7 months (HR 0.47, 95% CI 0.28–0.80, p = 0.005). Common reasons for ineligibility were history of previous malignancy (32%) and progressive disease or death during chemoradiotherapy (25%). Ineligible patients who received durvalumab had similar outcomes to eligible patients who received durvalumab. Conclusions: In a real‐world cohort, adjuvant durvalumab is safe and beneficial in a substantial proportion of patients who would not have been eligible for the PACIFIC trial. [ABSTRACT FROM AUTHOR]

With improved diagnosis and treatments, a greater percentage of breast cancer patients are achieving long-term survival. Consequently, long-term cardiotoxicity secondary to chemotherapy has become more prevalent, warranting improved cardiac surveillance. We evaluated changes in left atrial (LA) strain in breast cancer patients immediately post anthracycline (AC) therapy to assess its utility as a marker of diastolic dysfunction. This was a prospective cohort study of 128 consecutive human epidermal growth factor receptor 2 (HER2)-negative breast cancer patients who underwent transthoracic echocardiography prior to and immediately post AC treatment. Traditional left ventricular (LV) systolic and diastolic parameters and LA volumes were evaluated; additionally, LV global longitudinal strain (LV GLS) and LA phasic strain were measured. All patients had normal LV ejection fraction (>53%) post AC, though LV GLS was significantly reduced. Peak E and é velocities were reduced post AC, with no change in LA volumes. LA reservoir strain (LAS RES 34.8% vs 31.5%, p<0.001) and conduit strain (LAS CD 17.2% vs 14.4%, p<0.001) were significantly lower post AC and correlated modestly with LV diastolic parameters. Reduction in LA strain post AC was evident even in patients with preserved LV systolic and diastolic function. More patients demonstrated alteration in diastolic function (≥15% reduction in LAS RES from baseline) (32%) compared to alteration in systolic function (≥15% reduction in LV GLS) (23%). LA strain is a promising marker of early diastolic dysfunction. We demonstrate its potential utility in surveillance of breast cancer patients treated with AC. [Display omitted] [ABSTRACT FROM AUTHOR]

The EMS1 and CCND1 genes at chromosome 11q13 are amplified in about 15% of primary breast cancers but appear to confer different phenotypes in ER positive and ER negative tumours. Since there are no published data on EMS1 expression in large series of breast cancers we examined the relationship of EMS1 expression with EMS1 gene copy number and expression of mRNAs for cyclin D1 and ER. In a subset of 129 patients, where matched tumour RNA and DNA was available, EMS1 mRNA overexpression was associated predominantly with gene amplification (P=0.0061), whereas cyclin D1 mRNA overexpression was not (P=0.3142). In a more extensive series of 351 breast cancers, there was no correlation between cyclin D1 and EMS1 expression in the EMS1 and cyclin D1 overexpressors (P=0.3503). Although an association between EMS1 mRNA expression and ER positivity was evident (P=0.0232), when the samples were divided into quartiles of EMS1 or cyclin D1 mRNA expression, the increase in the proportion of ER positive tumours in the ascending EMS1 mRNA quartiles was not statistically significant (P=0.0951). In marked contrast there was a significant stepwise increase in ER positivity in ascending quartiles of cyclin D1 mRNA (P=0.030). A potential explanation for this difference was provided by the observation that in ER positive breast cancer cells oestradiol treatment resulted in increased cyclin D1 gene expression but was without effect on EMS1. The relationship between EMS1 expression and clinical outcome was examined in a subset of 234 patients with median follow-up of 74 months. High EMS1 expression was associated with age >50 years (P=0.0001), postmenopausal status (P=0.0008), lymph node negativity (P=0.019) and an apparent trend for worse prognosis in the ER negative subgroup. These data demonstrate that overexpression of EMS1 mRNA is largely due to EMS1 gene amplification, is independent of cyclin D1 and ER expression and, in contrast to cyclin D1, is not regulated by oestrogen. Independent overexpression of these genes may confer different phenotypes and disease outcomes in breast cancer as has been inferred from recent studies of EMS1 and CCND1 gene amplification. [ABSTRACT FROM AUTHOR]

Chromosome 11q13 is amplified in about 13% of primary breast cancers. CCND1, encoding the cell cycle regulatory gene cyclin D1, and EMS1, encoding a filamentous actin binding protein, are favoured candidate onocogenes, whereas INT-2 is an unexpressed gene at this locus. In this study we tested the possibility that different regions of this large amplicon could be independently amplified and subsequently defined the phenotype of EMS1 amplified tumours in a series of 961 primary breast carcinomas. Using DNA slot blots, EMS1 was amplified in 15.2% of samples: 5.4% were coamplified for CCND1; 7.9% coamplified for INT-2 and 6.7% showed EMS1 amplification alone. The degree of amplification of CCND1 and INT-2 was highly correlated (P=0.0001). In contrast, no such relationship existed between EMS1 and CCND1 or INT-2 amplification, demonstrating independent amplification of EMS1 in 44% of amplified tumours. EMS1 amplification (twofold increase in copy number) was positively correlated with patient age 50 years (P=0.025), ER positivity (P=0.022), PgR positivity (P=0.018), and was negatively correlated with HER-2/neu (c-erbB2) amplification (P=0.01). In common with CCND1/INT-2, EMS1 amplification was associated with increased risk of relapse in patients with lymph node-negative disease (P=0.028). In contrast, EMS1 and CCND1/INT-2 amplification appeared to confer different phenotypes in ER positive and negative tumours. A threefold increase in EMS1 copy number was associated with an apparent increased risk of relapse and death in patients with ER negative tumours, but was without effect in ER positive tumours. In contrast, CCND1/INT-2 amplification had no effect in the patients with ER negative tumours but was associated with early relapse in ER positive patients. Thus EMS1 amplification may identify subgroups of breast cancer patients with increased probability of relapse and death distinct from those identified by CCND1/INT-2 amplification.... [ABSTRACT FROM AUTHOR]

