Systemic Anticancer Treatment Research Articles

1521P - Evolving concurrent integration of oncology and palliative care at an ESMO designated center over a decade

Background: Streamlining oncology (Onc) and specialist palliative care (SPC) into integrated patient (pt) care is increasingly a gold standard of optimized cancer care. The ways that integrated Onc/SPC manifests in clinical practice may change over time. Little is known about factors that drive evolution in integrated care practices. Methods: From a pt’s first appointment with outpatient SPC, all visits were chronologically color coded for Onc, SPC, and Neutral (e.g. emergency) or joint visits (Onc/SPC same day). Visual Graphic Analysis revealed 4 patterns of integration (Onc only; SPC only; CONCurrent: permanent exchange of Onc and SPC, ≥5 switches, joint visits; SEGmented: alternating periods of Onc or SPC, <4 switches), independent researchers approved reliability of patterns definitions. Data from 2006-2009 (presented 34-ESMO 2009) were compared with 2016-2017. Explanatory factors for patterns evolution were derived from multi-professional, consensual discussion reviewing descriptive statistics (e.g. impact of inpt admission on patterns, pattern stability over 3 months intervals, anticancer treatment administered by SPC, pt characteristics) and further explored in the data. Results: 345 pts from 2006-09 and 64 from 2016 met eligibility criteria and were included. CONC occurred in 18% in 2006-09 and 45% in 2016 (Χ2 (1, N = 409) = 22.66, p < .001)], and 14% vs 50% remained in the CONC pattern comparing 3 months intervals. Elimination of inpt visits left 3/4 of patterns unchanged. A double-boarded Onc/SPC physician saw 94% of pts in the 2016 sample and prescribed systemic anticancer treatment in > 1/3 of these visits, 77% of these pts were in the CONC Pattern. Joint Onc/SPC visits were increasing over time, also (bi-)weekly alternating visits by Onc and SPC (double-boarded). Pts of CONC had complex and high needs for palliative interventions, were in phase I studies, or refused standard anticancer treatment, but accepted later. Conclusions: Concurrent Onc/SPC is an increasing and consistent pattern, not explained by mere bed availability. Prescribing anticancer therapy by a double-boarded physician may foster integration. Further research may determine how CONC affects pt outcomes and the influence of pt and physicians’ characteristics. Legal entity responsible for the study: Cantonal Hospital St.Gallen. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.

PCN219 - CHARACTERISTICS AND TREATMENT PATTERNS IN PATIENTS WITH LOCALLY ADVANCED AND METASTATIC HORMONE RECEPTOR POSITIVE (HR+), HUMAN EPIDERMAL GROWTH FACTOR 2 NEGATIVE (HER2-) BREAST CANCER IN CLINICAL PRACTICE: RETROSPECTIVE ANALYSIS FROM LEEDS CANCER CENTRE

Breast cancer (BC) treatment is changing with the advent of novel agents. There is currently little information on real-world UK treatment patterns of patients with HR+, HER2- BC patients. We present characteristics and treatment patterns for such patients treated at a major UK cancer centre. A retrospective review of patient health records from January 2012 to March 2018 (largely prior to NHS reimbursement of CDK 4/6 inhibitors). Eligible patients (female ≥ 18 with metastatic or locally advanced, HR+, HER2- BC) were identified from coded data, unstructured text and clinical review by senior oncologists. Exclusion criteria: clinical trial enrollment, operable local recurrence as only disease site, incomplete treatment record, significant secondary malignancy. Patient characteristics, systemic therapies (by treatment intent), surgery, radiotherapy, use of supportive treatments, monitoring and use of health care resources are presented. 253 eligible patients have been identified (mean age 66 ±14 years, 84% of patients post-menopausal). There were 75 (30%) with metastatic disease at first presentation, 131 (52%) with metastatic disease on recurrence and 47 (19%) with locally advanced disease (T4 and/or N3). Overall, 98% received systemic anti-cancer treatment(s); including chemotherapy (47%), endocrine (92%) and targeted therapy (21%). Amongst the 75 patients with metastatic breast cancer at presentation, the most common therapy regimens were letrozole (56%), anastrozole (29%), exemestane (28%), tamoxifen (28%) and capecitabine (17%); 64% received at least two therapy lines with letrozole-exemestane the most common 2-line sequence (13%). Treatment pathways, sequencing of individual treatments and duration of treatment have been defined for all groups. Real world analysis demonstrates diverse treatment pathways for HR+, HER2- BC, reflecting the personalised care these patients receive. Ongoing longitudinal analyses will demonstrate the impact of new agents on clinical practice. Patients with overt metastatic disease at presentation comprise a substantial proportion of those treated for advanced/metastatic BC.

