Use of oncology electronic learning resources to learn about geriatric oncology.

11033 Background: Despite the aging population driving cancer growth, oncology trainees receive little training in geriatrics. While electronic resources, such as ASCO University, may help meet this gap, use of available geriatric oncology (GO) modules is low. We sought to understand why by exploring how oncology trainees currently learn about GO, their preferred methods for learning about GO, and their attitudes towards e-learning and geriatrics. Methods: Canadian medical oncology residents and recent graduates were electronically surveyed about the following domains: demographics, self-directed learning practices, use of electronic resources, perceived facilitators and barriers to e-learning, and geriatric oncology teaching. Descriptive statistics were used to analyze the data. Results: Respondents (n = 47) were mostly aged < 35 (66%). Respondents felt that learning about older adults was important (mean 4.3±1.0 out of 5) and generally felt comfortable caring for them (mean 3.9±0.9 out of 5) despite minimal training in geriatrics.Almost half (48.9%) received 0-2 hours of teaching in GO during residency, with the majority (59.6%) receiving teaching in clinic, 36.2% through lectures and 21.3% via seminars. Respondents also learned about GO through reading journal articles (42.6%), modelling in clinic (36.2%), reading a textbook (19.2%) or attending a conference (19.2%). Respondents preferred to learn about GO through on-site lectures (46.8%), dinner meetings (42.6%), case discussion (42.6%) and attending conferences (38.3%). Although overall respondents highly valued electronic learning (mean 4.3±0.75 out of 5), only a minority (8.5%) had received GO teaching electronically using e-modules and only 23.4% respondents were aware of e-learning resources in GO. In contrast most respondents (83%) had used an e-learning resource to learn about oncology. The most common oncology e-resources used were ASCO University (61.7%), Oncology Education (61.7%), and ASCO meeting videos (44.7%). Conclusions: Although oncology trainees value and commonly use e-learning resources, e-learning is not a common or preferred way to learn about GO, potentially due to lack of awareness about these resources. Future research will explore whether the current methods of educating oncology learners about older adults are appropriate and sufficient, as well as how trainees value and prioritize learning about topics that are not included in the formal curricula.

Association of objective response by mRECIST with better overall survival (OS) in patients with advanced hepatocellular carcinoma (HCC) treated with systemic therapies: A systematic review and meta-analysis of randomized controlled trials.

586 Background: EASL guidelines for management of HCC recommends assessing tumor response according to mRECIST at all stages of the disease (EASL guidelines, J Hep 2018). Several studies have reported that objective response by mRECIST predicted overall survival (OS) but definitive data are still lacking. Methods: The PubMed database and ASCO meeting library were searched for full reports of randomized trials in patients with advanced HCC treated by systemic therapy up to August 31, 2018. We search strategy used the following terms: HCC, mRECIST, OS and objective response rate (ORR). We assess the association between ORR and OS in a meta-analysis of pooled data by using random effects model comparing patients achieving objective response (complete or partial response) versus non responders (stable disease, progressive disease) and displayed the results as per hazard ratio (HR, 95% CI). Results: Among 14 articles assessing response by mRECIST to systemic therapies in randomized studies in advanced HCC, 4 studies (5 trials) including 1,463 patients were considered eligible. Systemic therapies tested included lenvatinib, sorafenib, brivanib and nintedanib. Overall, ORR as per mRECIST ranged from 11.5% to 18.8%, being the median OS for responders of 18.5 to 27.2 mo (as opposed 8.9 to 11.4 for non-responders). As per random effects model, the HR for overall survival (responders versus non responders) was 0.47 (95% confidence interval 0.34–0.66, p<0.001). Conclusions: Objective response by mRECIST to systemic therapies in patients with advanced HCC is significantly and strongly associated to OS. Patients achieving an objective response can expect a significantly longer OS.

Effect size as a tool to identify subpopulations with improved clinical outcomes in metastatic colorectal cancer.

252 Background: ASCO defined meaningful trial endpoints in colorectal cancer (CRC) to include OS HR ≤0.67 (Ellis, JCO 2014). This measure is limited in identifying treatment benefit for subgroups from heterogeneous populations. Effect size (Glass’s Δ) calculates the absolute difference in median clinical outcomes normalized to the control group standard deviation. We hypothesized that durable effect sizes ≥2 would be useful in predicting which trials possess subgroup populations of clinical significance despite a HR > 0.67. Methods: Prospective phase II-III trials in metastatic CRC from the ASCO Meeting Library (2016-2019) were cataloged by clinical outcomes of PFS and OS. Effect size was calculated from trials reporting confidence intervals and compared with absolute difference in clinical outcome, hazard ratio and therapeutic intervention. Trials with an indeterminant HR, yet effect size > 2 were reviewed in subgroup analyses. Results: 385 abstracts were reviewed with 99 clinical analyses available for effect size calculation. Absolute difference in PFS correlated with effect size (R = 0.64) and was inversely proportional to HR (R = -0.63). The absolute difference in OS correlated with effect size (R = 0.69) and was inversely proportional to HR (R = -0.57). When stratified by clinically significant HR (defined ≤0.67), median effect size for PFS was 13.7±13.3 (SD) which was significantly different from HR > 0.67 with median effect size 1.0±3.8 (p < 0.001). Median effect size for OS when stratified by HR ≤0.67 was 3.7±2.5 which was significantly different when compared to endpoints with HR > 0.67 with median effect size 0.9±1.4 (p < 0.003). Subgroup populations with survival benefit included combination checkpoint blockade durvalumab/tremelimumab vs supportive care with effect size 3.1 (HR 0.72; NCT02870920). First-line PFS benefit was predicted in KRAS wildtype liver-limited CRC treated with FOLFOX+cetuximab vs FOLFOX+bevacizumab by effect size of 3.2 (HR 0.80; NCT01836653). Conclusions: Effect size holds potential as a measure to delineate improved clinical outcomes from heterogeneous populations and could identify those trials for which further subgroup analysis should be explored.