Background Overall survival is the optimal marker of treatment efficacy in randomized clinical trials (RCTs) but can take considerable time to mature. Progression-free survival (PFS) has served as an early surrogate of overall survival but is imperfect. Time to deterioration in quality of life (QOL) measures could be a surrogate for overall survival. Methods Phase 3 RCTs in solid malignancies that reported overall survival, PFS, and time to deterioration in QOL or physical function published between January 1, 2010, and June 30, 2022, were evaluated. Weighted regression analysis was used to assess the relationship between PFS, time to deterioration in QOL, and time to deterioration in physical function with overall survival. The coefficient of determination (R 2) was used to quantify surrogacy. Results In total, 138 phase 3 RCTs were included. Of these, 47 trials evaluated immune checkpoint inhibitors and 91 investigated non–immune checkpoint inhibitor agents. Time to deterioration in QOL (137 RCTs) and time to deterioration in physical function (75 RCTs) performed similarly to PFS as surrogates for overall survival (R 2 = 0.18 vs R 2 = 0.19 and R 2 = 0.10 vs R2 = 0.09, respectively). For immune checkpoint inhibitor studies, time to deterioration in physical function had a higher association with overall survival than with PFS (R 2 = 0.38 vs R2 = 0.19), and PFS and time to deterioration in physical function did not correlate with each other (R 2 = 0). When time to deterioration in physical function and PFS are used together, the coefficient of determination increased (R 2 = 0.57). Conclusions Time to deterioration in physical function appears to be an overall survival surrogate measure of particular importance for immune checkpoint inhibitor treatment efficacy. The combination of time to deterioration in physical function with PFS may enable better prediction of overall survival treatment benefit in RCTs of immune checkpoint inhibitors than either PFS or time to deterioration in physical function alone. [ABSTRACT FROM AUTHOR]

Aims: There is robust trial evidence for improved overall survival (OS) with immunotherapy in advanced solid organ malignancies. The real‐world long‐term survival data and the predictive variables are not yet known. Our aim was to evaluate factors associated with 3‐year and 5‐year OS for patients treated with immune checkpoint inhibitors (ICIs). Methods: We performed a retrospective study of patients who received ICIs as management of advanced solid organ malignancies in two tertiary Australian oncology centres from 2012–2017. Data pertaining to clinical characteristics, metastatic disease burden, immune‐related adverse events (IRAEs) and tumour responses were collected and their relationship to survival examined. Results: In this analysis of 264 patients, 202 (76.5%) had melanoma, 46 (17.4%) had non‐small cell lung cancer (NSCLC), 12 (4.5%) had renal cell carcinoma (RCC) and 4 (1.5%) had mesothelioma. The 5‐year OS rates were 42.1% in patients with melanoma, 19.6% with NSCLC, 75% with RCC, and none of the mesothelioma patients were alive at 5 years. In multivariate analysis, an ECOG score of 0 (Hazard ratio [HR] 0.39; 95% confidence interval [CI] 0.23–0.66; p < 0.001) and the occurrence of IRAE's of any grade (HR 0.61; 95% CI 0.37–0.95; p = 0.05) were associated with better 5‐year survival. The presence of bone metastases (HR 1.62; 95% CI 1.03–2.82; p = 0.05) and liver metastases (HR 1.76; 95% CI 1.07–2.89; p = 0.03) were associated with worse 5‐year survival. Conclusions: These results support the long‐term benefits of immunotherapy that in some patients, extend to at least 5 years. ECOG performance status of 0 and the occurrence of irAEs are associated with better long‐term survival. Survival is significantly influenced by metastatic site and cancer type. These predictive clinical correlates aid discussions and planning in the delivery of ICIs to patients. [ABSTRACT FROM AUTHOR]

• Over one-fifth of patients wait > 14 days for their EGFR mutation test results. • One-fifth of patients never receive EGFR tyrosine kinase inhibitor treatment. • Significant inter-country variability exists in patients receiving EGFR treatment. • Improvement in EGFR mutation testing turnaround times and treatment is needed. Epidermal growth factor receptor (EGFR) mutations (EGFR m) are common oncogene drivers in non-small cell lung cancer (NSCLC). This real-world study explored treatment patterns and time to receive EGFR m test results in patients with advanced EGFR m NSCLC. A cross-sectional medical chart review was completed May–August 2020 in Australia, Canada, Germany, Italy, South Korea, Taiwan, UK, and USA. Eligible patients had advanced NSCLC and a positive EGFR m test result January–December 2017. Data were abstracted from NSCLC diagnosis to end of follow-up (31 March 2020) or patient's death whichever occurred earlier. The index date was the date of EGFR m confirmation. 223 physicians provided data for 1,793 patients. Patients' mean age was 64.7 years, 54 % were male, 30.7 % had no history of smoking. Overall, 78 % of EGFR m test results were received ≤ 2 weeks after request (range of median 7–14 days across countries). Median time from advanced NSCLC diagnosis to EGFR m test result was 18 days (median range 10–22 days across countries). Over a third (37 %) of patients received a systemic treatment prior to EGFR m result; chemotherapy (25 %) and EGFR-TKI (15 %) were most commonly prescribed; post- EGFR test-result was EGFR-TKI (68 %); 80 % of patients initiated EGFR-TKI at any time point post-NSCLC diagnosis. Of those receiving a first-line EGFR-TKI post- EGFR m testing, 84 % received a TKI alone, 12 % in combination with chemotherapy, and 3 % with other treatments. Median time from first-line EGFR-TKI initiation post- EGFR m testing to first subsequent treatment was 19.8 months. Over one-fifth of patients wait >14 days for their EGFR m test results, affecting their likelihood of receiving first-line EGFR-TKI with 20 % of patients never receiving EGFR TKI treatment. There was significant inter-country variability in the proportion of patients receiving EGFR TKIs. Our study highlights the need to improve EGFR m testing turnaround times and treatment initiation across countries. [ABSTRACT FROM AUTHOR]

Background and objectives: Due to difficulties in identifying sufficient‐sized cohorts there remains uncertainty about prognostic and clinical differences that may be unique to asbestos‐related lung cancer (ARLC). In this study, we use the Helsinki Criteria to define a group of ex‐workers with lung cancer attributable to asbestos exposure and investigate differences that may exist. Methods: A total of 529 patients seeking workers' compensation for their lung cancer were assigned to either ARLC or the non‐ARLC based on parameters defined in the Helsinki Criteria. Clinical and survival details were collected and analyzed. Results: In our study population, ARLC patients were on average older (72.1 ± 7.8) than non‐ARLC patients (66.5 ± 10.2, P < 0.001) and were more likely to be diagnosed as a result of incidental findings or screening program (P < 0.001). The groups were similar in terms of clinical characteristics with the only difference being that plaques were more prevalent among ARLC patients (P < 0.001). Differences were observed for median overall survival (OS), ARLC (9 months) and non‐ARLC (13 months, P = 0.005), as well for treatment (P = 0.01). After adjusting for age, however, these differences disappeared. Conclusions: Age at diagnosis, pleural plaques, and asymptomatic presentation were the attributes that we identified as significantly different between asbestos‐related cancer and other lung cancers. In this cohort, ARLC patients were older diagnosis and with worse overall survival. [ABSTRACT FROM AUTHOR]

The article discusses a study that assessed the efficacy and safety of programmed cell death (PD) 1 inhibition with pembrolizumab in patients with advanced non-small-cell lung cancer enrolled in a phase 1 study. Study highlights include assessment of PD-ligand 1 expression in tumor samples via immunohistochemical analysis, common side effects that were attributed to pembrolizumab, and a diagram that shows enrollment and assignment to training group and validation group.