Detection of endogenously circulating mesenchymal stem cells in human cancer patients.

Mesenchymal stem cells (MSCs) can play a vital role in tumor progression and anticancer therapy response, as demonstrated by various in vitro and in vivo model systems. Their ability to home to developing tumors and modulate the tumor microenvironment, by suppressing T-cell responses and contributing to the tumor stroma, is suggested to have a significant impact on disease progression, metastasis formation, and therapy response. Most evidence, however, is derived from artificial models using exogenously administered MSCs. The contribution of endogenous MSCs to tumor progression is currently unclear. Furthermore, few studies have been conducted in humans. A prospective biomarker study was therefore undertaken in 40 human cancer patients and 10 healthy controls of similar age, aimed at (i) exploring and quantifying circulating MSC levels in healthy volunteers and patients with advanced malignancies, (ii) determining the variability of MSC levels between healthy volunteers and cancer patients with different histologic tumor types, and (iii) exploring biomarkers associated with MSC levels. Significantly increased levels of circulating MSC-like cells were observed in cancer patients when compared to healthy individuals (1.72 fold difference, 95% CI 1.03-2.81%, p = 0.03). In addition, prior systemic therapy was associated with a significant increase in MSC-like cells (1.73 fold difference, 95% CI 1.02-2.95, p = 0.04). These results indicate that the amount of endogenously circulating MSCs in humans is increased in response to cancer, and that systemic anticancer treatment can influence MSC levels. Further research is needed to determine whether MSCs have a predictive value.

How to feed patients with gastrointestinal mucositis.

Gastrointestinal mucositis is a frequent side effect of systemic anticancer treatment and radiotherapy. The occurrence endangers body resources by decreasing food intake and absorption. This review highlights new developments in treatment and prevention. Recent clinical practice guidelines recommend supplying adequate amounts of energy and nutrients to cancer patients undergoing anticancer treatments. This requires repeated screening for risk of malnutrition and in at-risk patients, assessment of food intake and nutritional status, followed by nutritional interventions targeted at individual deficiencies and tolerance to oral, enteral or parenteral feeding. Recent preclinical data report beneficial effects of stimulating the sensor for cell damage signals TRPA1, blocking histamine H2 receptors or supplying probiotics. In a recent clinical trial, amifostine reduced gastrointestinal symptoms and was well tolerated. Probiotics are studied in ongoing clinical trials and glucagon-like peptide 2 analogues are considered for future trials. Due to limited options available today, it has been suggested to also consider several plant-based complementary therapies. Although options for prevention and treatment of chemotherapy or radiotherapy-induced gastrointestinal mucositis today are still limited, inadequate energy and nutrient intake should trigger nutritional interventions, including counselling, oral nutritional supplements, tube feeding and parenteral nutrition. To prevent gastrointestinal mucositis, several new agents have shown promising results in preclinical trials.

Thirty-day mortality after systemic anticancer treatment as a real-world, quality-of-care indicator: the Northland experience.