Prophylactic Hyperthermic Intraperitoneal Chemotherapy (HIPEC) for Gastric Cancer—A Systematic Review

Survival after potentially curative treatment of gastric cancer remains low, mostly due to peritoneal recurrence. This descriptive review gives an overview of available comparative studies concerning prophylactic hyperthermic intraperitoneal chemotherapy (HIPEC) for patients with gastric cancer with neither clinically evident metastases nor positive peritoneal cytology who undergo potentially curative gastrectomy. After searching the PubMed, Embase, CDSR, CENTRAL and ASCO meeting library, a total of 11 studies were included comparing surgery plus prophylactic HIPEC versus surgery alone (SA): three randomised controlled trials and eight non-randomised comparative studies, involving 1145 patients. Risk of bias was high in most of the studies. Morbidity after prophylactic HIPEC was 17–60% compared to 25–43% after SA. Overall survival was 32–35 months after prophylactic HIPEC and 22–28 months after SA. The 5-year survival rates were 39–87% after prophylactic HIPEC and 17–61% after SA, which was statistically significant in three studies. Peritoneal recurrence occurred in 7–27% in the HIPEC group, compared to 14–45% after SA. This review tends to demonstrate that prophylactic HIPEC for gastric cancer can be performed safely, may prevent peritoneal recurrence and may prolong survival. However, studies were heterogeneous and outdated, which emphasizes the need for well-designed trials conducted according to current standards.

Is There a Standard Adjuvant Therapy for Resected Pancreatic Cancer?

Surgical resection remains the only treatment that offers a potential chance of long-term survival. Unfortunately, about 80% of patients treated with curative intent will develop recurrence. Since 2001, adjuvant therapy with gemcitabine or 5-fluorouracyle was recommended. This approach allows a median overall survival (OS) of around 23 months, and 5-year survival of 22%. In recent years, two phase-3 trials investigating new chemotherapy regimens resulted in considerably improved survival times. The doublet gemcitabine–capecitabine has shown improvement in OS from 25.5 to 28 months (p = 0.032) compared to gemcitabine, in the ESPAC-4 trial. Later, preliminary results of PRODIGE 24 trial presented at the 2018 ASCO meeting showed a superiority of a combination chemotherapy regimen with fluorouracil, leucovorin, irinotecan, and oxaliplatin (mFOLFIRINOX) when compared to gemcitabine alone, both in terms of median disease-free survival (21.6 vs. 12.8 months, p < 0.0001) and OS (54.4 vs. 35 months, p = 0.003). Contrary to chemotherapy, the role of adjuvant radiotherapy is still controversial, even in the case of R1 surgery. A randomized trial exploring the role of chemoradiotherapy in this setting is now ongoing in the US (RTOG-0848). Overall, the management of localized pancreatic adenocarcinoma is evolving. In this review, we summarize the current status and the most up-to-date developments in adjuvant treatment.

ASH 2018

Anfang Dezember fand in San Diego/USA der Jahreskongress der American Society of Hematology (ASH) statt. Traditionell nimmt die Supportivtherapie beim ASH-Kongress eine weniger bedeutende Rolle als etwa beim ASCO-Meeting, das supportiven Themen mittlerweile eigene Sessions widmet. Dennoch gab es beim diesjährigen ASH interessante Neuigkeiten zur Supportivtherapie bei hämatologischen Malignomen, die wir hier schwerpunktmäßig vorstellen. Im Fokus standen die Prophylaxe venöser Thromboembolien, die Vorteile der Eisenchelation bei transfusionspflichtigen Patienten mit MDS sowie das bessere Verständnis der Neurotoxizität beim therapeutischen Einsatz von CAR-T-Zellen.