• Grade 3/4 and fatal imAEs were uncommon with durvalumab after CRT. • Pneumonitis and thyroid disorders were the most common imAEs with this regimen. • ImAEs typically occurred within 3 months of durvalumab initiation. • In general, imAEs were well managed with appropriate clinical intervention. • Time elapsed between RT and randomization did not impact imAE incidence or severity. Immune-mediated adverse events (imAEs), including all-cause immune-mediated pneumonitis, were reported in approximately 25% of patients in the placebo-controlled, phase III PACIFIC trial of durvalumab monotherapy (for up to 12 months) in patients with unresectable, stage III NSCLC and no disease progression after concurrent chemoradiotherapy; only 3.4% of patients experienced grade 3/4 imAEs. With broad application of the PACIFIC regimen (consolidation durvalumab after chemoradiotherapy), now standard-of-care in this setting, there is a need to better characterize the occurrence of imAEs with this regimen. We performed descriptive, post-hoc, exploratory analyses to characterize the occurrence of imAEs (pneumonitis and non-pneumonitis) in PACIFIC in terms of: incidence, severity, and timing; clinical management and outcomes; and associations between the occurrence of imAEs and (1) all-cause AEs and (2) baseline patient, disease, and treatment characteristics. Any-grade immune-mediated pneumonitis (9.4%) and non-pneumonitis imAEs (10.7%) occurred infrequently and were more common with durvalumab versus placebo. Grade 3/4 immune-mediated pneumonitis (1.9%) and non-pneumonitis imAEs (1.7%) were uncommon with durvalumab, as were fatal imAEs (0.8%; all pneumonitis). The most common non-pneumonitis imAEs with durvalumab were thyroid disorders, dermatitis/rash, and diarrhea/colitis. Dermatitis/rash had the shortest time to onset (from durvalumab initiation), followed by pneumonitis; dermatitis/rash had the longest time to resolution, followed by thyroid disorders. Most patients with immune-mediated pneumonitis (78.4%) and non-pneumonitis imAEs (56.3%) had these events occur ≤ 3 months after initiating durvalumab. ImAEs were well managed with administration of systemic corticosteroids, administration of endocrine replacement therapy, and interruption/discontinuation of durvalumab. Time elapsed from completion of prior radiotherapy to trial randomization (<14 vs. ≥ 14 days) did not impact either incidence or severity of imAEs. Durvalumab had a manageable safety profile broadly irrespective of whether patients experienced imAEs. The risk of imAEs should not deter use of the PACIFIC regimen in eligible patients, as these events are generally well managed through appropriate clinical intervention. [ABSTRACT FROM AUTHOR]

Overall survival (OS) results from randomized control trials (RCT) provide the strongest evidence for efficacy of anti-cancer treatments but can take a considerable amount of time to mature. Progression free survival (PFS) and objective response rate (ORR) are used as an early surrogate of OS treatment effect however their validity remains unclear. Our study aims to comprehensively evaluate ORR and PFS as surrogates for OS treatment effect across tumor groups and treatment types. Phase 3 RCTs in solid malignancies that reported OS/PFS and ORR published between 1st of January 2010 and 30th of June 2022 were evaluated. The relationship of surrogate endpoints and OS treatment effect was assessed via weighted linear regression. The coefficient of determination (R2) quantified the fit of the regression model. 675 phase 3 RCT comprising of 350 112 patients were analysed. ORR (R2 of 0.10) and PFS (R2 of 0.38) were poor surrogate markers of OS treatment effect. The strength of surrogacy differed within treatment and tumour groups. PFS had the highest R2 for chemotherapy (0.56) and lowest for targeted therapy (0.40). PFS had the highest level of surrogacy for melanoma (R2 = 0.72) and pancreatic cancer (R2 = 0.70) compared to other tumour groups. Importantly ORR and PFS were also poorly correlated to each other (R2 = 0.33). ORR and PFS were poor trial-level surrogate markers of OS. The surrogacy performance of ORR and PFS differed by treatment and malignancy sub-type. • ORR and PFS are not strong surrogates of OS treatment effect. • Surrogacy of ORR and PFS for OS differs based on treatment and tumor. • surrogacy of ORR and PFS for OS treatment effect was highest for chemotherapy. • PFS was a better surrogate of OS treatment for melanoma and pancreatic cancer. [ABSTRACT FROM AUTHOR]

• PD-L1 as a biomarker in EGFR-mutant lung adenocarcinoma is controversial. • High baseline PD-L1 expression was associated with shorter PFS and OS to EGFR TKI. • PD-L1 expression was the most significant prognostic biomarker. • Post-progression high PD-L1 was not associated with poor outcomes. Predictive biomarkers for poor response to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) is an area of ongoing research. This multicentre retrospective study sought to determine the impact of programmed death-ligand 1 (PD-L1) tumour proportional score (TPS) on outcome in EGFR TKI treated patients. Patients with Stage IIIB/IV lung adenocarcinoma harbouring a sensitising EGFR mutation treated with first-line TKI at five metropolitan hospitals were included. PD-L1 TPS was determined using the Ventana anti-PD-L1 (SP263) assay. High PD-L1 expression was defined as TPS ≥ 50 %. Determinants of progression and survival hazards were modelled using Cox regression. A total of 186 patients were included. Mean age was 67 years, 66 % were female and 54 % were Asian. Patients with high PD-L1 expression (n = 23; 12 %) had significantly shorter progression free survival (6.6 vs 13.0 months, hazard ratio (HR) 2.6 95 % CI 1.6–4.2, p < 0.0001) and overall survival (11.5 vs 32.9 months, HR 3.3, 95 % CI 1.9–5.7, p < 0.0001) compared to patients with PD-L1 low/negative tumours. This remained significant in multivariate analyses. High PD-L1 in post-TKI progression biopsies was not associated with poorer survival. In this large, real-world cohort of EGFR- mutant lung adenocarcinoma patients, high PD-L1 expression was associated with early resistance to 1st generation EGFR TKIs and shorter survival, regardless of ethnicity. [ABSTRACT FROM AUTHOR]