Systemic anticancer treatment (SACT) at the end of life is considered poor practice due to its futility and associated toxicities. Consequently, 30-day mortality after SACT is increasingly recognised as a potential real-world quality-of-care indicator in medical oncology. Whangarei Base Hospital (WBH) provides outpatient SACT treatment to all patients living in the Northland region of New Zealand. The goal of this study was to report our 30-day mortality after SACT and to contribute to the experience of its use in Australasia. In this retrospective study, the WBH electronic database was searched to identify all patients who had received SACT in WBH from 1 January 2012 to 31 December 2016. Patients who died within 30 days of their last treatment were shortlisted. Records were reviewed identifying key demographic, disease, treatment and mortality data. Composite 30-day mortality index and that of each tumour stream were calculated. Key findings were described using descriptive statistics. Over 5 years, 1103 patients received SACT in WBH, with 57 patients dying within 30 days of treatment, resulting in a composite 30-day mortality rate of 5.17%. One patient died receiving curative intent SACT. More deaths occurred in SACT-naïve patients and during the first two cycles of therapy. Of the deaths, 28% was attributed to SACT, while 59.7% was attributed to cancer progression. Thirty-day mortality rates were comparable to studies from larger institutions. We demonstrated the feasibility of this index for auditing practice in smaller oncology units over a longer timeframe.

P1.03-043 30-Day Mortality Following Systemic Anti-Cancer Treatment for NSCLC at a Single Canadian Cancer Centre

P1.03-043 30-Day Mortality Following Systemic Anti-Cancer Treatment for NSCLC at a Single Canadian Cancer Centre

Long-term efficacy and safety of duloxetine in the management of painful chemotherapy induced peripheral neuropathy.

236 Background: Accordingly, Quality of life in the survivorship of patients with cancer is becoming one of the important issues with a development of systemic anticancer treatment. About 40% of the patients who receive chemotherapeutic agents which have neuropathic potential suffer from painful CIPN. Various approaches to relieve the pain associated with CIPN have been attempted in clinical practice. Previously duloxetine, a dual reuptake inhibitor of serotonin and norepinephrine, has been reported to reduce painful CIPN when administered for 5 weeks. We retrospectively investigated the effect of duloxetine on the pain associated with CIPN over a prolonged period of administration. Methods: Between December 2014 and December 2016, patients with advanced cancer who complained of CIPN during or after systemic chemotherapy were eligible. Initially, 30 mg of duloxetine was administered daily for the first week and 60 mg daily was administered from the second week thereafter. The severity of pain was evaluated using a numerical rating scale from 0 to 10. Study follow-up was performed at regular visits according to the chemotherapy schedule or at the time of evaluation of disease status in the patients who completed systemic chemotherapy. However, the patients were allowed to visit whenever needed. Results: Twenty-seven patients were evaluable, the median age was 64 years (range, 23-83 years), and 11 patients were male and 16 patients were female. Twenty-four of the 27 patients received neurotoxic chemotherapeutic agents such as cisplatin, oxaliplatin, taxane and vinca alkaloid. Patients receiving duloxetine showed a significant reduction in the pain intensity from baseline and the mean decrease in the average pain score was 2.85 (95% CI 2.26-3.44, P &lt; 0.001). Twenty-five (92.5%) of the 27 patients showed decreased pain after the use of duloxetine. Mean duration of treatment was 29 weeks (range, 1~130 weeks). Median duration of response was 19 weeks (range, 4~99 weeks). Treatment-related adverse events were nausea (17.2%), vomiting (3.4%) and dizziness (6.8%). Conclusions: Duloxetine demonstrated a durable efficacy and tolerability for painful CIPN in patients with advanced cancer.

The molecular genetics of chemotherapy-induced peripheral neuropathy: A systematic review and meta-analysis.

Chemotherapy-induced peripheral neuropathy (CIPN) can adversely affect completion of systemic anti-cancer treatment and cause long-term morbidity. Increasingly pharmacogenetic studies have been performed to explore susceptibility to this important adverse effect. A systematic review was conducted to identify pharmacogenetic studies, assess their quality and findings and undertake meta-analysis where possible. 93 studies were included. Notable methodological issues included lack of standardisation and detail in phenotype definition and acknowledgement of potential confounding factors. Insufficient data was presented in many studies meaning only a minority could be included in meta-analysis showing mainly non-significant effects. Nonetheless, SNPs in CYP2C8, CYP3A4, ARHGEF10, EPHA and TUBB2A genes (taxanes), FARS2, ACYP2 and TAC1 (oxaliplatin), and CEP75 and CYP3A5 (vincristine) are of potential interest. These require exploration in large cohort studies with robust methodology and well-defined phenotypes. Seeking standardisation of phenotype, collaboration and subsequently, individual-patient-data meta-analysis may facilitate identifying contributory SNPs which could be combined in a polygenic risk score to predict those most at risk of CIPN.