An analysis of growth patterns of targeted therapies (TTs) using keywords from ASCO annual meeting abstracts.

e18084 Background: The number of TTs approved to treat cancer patients has increased dramatically in the past decades. We analyzed how frequently 27 oncology targets (and associated therapies) appeared in ASCO meeting abstracts since 2005 to explore if future drug development patterns could be predicted. Methods: We obtained abstracts from the ASCO Center for Research & Analytics. We used keyword abstraction to calculate the percentage of abstracts referencing 27 specific target/drug combinations each year, and we categorized them into high (HV), medium (MV), and low volume (LV) groups based on percentage in 2018. Results: Table shows data since 2012 for the HV group. The percentages of MV (BCR/ABL, CDK4/6, CD20, MEK, CTLA4, iMID, PARP, PI3K, proteasome inhibitors) and LV (BCL2, BTK, CD19, CD30, CD38, HDAC, IDH1, IDH2, and NTRK) in 2018 were less than 1.7%. The HV group was associated with more FDA-approved therapies (41) than the MV (23) and LV (13) groups. The HV and MV groups are likely enriched for more mature targets, as the median date of relevant drug approvals is earlier (11/2012 and 4/2013, respectively) than the LV group (4/2016). Growth patterns are consistent with key regulatory milestones. The number of abstracts with PD-1/PD-L1-related keywords has grown more rapidly than any other drug/target combination. This growth begins soon before FDA approvals for a diversity of relevant indications. Continued growth likely reflects ongoing clinical trials of several other PD-1/PD-L1 inhibitors and combinations. We identified similar growth trends for other targets just prior to key regulatory approvals. Conclusions: Our analysis revealed interesting growth patterns for key oncology target/drug combinations. Future work will explore whether we can extend the analysis to help predict the evolution of development programs for new targets. [Table: see text]

Comprehensive report of anti-CD19 chimeric antigen receptor T cells (CAR-T) associated non-relapse mortality (CART-NRM) from FAERS.

2540 Background: CAR-T cells targeting CD19 positive B-cells have improved outcomes for relapsed/refractory non-Hodgkin lymphoma (NHL) and B-cell acute lymphoblastic leukemia (B-ALL). CAR-T emergent toxicities for FDA approved therapies leading to non-progression related death have been reported in the pivotal studies. However, they are underreported and there remains a need to obtain a comprehensive report of NRM emergent with anti-CD19 CAR-T. Methods: We retrospectively searched FDA adverse events reporting system (FAERS) for all adverse events (AE) related to “Tisagenlecleucel(T)” and “Axicabtagene ciloleucel(AC)” reported from 2013-2018. FAERS contains AEs from clinical trials and standard of care patients. All cases with the outcome of death were analyzed. Results: Total numbers of anti-CD19 CAR-T pts reported were 636, out of which 288 cases received “T” and 348 received “AC”. Out of total 129 total deaths, 95 died due to non-disease progression. Patient characteristics are summarized in Table. CART-NRM for entire cohort was 15%; 21% for “T” and 10% for “AC”. Major toxicities reported include CRS, hematological, cardiovascular, neurological and infectious. Difference in mortality is likely related to different patient population, diagnoses and the CAR-T construct. Conclusions: CART-NRM remains considerably high at 15%. Our analysis highlights the major toxicities and informs the potential opportunities for interventions to reduce mortality. We will present updated data with comparative analysis of published clinical studies at the upcoming ASCO Meeting in Chicago. [Table: see text]

Analysis of the Use and Impact of Twitter During American Society of Clinical Oncology Annual Meetings From 2011 to 2016: Focus on Advanced Metrics and User Trends

Purpose: The use of social media, in particular Twitter, has substantially increased among health care stakeholders in the field of hematology and oncology, with an especially sharp increase in the use of Twitter during times of major national meetings. The most attended meeting in the oncology field is the ASCO annual meeting. Little is known about the detailed metrics involved in the use, volume, and impact of Twitter during the ASCO annual meeting. Methods: We conducted a retrospective review of tweets during the ASCO annual meetings from 2011 to 2016. The total data set encompassed 190,732 tweets from 39,745 authors over six consecutive ASCO meetings from 2011 to 2016 (inclusive). Tweets, all publically available, were collected by Nephrology On-Demand Analytics. Results: The number of individual authors increased from 1,429 during the 2011 ASCO meeting to 15,796 during the 2016 ASCO meeting, an 11-fold increase over the total 5-year period. There was a notable increase in tweets from the 2011 ASCO meeting (n = 7,746) to the 2016 ASCO meeting (n = 72,698), a nine-fold increase during the study period. The most commonly tweeted term or topic changed over time, generally reflecting the breakthroughs of each designated year; these terms were “melanoma” for both the 2011 and 2012 ASCO meetings; “breast cancer” for the 2013 ASCO meeting; “lung cancer” for the 2014 ASCO meeting; and “ImmunOnc” or “immunotherapy/immuno-oncology” for both the 2015 and 2016 ASCO meetings. Conclusion: The use of Twitter among health care stakeholders during the ASCO meeting has markedly increased over time, demonstrating the increasing role of social media in the dissemination of findings at the most highly attended hematology and oncology conference of the year.