• Trial enrollment was not stratified for variables related to mandatory prior CRT. • Clinical outcomes were assessed in subgroups defined by CRT-related variables. • As in the ITT population, PFS, OS and TTDM favored durvalumab use in all subgroups. • Durvalumab had a manageable safety profile irrespective of CRT-related variables. • Imbalances in baseline factors and subgroup sizes prevent robust conclusions. The PACIFIC trial demonstrated that durvalumab significantly improved progression-free and overall survival (PFS/OS), versus placebo, in patients with Stage III NSCLC and stable or responding disease following concurrent, platinum-based chemoradiotherapy (CRT). A range of CT and RT regimens were permitted, and used, in the trial. We report post-hoc, exploratory analyses of clinical outcomes from PACIFIC according to CRT-related variables. Patients were randomized 2:1 (1–42 days post-CRT) to up to 12 months durvalumab (10 mg/kg intravenously every 2 weeks) or placebo. Efficacy and safety were analyzed in patient subgroups defined by the following baseline variables: platinum-based CT (cisplatin/carboplatin); vinorelbine, etoposide, or taxane-based CT (all yes/no); total RT dose (<60 Gy/60–66 Gy/>66 Gy); time from last RT dose to randomization (<14 days/≥14 days); and use of pre-CRT induction CT (yes/no). Treatment effects for time-to-event endpoints were estimated by hazard ratios (HRs) from unstratified Cox-proportional-hazards models. Overall, 713 patients were randomized, of whom 709 received treatment in either the durvalumab (n/N = 473/476) or placebo arms (n/N = 236/237). Durvalumab improved PFS, versus placebo, across all subgroups (median follow up, 14.5 months; HR range, 0.34–0.63). Durvalumab improved OS across most subgroups (median follow up, 25.2 months; HR range, 0.35–0.86); however, the 95 % confidence interval (CI) of the estimated treatment effect crossed one for the subgroups of patients who received induction CT (HR, 0.78 [95 % CI, 0.51–1.20]); carboplatin (0.86 [0.60–1.23]); vinorelbine (0.79 [0.49–1.27]); and taxane-based CT (0.73 [0.51–1.04]); and patients who were randomized ≥14 days post-RT (0.81 [0.62–1.06]). Safety was broadly similar across the CRT subgroups. Durvalumab prolonged PFS and OS irrespective of treatment variables related to prior CRT to which patients with Stage III NSCLC had previously stabilized or responded. Limited patient numbers and imbalances in baseline factors in each subgroup preclude robust conclusions. [ABSTRACT FROM AUTHOR]

Background: Pembrolizumab plus pemetrexed-platinum led to superior overall survival and progression-free survival, and a higher proportion of patients with a confirmed complete or partial response over placebo plus pemetrexed-platinum in the KEYNOTE-189 study. We aimed to evaluate prespecified exploratory patient-reported outcomes (PROs) in patients in KEYNOTE-189.Methods: In the multicentre, double-blind, randomised, placebo-controlled, phase 3 KEYNOTE-189 study done at 126 cancer centres in 16 countries, eligible patients aged 18 years or older with histologically or cytologically confirmed metastatic non-squamous non-small-cell lung cancer without sensitising EGFR or ALK alterations, measurable disease as per Response Evaluation Criteria in Solid Tumors (version 1.1), and an Eastern Cooperative Oncology Group performance status of 0 or 1 were enrolled. Patients were randomly assigned (2:1) to receive intravenous pembrolizumab (200 mg) or saline placebo every 3 weeks for up to 2 years (35 cycles); all patients received four cycles of intravenous pemetrexed (500 mg/m2) with carboplatin (5 mg/mL per min) or cisplatin (75 mg/m2; investigator's choice) every 3 weeks for four cycles, followed by pemetrexed maintenance therapy every 3 weeks. Permuted block randomisation (block size six) was done with an interactive voice-response system and stratified by PD-L1 expression, choice of platinum, and smoking status. Patients, investigators, and other study personnel were unaware of treatment assignment. The European Organisation for Research and Treatment of Cancer Quality-of-Life Questionnaire-Core 30 (QLQ-C30) and Lung Cancer 13 (QLQ-LC13) were administered at cycles 1-5, every three cycles thereafter during year 1, and every four cycles during years 2-3. The primary endpoints (overall survival and progression-free survival) have been published previously. Key PRO endpoints were change from baseline to week 12 (during chemotherapy) and week 21 (following chemotherapy) in QLQ-C30 global health status/quality of life (GHS/QOL) score, and time to deterioration in cough, chest pain, or dyspnoea. PROs were analysed in all randomly assigned patients who received at least one dose of study medication and who completed at least one PRO assessment, and the results are provided with two-sided, nominal p values. This ongoing study is registered with ClinicalTrials.gov, number NCT02578680.Findings: Between Feb 26, 2016, and March 6, 2017, 616 patients were enrolled; median follow-up was 10·5 months (range 0·2-20·4) as of data cutoff on Nov 8, 2017. 402 (99%) of 405 patients in the pembrolizumab plus pemetrexed-platinum group and 200 (99%) of 202 patients in the placebo plus pemetrexed-platinum-treated group completed at least one PRO assessment. At baseline, 359 (89%) of 402 patients in the pembrolizumab plus pemetrexed-platinum group and 180 (90%) of 200 in the placebo plus pemetrexed-platinum group were compliant with QLQ-C30; at week 12, 319 (90%) of 354 and 149 (89%) of 167 patients were compliant, respectively; and at week 21, 249 (76%) of 326 and 91 (64%) of 143 patients were compliant, respectively. From baseline to week 12, GHS/QOL scores were maintained with both pembrolizumab plus pemetrexed-platinum (least-squares mean change: 1·0 point [95% CI -1·3 to 3·2] increase) and placebo plus pemetrexed-platinum (-2·6 points [-5·8 to 0·5] decrease; between-group difference: 3·6 points [-0·1 to 7·2]; p=0·053). From baseline to week 21, GHS/QOL scores were better maintained with pembrolizumab plus pemetrexed-platinum (least-squares mean change: 1·3 points [95% CI -1·2 to 3·6] increase) than with placebo plus pemetrexed-platinum (-4·0 points [-7·7 to -0·3] decrease; between-group difference: 5·3 points [1·1 to 9·5]; p=0·014). Median time to deterioration in cough, chest pain, or dyspnoea was not reached (95% CI 10·2 months to not reached) with pembrolizumab plus pemetrexed-platinum, and was 7·0 months (4·8 months to not reached) with placebo plus pemetrexed-platinum (hazard ratio 0·81 [95% CI 0·60-1·09], p=0·16).Interpretation: The addition of pembrolizumab to standard chemotherapy maintained GHS/QOL, with improved GHS/QOL scores at week 21 in the pembrolizumab plus chemotherapy group compared with the placebo plus chemotherapy group. These data further support use of pembrolizumab plus pemetrexed-platinum as first-line therapy for patients with metastatic non-squamous non-small-cell lung cancer.Funding: Merck Sharp & Dohme. [ABSTRACT FROM AUTHOR]