1455P - Initiation of systemic anti-cancer treatment in the inpatient setting in a tertiary hospital in London

1455P - Initiation of systemic anti-cancer treatment in the inpatient setting in a tertiary hospital in London

The oral education clinic: A pharmacist- and nurse-led clinic to support patients starting oral systemic anti-cancer treatments.

With the increased number of oral systemic anti-cancer treatments available, patients need to be managed safely and effectively in line with national guidance. In response to guidance in 2011, Oxford University Hospitals NHS Foundation Trust implemented an 'Oral Education Clinic'. This nurse- and pharmacist-led clinic facilitates the delivery of patient education, highlighting key safety aspects of drug administration and management, and ensures follow-up is arranged as per protocol. Patients have found this service to be effective and it has had a positive impact on the running of outpatient units, the volume of triage calls, emergency admissions and workload associated with consenting patients to an oral systemic anti-cancer treatments.

30-day mortality after systemic anticancer treatment : Population-based observational study on breast and lung cancer

30-day mortality after systemic anticancer treatment : Population-based observational study on breast and lung cancer

Safety results of the Canadian Expanded Access Program (EAP) of palbociclib (PAL) plus letrozole (L) in postmenopausal patients (pts) with hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer (ABC) deemed appropriate candidates for first-line (1L) endocrine therapy (ET) with L.

e12534 Background: In the PALOMA-2 study, 1L PAL+L prolonged progression-free survival in women with estrogen receptor-positive/HER2- ABC vs placebo + L (hazard ratio 0.58; P&lt; 0.001). Here we assess a cohort of Canadian pts treated with 1L PAL+L for ABC in an EAP study (NCT02142868). Methods: This was an open-label, single-arm study of US and Canadian postmenopausal women (N = 337) with HR+/HER2- ABC for whom 1L ET with L was deemed appropriate. The primary objective was to allow pt access to PAL in combination with L. PAL (125 mg/d orally [3 wk on, 1 wk off]) was administered with L (2.5 mg orally QD) until PAL was commercially available. Secondary objectives included safety and patient-reported outcomes (PROs). Results: 96/97 (99%) treated/enrolled Canadian pts were assessed for safety and PROs (treated pt characteristics: median age 62.5 y, white/Asian [89%/7%], metastatic sites bone/lung/liver [71%/25%/17%], ECOG PS 0-1/2 [93%/7%], 89% with prior systemic anticancer treatment [tx]). Median exposure was 4 x 28 d cycles of tx, and the median average PAL dose was 125 mg/d. All-causality treatment-emergent adverse events (AEs) were reported in 100% pts; 68% had grade 3/4 events, the most common events were neutropenia (61%), infections (3%), and alanine aminotransferase increase (3%). Grade 4 neutropenia and grade 3 febrile neutropenia were reported in 2% and 1% of pts, respectively. Due to AEs, PAL was temporarily discontinued in 59% and 31% had ≥1 dose reduction. The main reasons pts permanently discontinued from the study were sponsor study termination, 77%; objective progression, 11%; and AE related/unrelated to study drug, 6%/2%. All EQ-5D questions were completed by 96% pts at baseline and 85% by end of tx (EOT). At EOT, the median EQ-5D index and the EQ visual analog scale scores were not significantly changed from baseline. Conclusions: A safe and tolerable profile was observed for PAL+L in 1L treatment of Canadian pts with HR+/HER2− ABC, consistent with other studies. Sponsor Pfizer Clinical trial information: NCT02142868.

Phase I/III trial of atezolizumab with carboplatin and etoposide in ES-SCLC in first-line setting (IMpower133).