Context: Physical activity for women with early-stage breast cancer is well recognized for managing cancer-related symptoms and improving quality of life. While typically excluded from interventions, women with metastatic breast cancer may also benefit from physical activity.Objective: To 1) determine the safety and feasibility of a physical activity program for women with metastatic breast cancer and 2) explore the efficacy of the program.Methods: Fourteen women with metastatic breast cancer were randomized to either a control group or an 8-week home-based physical activity intervention comprising twice weekly supervised resistance training and an unsupervized walking program.Results: The recruitment rate was 93%. Adherence to the resistance and walking components of the program was 100% and 25%, respectively. No adverse events were reported. When mean change scores from baseline to postintervention were compared, trends in favor of the exercise group over the control group were observed for the Functional Assessment of Chronic Illness Therapy-Fatigue score (+5.6 ± 3.2 vs. -1.8 ± 3.9, respectively), VO2max (+1.6 ml/kg/minute ±1.8 mL/kg/minute vs. -0.2 mL/kg/minute ±0.1 mL/kg/minute, respectively) and six-minute walk test (+40 m ± 23 m vs. -46 m ± 56 m, respectively).Conclusion: A partially supervised home-based physical activity program for women with metastatic breast cancer is feasible and safe. The dose of the resistance training component was well tolerated and achievable in this population. In contrast, adherence and compliance to the walking program were poor. Preliminary data suggest a physical activity program, comprising predominantly resistance training, may lead to improvements in physical capacity and may help women to live well with their disease. [ABSTRACT FROM AUTHOR]

Stage III non–small cell lung cancer (NSCLC) makes up a third of all NSCLC cases and is potentially curable. Despite this 5‐year survival rates remain between 15% and 20% with chemoradiation treatment alone given with curative intent. With the recent exciting breakthroughs in immunotherapy use (durvalumab) for stage III NSCLC, further improvements in patient survival can be expected. Most patients with stage III NSCLC present initially to their general practitioner (GP). The recommended time from GP referral to first specialist appointment is less than 14 days with treatment initiated within 42 days. Our review found that there is a shortfall in meeting these recommendations, however a number of initiatives have been established in Australia to improve timely and accurate diagnosis and treatment patterns. The lung cancer multidisciplinary team (MDT) is critical to consistency of evidence‐based diagnosis and treatment and can improve patient survival. We aimed to review current patterns of care and clinical practice recommendations for stage III NSCLC across Australia and identify opportunities to improve practice in referral, diagnosis and treatment pathways. [ABSTRACT FROM AUTHOR]

Background: HER2-positive breast cancers usually contain large amounts of T-cell infiltrate. We hypothesised that trastuzumab resistance in HER2-positive breast cancer could be mediated by immune mechanisms. We assessed the safety and anti-tumour activity of pembrolizumab, a programmed cell death protein 1 (PD-1) inhibitor, added to trastuzumab in trastuzumab-resistant, advanced HER2-positive breast cancer.Methods: We did this single-arm, multicentre, phase 1b-2 trial in 11 centres based in five countries. Eligible participants were women aged 18 years or older, who had advanced, histologically confirmed, HER2-positive breast cancer; documented progression during previous trastuzumab-based therapy; an Eastern Cooperative Oncology Group performance status of 0 or 1; and a formalin-fixed, paraffin-embedded metastatic tumour biopsy for central assessment of programmed cell death 1 ligand 1 (PD-L1) status. In phase 1b, we enrolled patients with PD-L1-positive tumours in a 3 + 3 dose-escalation of intravenous pembrolizumab (2 mg/kg and 10 mg/kg, every 3 weeks) plus 6 mg/kg of intravenous trastuzumab. The primary endpoint of the phase 1b study was the incidence of dose-limiting toxicity and recommended phase 2 dose; however, a protocol amendment on Aug 28, 2015, stipulated a flat dose of pembrolizumab of 200 mg every 3 weeks in all Merck-sponsored trials. In phase 2, patients with PD-L1-positive and PD-L1-negative tumours were enrolled in parallel cohorts and received the flat dose of pembrolizumab plus standard trastuzumab. The primary endpoint of the phase 2 study was the proportion of PD-L1-positive patients achieving an objective response. This trial is registered in ClinicalTrials.gov, number NCT02129556, and with EudraCT, number 2013-004770-10, and is closed.Findings: Between Feb 2, 2015, and April 5, 2017, six patients were enrolled in phase 1b (n=3 received 2 mg/kg pembrolizumab, n=3 received 10 mg/kg pembrolizumab) and 52 patients in phase 2 (n=40 had PD-L1-positive tumours, n=12 had PD-L1-negative tumours). The data cutoff for this analysis was Aug 7, 2017. During phase 1b, there were no dose-limiting toxicities in the dose cohorts tested. Median follow-up for the phase 2 cohort was 13·6 months (IQR 11·6-18·4) for patients with PD-L1-positive tumours, and 12·2 months (7·9-12·2) for patients with PD-L1-negative tumours. Six (15%, 90% CI 7-29) of 40 PD-L1-positive patients achieved an objective response. There were no objective responders among the PD-L1-negative patients. The most common treatment-related adverse event of any grade was fatigue (12 [21%] of 58 patients). Grade 3-5 adverse events occurred in 29 (50%) of patients, treatment-related grade 3-5 adverse events occurred in 17 (29%), and serious adverse events occurred in 29 (50%) patients. The most commonly occurring serious adverse events were dyspnoea (n=3 [5%]), pneumonitis (n=3 [5%]), pericardial effusion (n=2 [3%]), and upper respiratory infection (n=2 [3%]). There was one treatment-related death due to Lambert-Eaton syndrome in a PD-L1-negative patient during phase 2.Interpretation: Pembrolizumab plus trastuzumab was safe and showed activity and durable clinical benefit in patients with PD-L1-positive, trastuzumab-resistant, advanced, HER2-positive breast cancer. Further studies in this breast cancer subtype should focus on a PD-L1-positive population and be done in less heavily pretreated patients.Funding: Merck, International Breast Cancer Study Group. [ABSTRACT FROM AUTHOR]