TPS8584 Background: The first-line standard of care for the majority of patients (pts) with extensive-stage small-cell lung cancer (ES-SCLC) is platinum-based chemotherapy with etoposide, but survival outcomes remain poor (median OS, &lt; 1 year) despite initial response rates ranging from 50-70%. Atezolizumab (atezo), an anti–PD-L1 mAb, prevents the binding of PD-L1 with its receptors PD-1 and B7.1 and restores anticancer T-cell activity. Tolerable safety with promising durability of response has been shown with atezo in pts with ES-SCLC: confirmed ORR was 6% (n = 1/17 [partial response]; DOR of 7 mo) by RECIST v1.1 and 24% by immune-related response criteria (irRC; n = 4/17, with 2 pts on atezo for ≥ 12 mo). Preliminary data also indicate the potential synergy between atezo and platinum-based chemotherapy in NSCLC, whereby durable responses may translate into improved survival over atezo alone. IMpower133 (NCT02763579), a global, Phase I/III, randomized, multicenter, double-blinded, placebo-controlled trial will evaluate the efficacy and safety of 1L atezo + carboplatin + etoposide compared with placebo + carboplatin + etoposide in treatment-naive pts with ES-SCLC. Methods: Pts with measurable (RECIST v1.1) ES-SCLC, who have ECOG PS 0-1 and no prior systemic anticancer treatment, are eligible for the study. Exclusion criteria include untreated CNS metastases and history of autoimmune disease. The study requires submission of tumor tissue, but pts will be enrolled regardless of biomarker status. Pts will be stratified by sex, ECOG PS and presence of treated brain metastases. Eligible pts will be randomized 1:1 to receive four 21-day cycles of atezo (1200 mg IV) or placebo in combination with carboplatin (AUC 5 mg/mL/min IV, d 1) and etoposide (100 mg/m2 IV, d 1-3), followed by maintenance therapy with atezo or placebo until PD per RECIST v1.1. Pts can continue with treatment until persistent radiographic PD, symptomatic deterioration or unacceptable toxicity. Co-primary endpoints are investigator-assessed PFS per RECIST v1.1 and OS. Secondary efficacy endpoints include investigator-assessed ORR and DOR. Safety and tolerability will also be assessed. Approximately 400 pts will be enrolled. Clinical trial information: NCT02763579.

The Addition of Whole-body MRI to Body CT Scans Alters Systemic Anti-cancer Treatment Decisions in Metastatic Breast Cancer

The Addition of Whole-body MRI to Body CT Scans Alters Systemic Anti-cancer Treatment Decisions in Metastatic Breast Cancer

Prevalence of systemic anticancer therapy for patients within the last 30 days of life: experience in a private hospital oncology group.

In recent years, there has been a significant increase in the number of cancer treatments that have become available. However, it has remained difficult to choose the most appropriate time to cease active therapy in individual patients. To determine the proportion of patients being treated with palliative intent who received systemic anticancer treatment in the last 30 days of life. This is a retrospective cohort study conducted within the Melbourne Oncology Group at Cabrini Hospital. Patients managed with palliative intent who died between 1 January 2014 and 30 June 2014 were included. Outcomes measured were the percentage of patients who received systemic anticancer treatment in the last 30 days of life, palliative care referral status, Emergency Department presentations, hospital admissions and place of death. A total of 80 patients was included in the study. Of these patients, 21 (26%) received systemic anticancer treatment in the last 30 days of life. There was no statistically significant difference between patients who received treatment in the last month of life and those who did not in terms of the number of patients who were referred to palliative care, presented to an Emergency Department, were admitted to hospital or died in an acute ward. Although over a quarter of patients dying from advanced cancer received anticancer treatment in the last month of life, these patients did not present acutely to hospital more often and had the same extent of palliative care team involvement.