Abstract: Resistance to endocrine therapy is a significant therapeutic challenge in the treatment of women with hormone receptor positive (HR+), human epidermal growth factor receptor 2 negative (HER2–) advanced breast cancer. Cyclin‐dependent kinase (CDK)4/6 inhibitors in combination with endocrine therapy have been shown to improve progression free survival, overall response rate and clinical benefit rate in women with HR+ HER2– metastatic breast cancer compared with endocrine therapy alone. This review examines the clinical evidence to support the use of CDK4/6 inhibitors in first and second line settings. Practical guidance is provided for the use of CDK4/6 inhibitors, including tolerability data, monitoring requirements and management of key toxicities for each of the available agents. [ABSTRACT FROM AUTHOR]

Abstract: Cyclin‐dependent kinase (CDK4/6) inhibitors in combination with endocrine therapy are currently the optimal first line treatment for hormone receptor (HR) positive, human epidermal growth factor receptor 2 (HER2) non‐amplified metastatic breast cancer (MBC). However, not all patients benefit from this treatment and all patients will inevitably progress. Identifying therapeutic strategies in this setting is therefore of immediate clinical importance. We present an overview of the mechanisms of resistance to CDK4/6 inhibitors and review potential biomarkers that may guide therapy selection. We also discuss the use of CDK4/6 inhibitors in the context of non‐HR‐positive/HER2‐non‐amplified breast cancer and in combination with therapies other than endocrine therapy. [ABSTRACT FROM AUTHOR]

Background: In the phase 3 KEYNOTE-024 trial, treatment with pembrolizumab conferred longer progression-free survival than did platinum-based therapy in patients with treatment-naive, advanced non-small-cell lung cancer (NSCLC) with a programmed cell death-ligand 1 (PD-L1) tumour proportion score of 50% or greater (PD-L1-positive). Here we report the prespecified exploratory endpoint of pembrolizumab versus chemotherapy on patient-reported outcomes (PROs).Methods: In this multicentre, international, randomised, open-label, phase 3 trial, we recruited patients with treatment-naive, stage IV NSCLC in 102 sites in 16 countries. Eligible patients had measurable disease (per RECIST version 1.1) and an Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1. Patients were randomly assigned (1:1) via an interactive voice response system and integrated web response system to receive either pembrolizumab 200 mg every 3 weeks (35 cycles) or investigator-choice platinum-doublet chemotherapy (4-6 cycles or until documented disease progression or unacceptable toxicity). Randomisation was stratified according to geography, ECOG performance status, and histology. PROs were assessed at day 1 of cycles 1-3, every 9 weeks thereafter, at the treatment discontinuation visit, and at the 30-day safety assessment visit using the European Organisation for the Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 items (QLQ-C30), the EORTC Quality of Life Questionnaire Lung Cancer 13 items (QLQ-LC13), and the European Quality of Life 5 Dimensions-3 Level (EQ-5D-3L) questionnaire. The key exploratory PRO endpoints (analysed for all patients who received at least one dose of study treatment and completed at least one PRO instrument at at least one timepoint) were baseline-to-week-15 change in the QLQ-C30 global health status (GHS)/quality-of-life (QOL) score and time to deterioration of the composite of cough, chest pain, and dyspnoea in the QLQ-LC13. This study is registered with ClinicalTrials.gov, number NCT02142738, and is ongoing but no longer enrolling patients.Findings: Between Sept 19, 2014, and Oct 29, 2015, 305 patients were randomly assigned to pembrolizumab (n=154) or chemotherapy (n=151). Three patients in each group did not complete any PRO instruments at any timepoints, and so 299 patients were included in the full analysis set. Of these patients, one in each group did not complete any PRO instruments before week 15, and so were not included in analyses of change from baseline to week 15. PRO compliance was greater than 90% at baseline and approximately 80% at week 15 for both groups. Least-squares mean baseline-to-week-15 change in QLQ-C30 GHS/QOL score was 6·9 (95% CI 3·3 to 10·6) for pembrolizumab and -0·9 (-4·8 to 3·0) for chemotherapy, for a difference of 7·8 (2·9 to 12·8; two-sided nominal p=0·0020). Fewer pembrolizumab-treated patients had deterioration in the QLQ-LC13 composite endpoint than did chemotherapy-treated patients (46 [31%] of 151 patients vs 58 [39%] of 148 patients). Time to deterioration was longer with pembrolizumab than with chemotherapy (median not reached [95% CI 8·5 to not reached] vs 5·0 months [3·6 to not reached]; hazard ratio 0·66, 95% CI 0·44-0·97; two-sided nominal p=0·029).Interpretation: Pembrolizumab improves or maintains health-related QOL compared with that for chemotherapy, and might represent a new first-line standard of care for PD-L1-expressing, advanced NSCLC.Funding: Merck & Co. [ABSTRACT FROM AUTHOR]

Aims: 2 dimensional (2D) strain analysis detects subclinical left ventricular (LV) systolic dysfunction. Our aim was to evaluate changes in LV systolic and diastolic function in breast cancer patients early after anthracycline chemotherapy, and to identify predisposing factors. Methods and results: 140 patients were assessed by detailed echocardiography before and within seven days post treatment. LV ejection fraction (LVEF), global longitudinal strain (GLS), strain rate and radial and circumferential strain were assessed. Additionally, left atrial volumes and LV diastolic parameters were evaluated. LVEF although reduced after treatment, remained within the normal range (60±3% vs. 59±3%, p = 0.04). Triplane GLS was significantly reduced after treatment (-20.0±1.6% vs. -19.1±1.8%, p<0.001). Subclinical LV dysfunction (>11% reduction in GLS compared to before therapy) occurred in 22% (29/135). Impaired diastolic function grade significantly increased from 46% to 57% (p<0.001) after treatment. Furthermore, diastolic dysfunction was more common in the subgroup group with reduced systolic GLS compared to those without changes in GLS (30% vs. 11%; p = 0.04). No risk factors or clinical parameters were associated with the development of subclinical LV dysfunction; however the percentage change in early diastolic strain rate and the E velocity were independent predictors of >11% reduction in GLS. Conclusion: Twenty two percent of patients had subclinical LV dysfunction by GLS, whilst none had cardiotoxicity defined by LVEF, demonstrating that GLS is more sensitive for detection of subclinical LV systolic dysfunction immediately after anthracycline therapy. Diastolic dysfunction increased, particularly in the group with reduced GLS, demonstrating the close pathophysiological relationship between systolic and diastolic function. [ABSTRACT FROM AUTHOR]