Afatinib versus gefitinib in patients with EGFR mutation-positive advanced non-small-cell lung cancer: overall survival data from the phase IIb LUX-Lung 7 trial

BackgroundIn LUX-Lung 7, the irreversible ErbB family blocker, afatinib, significantly improved progression-free survival (PFS), time-to-treatment failure (TTF) and objective response rate (ORR) versus gefitinib in patients with epidermal growth factor receptor (EGFR) mutation-positive non-small-cell lung cancer (NSCLC). Here, we present primary analysis of mature overall survival (OS) data.Patients and methodsLUX-Lung 7 assessed afatinib 40 mg/day versus gefitinib 250 mg/day in treatment-naïve patients with stage IIIb/IV NSCLC and a common EGFR mutation (exon 19 deletion/L858R). Primary OS analysis was planned after ∼213 OS events and ≥32-month follow-up. OS was analysed by a Cox proportional hazards model, stratified by EGFR mutation type and baseline brain metastases.ResultsTwo-hundred and twenty-six OS events had occurred at the data cut-off (8 April 2016). After a median follow-up of 42.6 months, median OS (afatinib versus gefitinib) was 27.9 versus 24.5 months [hazard ratio (HR) = 0.86, 95% confidence interval (CI) 0.66‒1.12, P = 0.2580]. Prespecified subgroup analyses showed similar OS trends (afatinib versus gefitinib) in patients with exon 19 deletion (30.7 versus 26.4 months; HR, 0.83, 95% CI 0.58‒1.17, P = 0.2841) and L858R (25.0 versus 21.2 months; HR 0.91, 95% CI 0.62‒1.36, P = 0.6585) mutations. Most patients (afatinib, 72.6%; gefitinib, 76.8%) had at least one subsequent systemic anti-cancer treatment following discontinuation of afatinib/gefitinib; 20 (13.7%) and 23 (15.2%) patients received a third-generation EGFR tyrosine kinase inhibitor. Updated PFS (independent review), TTF and ORR data were significantly improved with afatinib.ConclusionIn LUX-Lung 7, there was no significant difference in OS with afatinib versus gefitinib. Updated PFS (independent review), TTF and ORR data were significantly improved with afatinib. Clinicaltrials.gov identifierNCT01466660.

PA02.03 Access to Care: Malaysia

The Systemic Anti-Cancer Therapy (SACT) dataset collated by Public Health England reported the assessment of factors affecting 30-days mortality in national patient population. Although, the report was impressive, only 3% of lung cancer patient treated with curative intent died within 30 days of starting chemotherapy and 10% for palliative treatment. There was a vast disparity among some hospitals. This concluded that clinical decision making in can certainly impact on cancer mortality(Wallington et al., 2016). In the similar context, clinical decision making in Malaysia and the South East Asia (SEA) are hugely influenced by the affordability factor which can directly influence mortality rates. The clear evidence is seen in Globocan 2012 data. SEA despite having the lowest prevalence for all cancers combined has a highest mortality to incidences ratio when compare with countries which have universal health coverage with better access to innovative care. To understand why the clinical decision making in Malaysia or the SEA region is hugely influenced by the affordability factor we must first dive in the health-care systems in southeast Asia (SEA). There is an enormous social, economic and political diversity within and across the countries in SEA which is formed by its history, geography and position as a major trade route. All these have had contributed not only to the diverse population but also to the wide-ranging nature of its health systems which are at varying stages. This highly diverse health-care system, range from dominant tax-based financing to social insurance and high out-of-pocket payments across the regions. For example, The World Health Report 2006 estimated that the total private finance sources account for 41.8% of total health expenditure in Malaysia which is likely affect the equity of financing because private health payments might impose disproportionate financial burden on households (“WHO | The World Health Report 2006 - working together for health,” 2013). A subsequent analysis showed private health expenditure has dominant role in financing healthcare in five of the seven countries in the SEA, contributing more than 70% of the total spending on health in Laos and Cambodia. This urge for health-financing reform and there are multiple model which are considered by varies government. Among them are financial protections through payroll-financed social health insurance or tax-funded arrangements for formal employment. However, this approach still challenges the informal and the rest of the population with countries such as the Philippines and Vietnam (Tangcharoensathien et al., 2011) A reformed health-financing with universal coverage will not only decrease the Lung cancer mortality as seen in the developed countries but also hugely impact daily clinical practice and increase quality of services provided to the patients. Globocan (2012). Fact Sheets by Cancer. Retrieved October 14, 2016, from http://globocan.iarc.fr/Pages/fact_sheets_cancer.aspx Tangcharoensathien, V., Patcharanarumol, W., Ir, P., Aljunid, S. M., Mukti, A. G., Akkhavong, K., … Wagstaff, A. (2011). Healthfinancing reforms in southeast Asia: challenges in achieving universal coverage. The Lancet, 377(9768), 863873. http://doi.org/10.1016/S01406736(10)618909 Wallington, M., Saxon, E. B., Bomb, M., Smittenaar, R., Wickenden, M., McPhail, S., … Dodwell, D. (2016). 30-day mortality after systemic anticancer treatment for breast and lung cancer in England: a population-based, observational study. The Lancet Oncology, 17(9), 1203–1216. http://doi.org/10.1016/S1470-2045(16)30383-7 WHO | The World Health Report 2006 - working together for health. (2013). WHO. Access, advocacy, patient, Malaysia