Background: Pembrolizumab is a humanized monoclonal antibody against programmed death 1 (PD-1) that has antitumor activity in advanced non-small-cell lung cancer (NSCLC), with increased activity in tumors that express programmed death ligand 1 (PD-L1).Methods: In this open-label, phase 3 trial, we randomly assigned 305 patients who had previously untreated advanced NSCLC with PD-L1 expression on at least 50% of tumor cells and no sensitizing mutation of the epidermal growth factor receptor gene or translocation of the anaplastic lymphoma kinase gene to receive either pembrolizumab (at a fixed dose of 200 mg every 3 weeks) or the investigator's choice of platinum-based chemotherapy. Crossover from the chemotherapy group to the pembrolizumab group was permitted in the event of disease progression. The primary end point, progression-free survival, was assessed by means of blinded, independent, central radiologic review. Secondary end points were overall survival, objective response rate, and safety.Results: Median progression-free survival was 10.3 months (95% confidence interval [CI], 6.7 to not reached) in the pembrolizumab group versus 6.0 months (95% CI, 4.2 to 6.2) in the chemotherapy group (hazard ratio for disease progression or death, 0.50; 95% CI, 0.37 to 0.68; P<0.001). The estimated rate of overall survival at 6 months was 80.2% in the pembrolizumab group versus 72.4% in the chemotherapy group (hazard ratio for death, 0.60; 95% CI, 0.41 to 0.89; P=0.005). The response rate was higher in the pembrolizumab group than in the chemotherapy group (44.8% vs. 27.8%), the median duration of response was longer (not reached [range, 1.9+ to 14.5+ months] vs. 6.3 months [range, 2.1+ to 12.6+]), and treatment-related adverse events of any grade were less frequent (occurring in 73.4% vs. 90.0% of patients), as were grade 3, 4, or 5 treatment-related adverse events (26.6% vs. 53.3%).Conclusions: In patients with advanced NSCLC and PD-L1 expression on at least 50% of tumor cells, pembrolizumab was associated with significantly longer progression-free and overall survival and with fewer adverse events than was platinum-based chemotherapy. (Funded by Merck; KEYNOTE-024 ClinicalTrials.gov number, NCT02142738 .). [ABSTRACT FROM AUTHOR]

Abstract: Aim: Anthracycline agents are undermined by their cardiotoxicity. As life expectancy following treatment is greatly improved, techniques that ensure early detection and timely management of cardiotoxicity are essential. The aim of the present study was to evaluate left ventricular (LV) systolic function with LV ejection fraction (LVEF) and two-dimensional myocardial strain up to 12months after anthracycline chemotherapy, specifically in HER2/neu negative breast cancer patients. Methods: Seventy-eight consecutive anthracycline naïve breast cancer patients were studied before and immediately after anthracycline chemotherapy. Fifty HER2/neu negative patients were studied over 12months with serial echocardiograms at four time points. All patients were treated with standard regimens containing anthracyclines. Results: Global systolic strain was significantly reduced immediately after, and 6months after anthracyclines (−19.0±2.3% to −17.5±2.3% (P <0.001) and −18.2±2.2% (P =0.01) respectively). A non-uniform reduction in strain was observed each time with relative sparing of the LV apex. LVEF remained largely unchanged at both time points. Global strain normalised by 12months in the majority of patients. Persistently reduced strain was observed in 16% (n =8); these patients had a greater reduction in strain at 6months (⩽−17.2%), and had received higher cumulative anthracycline doses. Conclusion: Myocardial strain imaging is more sensitive than LVEF for the early detection and intermediate term monitoring of LV systolic function following anthracycline chemotherapy in HER2/neu negative breast cancer patients, and may aid in the development of improved monitoring protocols. [Copyright &y& Elsevier]

Background: Chronic inflammation has been recognized to foster tumour development. Whether chemotherapy can be used to neutralize chronic inflammation is unclear. Methods: We evaluated baseline and nadir neutrophils in 111 patients (pts.) with non-small cell lung cancer (NSCLC) and 118 pts. with ovarian cancer (OC) treated with chemotherapy administered with dose-individualization to achieve nadir neutropenia of 1.5. We used predefined baseline neutrophil cut-offs 4.5 × 109/L (NSCLC) and 3.9 × 109/L (OC). Results: Absence of chemotherapy-induced nadir neutropenia (CTCAE grade 0, neutrophils ≥ LLN) was seen in 23% of OC and 25% of NSCLC pts. Absence of nadir neutropenia was associated with decreased overall survival (OS) compared with presence (>grade 0) of neutropenia (9 vs. 14 months, P = 0.004 for NSCLC and 23 vs. 56 months; P = 0.01 for OC). Obtaining grade 3/4 neutropenia did not improve survival compared with grade 1/2 neutropenia. In multivariate analyses, baseline neutrophils ≥4.5 × 109/L (HR: 2.0; 95% CI: 1.11-3.44;P = 0.02) and absence of nadir neutropenia (HR: 1.6; 95% CI: 1.02-2.65;P = 0.04) for NSCLC and absence of nadir neutropenia (HR: 1.7; 95% CI: 1.04;2.93;P = 0.04) for OC were independently associated with short OS. Three prognostic neutrophil index (NI) groups were defined. Favourable NI: low baseline neutrophils and presence of nadir neutropenia (>grade 0), Intermediate NI: elevated baseline neutrophils and presence of nadir neutropenia (>grade 0), and Poor NI: elevated baseline neutrophils and absence of nadir neutropenia (grade 0). For NSCLC patients, the median OS was 18.0, 13.4, and 8.8 months for favourable, intermediate and poor NI, respectively (fav vs. poor P = 0.002; fav vs. intermed P=0.04; and intermed vs. poor P = 0.03). For OC patients, median OS was 69, 52 and 23 months for favourable, intermediate and poor NI, respectively (fav vs. poor P = 0.03; fav vs. intermed P = 0.3; and intermed vs. poor P = 0.02). Interestingly, survival rates in the intermediate NI groups indicated that individualised dose of chemotherapy to induce neutropenia may partly overcome the negative impact of elevated baseline neutrophils. Conclusions: A neutrophil index comprising elevated baseline neutrophils and absence of neutropenia identified a high risk group of NSCLC and ovarian cancer patients with only modest effect of chemotherapy. New treatment options for this subset of patients are required. [ABSTRACT FROM AUTHOR]

Abstract: Objective: Poor prognosis is difficult to impart, particularly across a cultural divide. This study compared prognostic communication with immigrants (with and without interpreters) versus native-born patients in audio-taped oncology consultations. Methods: Ten oncologists, 78 patients (31 Australian-born, 47 immigrants) and 115 family members participated. The first two consultations after diagnosis of incurable disease were audiotaped, transcribed and coded. 142 consultations were included in the analysis. Results: Fifty percent of doctor and 59% of patient prognostic speech units were not interpreted or interpreted non-equivalently when an interpreter was present. Immigrant status predicted few prognostic facts, and oncologist characteristics no prognostic facts, disclosed. Oncologists were significantly less likely to convey hope to immigrants (p =0.0004), and more likely to use medical jargon (p =0.009) than with Australian-born patients. Incurable disease status and a limited life span were commonly acknowledged, generally with no timeframe provided. Physical issues were discussed more commonly than emotional aspects. Conclusions: While culture did not appear to influence doctor speech, interpreters filtered or blocked much prognostic communication. Practice implications: Initiatives to empower all patients to attain needed information, optimise communication when an interpreter is present and train cancer health professionals in culturally appropriate care, are urgently required. [Copyright &y& Elsevier]

A 45-year-old female breast cancer patient developed heart failure during adjuvant trastuzumab therapy. Her initial left ventricular ejection fraction (LVEF) was 39% and corresponding global longitudinal and circumferential systolic strain measurements were also significantly reduced. Trastuzumab was ceased and supportive cardiac therapy commenced. The ensuing LVEF and systolic strain measurements showed consistent improvement so that trastuzumab was recommenced (while supportive cardiac therapy continued). At this point, reduced circumferential systolic strain with preserved LVEF was observed. Subsequent echocardiograms revealed further reductions in circumferential and longitudinal systolic strain without reductions in LVEF. (Echocardiography 2012;29:E137-E140) [ABSTRACT FROM AUTHOR]

Objective: Immigrants report challenges communicating with their health team. This study compared oncology consultations of immigrants with and without interpreters vs Anglo-Australian patients. Methods: Patients with newly diagnosed incurable cancer who had immigrated from Arabic, Chinese or Greek speaking countries or were Anglo-Australian, and family members, were recruited from 10 medical oncologists in 9 hospitals. Two consultations from each patient were audio-taped, transcribed, translated into English and coded. Results: Seventy-eight patients (47 immigrant and 31 Anglo-Australian) and 115 family members (77 immigrant and 38 Anglo Australian) participated in 141 audio-taped consultations. Doctors spoke less to immigrants with interpreters than to Anglo-Australians (1443 vs. 2246 words, p =0.0001), spent proportionally less time on cancer related issues (p =0.005) and summarising and informing (p ≤0.003) and more time on other medical issues (p =0.0008) and directly advising (p =0.0008). Immigrants with interpreters gave more high intensity cues (10.4 vs 7.4). Twenty percent of cues were not interpreted. Doctors tended to delay responses to or ignore more immigrant than Anglo-Australian cues (13% vs 5%, p =0.06). Conclusions: Immigrant cancer patients with interpreters experience different interactions with their doctors than Anglo-Australians, which may compromise their well-being and decisions. Practice implications: Guidelines and proven training programmes are needed to improve communication with immigrant patients, particularly those with interpreters. [Copyright &y& Elsevier]

Refinements to conventional treatment and the development of new therapies have led to significant improvements in cancer survival. Yet, many frontline cancer treatments continue to be hindered by their significant side effects, amongst which cardiotoxicity is particularly important. Therefore, the focus of cancer management has changed; treatment is no longer aimed solely at overcoming malignancy, but emphasises early identification and treatment of potential side effects. In this regard, the cardiotoxic potential of certain anticancer agents mandate close monitoring of cardiac function, and the method of choice for monitoring is transthoracic echocardiography. Whilst this method has its limitations, a newer echocardiographic technique called myocardial strain imaging has the potential to detect early sub-clinical changes in cardiac function due to cardiotoxicity. Strain analysis has been the subject of several recent studies to evaluate its potential in monitoring cardiotoxicity, and this article reviews the recent literature and explores the potential role of myocardial strain imaging in cancer management and avenues for future research. [ABSTRACT FROM AUTHOR]

Background: Chronic inflammation has been recognized to foster tumour development. Whether chemotherapy can be used to neutralize chronic inflammation is unclear.Methods: We evaluated baseline and nadir neutrophils in 111 patients (pts.) with non-small cell lung cancer (NSCLC) and 118 pts. with ovarian cancer (OC) treated with chemotherapy administered with dose-individualization to achieve nadir neutropenia of 1.5. We used predefined baseline neutrophil cut-offs 4.5 × 109/L (NSCLC) and 3.9 × 109/L (OC).Results: Absence of chemotherapy-induced nadir neutropenia (CTCAE grade 0, neutrophils ≥ LLN) was seen in 23% of OC and 25% of NSCLC pts. Absence of nadir neutropenia was associated with decreased overall survival (OS) compared with presence (>grade 0) of neutropenia (9 vs. 14 months, P=0.004 for NSCLC and 23 vs. 56 months; P=0.01 for OC). Obtaining grade 3/4 neutropenia did not improve survival compared with grade 1/2 neutropenia. In multivariate analyses, baseline neutrophils ≥ 4.5 × 109/L (HR: 2.0; 95% CI: 1.11-3.44;P = 0.02) and absence of nadir neutropenia (HR: 1.6; 95% CI: 1.02-2.65;P = 0.04) for NSCLC and absence of nadir neutropenia (HR: 1.7; 95% CI: 1.04;2.93;P = 0.04) for OC were independently associated with short OS.Conclusions: A neutrophil index comprising elevated baseline neutrophils and absence of neutropenia identified a high risk group of NSCLC and ovarian cancer patients with only modest effect of chemotherapy. New treatment options for this subset of patients are required. [ABSTRACT FROM AUTHOR]