OA23.05 First-Line Afatinib versus Gefitinib in EGFRm+ Advanced NSCLC: Updated Overall Survival Analysis of LUX-Lung 7

The irreversible ErbB family blocker afatinib and the reversible EGFR TKI gefitinib are approved for first-line treatment of advanced EGFRm+ NSCLC. This Phase IIb trial prospectively compared afatinib versus gefitinib in this setting. LUX-Lung 7 assessed afatinib (40 mg/day) versus gefitinib (250 mg/day) in treatment-naïve patients with stage IIIb/IV NSCLC harboring a common EGFR mutation (Del19/L858R). Co-primary endpoints were PFS (independent review), time to treatment failure (TTF) and OS. Other endpoints included ORR and AEs. In case of grade ≥3/selected grade 2 drug-related AEs the afatinib dose could be reduced to 30 mg or 20 mg (minimum). The primary analysis of PFS/TTF was undertaken after ∼250 PFS events. The primary OS analysis was planned after ∼213 OS events and a follow-up period of ≥32 months. 319 patients were randomized (afatinib: 160; gefitinib: 159). At the time of primary analysis, PFS (HR [95% CI] 0.73 [0.57‒0.95], p=0.017), TTF (0.73 [0.58‒0.92], p=0.007) and ORR (70 vs 56%, p=0.008) were significantly improved with afatinib versus gefitinib. The most common grade ≥3 AEs were diarrhea (13%) and rash/acne (9%) with afatinib and elevated ALT/AST (9%) with gefitinib. 42% of patients treated with afatinib had ≥1 dose reduction due to AEs; dose reductions were more common in females than males (77%/23%) and non-Asians than Asians (64%/36%). Dose reduction of afatinib did not negatively impact PFS (<40mg vs ≥40mg; HR [95% CI]: 1.34 [0.90‒2.00]) but reduced incidence and severity of drug-related grade ≥3 AEs. Treatment discontinuation due to drug-related AEs was the same in each arm (6%). The data cut-off for primary OS analysis occurred on 8 April 2016. At this time, median treatment duration (range) was 13.7 (0‒46.4) versus 11.5 (0.5‒48.7) months with afatinib and gefitinib. 25% (afatinib) and 13% (gefitinib) of patients received treatment for >24 months. 73% and 77% of patients in the afatinib and gefitinib arms had ≥1 subsequent systemic anti-cancer treatment, with 46% and 56% receiving a subsequent EGFR-TKI including osimertinib (14%)/olmutinib (14%). OS data, including subgroup analysis with respect to subsequent therapy will be presented at the meeting. Afatinib significantly improved PFS, TTF and ORR versus gefitinib in EGFRm+ NSCLC patients, with a manageable AE profile and few drug-related discontinuations. Dose adjustment of afatinib reduced drug-related AEs without compromising efficacy. Primary OS analysis will be reported.

Hepatitis B virus reactivation in patients with solid tumors receiving systemic anticancer treatment

Hepatitis B virus (HBV) reactivation is a well-known risk during chemotherapy for hematological malignancies with reported rates ranging between 14% and 72%. However, there is a paucity of data regarding HBV infection management and reactivation risk in patients receiving systemic treatments for solid tumors. We conducted a PubMed search for publications from January 1990 until May 2016 related to HBV reactivation. The search terms were 'hepatitis B reactivation', cross-referenced with 'chemotherapy', then 'hepatitis B' cross-referenced with International Non-proprietary Name of each of the most used chemotherapy drugs in solid tumors. From these data, a grading of HBV reactivation risk and recommendations for management are given for most frequently used anticancer drugs in solid tumors. Most drugs used for the treatment of solid tumors can induce hepatitis B reactivation in HBs antigen-positive patients. HBV screening can be recommended before systemic treatment initiation. Pre-emptive antiviral treatment can reduce the risk of HBV reactivation and prevent chemotherapy disruption.

30-day mortality after systemic anticancer treatment for breast and lung cancer in England: a population-based, observational study

SummaryBackground30-day mortality might be a useful indicator of avoidable harm to patients from systemic anticancer treatments, but data for this indicator are limited. The Systemic Anti-Cancer Therapy (SACT) dataset collated by Public Health England allows the assessment of factors affecting 30-day mortality in a national patient population. The aim of this first study based on the SACT dataset was to establish national 30-day mortality benchmarks for breast and lung cancer patients receiving SACT in England, and to start to identify where patient care could be improved.MethodsIn this population-based study, we included all women with breast cancer and all men and women with lung cancer residing in England, who were 24 years or older and who started a cycle of SACT in 2014 irrespective of the number of previous treatment cycles or programmes, and irrespective of their position within the disease trajectory. We calculated 30-day mortality after the most recent cycle of SACT for those patients. We did logistic regression analyses, adjusting for relevant factors, to examine whether patient, tumour, or treatment-related factors were associated with the risk of 30-day mortality. For each cancer type and intent, we calculated 30-day mortality rates and patient volume at the hospital trust level, and contrasted these in a funnel plot.FindingsBetween Jan 1, and Dec, 31, 2014, we included 23 228 patients with breast cancer and 9634 patients with non-small cell lung cancer (NSCLC) in our regression and trust-level analyses. 30-day mortality increased with age for both patients with breast cancer and patients with NSCLC treated with curative intent, and decreased with age for patients receiving palliative SACT (breast curative: odds ratio [OR] 1·085, 99% CI 1·040–1·132; p<0·0001; NSCLC curative: 1·045, 1·013–1·079; p=0·00033; breast palliative: 0·987, 0·977–0·996; p=0·00034; NSCLC palliative: 0·987, 0·976–0·998; p=0·0015). 30-day mortality was also significantly higher for patients receiving their first reported curative or palliative SACT versus those who received SACT previously (breast palliative: OR 2·326 99% CI 1·634–3·312; p<0·0001; NSCLC curative: 3·371, 1·554–7·316; p<0·0001; NSCLC palliative: 2·667, 2·109–3·373; p<0·0001), and for patients with worse general wellbeing (performance status 2–4) versus those who were generally well (breast curative: 6·057, 1·333–27·513; p=0·0021; breast palliative: 6·241, 4·180–9·319; p<0·0001; NSCLC palliative: 3·384, 2·276–5·032; p<0·0001). We identified trusts with mortality rates in excess of the 95% control limits; this included seven for curative breast cancer, four for palliative breast cancer, five for curative NSCLC, and seven for palliative NSCLC.InterpretationOur findings show that several factors affect the risk of early mortality of breast and lung cancer patients in England and that some groups are at a substantially increased risk of 30-day mortality. The identification of hospitals with significantly higher 30-day mortality rates should promote review of clinical decision making in these hospitals. Furthermore, our results highlight the importance of collecting routine data beyond clinical trials to better understand the factors placing patients at higher risk of 30-day mortality, and ultimately improve clinical decision making. Our insights into the factors affecting risk of 30-day mortality will help treating clinicians and their patients predict the balance of harms and benefits associated with SACT.FundingPublic Health England.