First-line Treatment For Metastatic Disease Research Articles

Calibrating Observational Health Record Data Against a Randomized Trial

The conditions required for health record data sources to accurately assess treatment effectiveness remain unclear. Emulation of randomized clinical trials (RCTs) with health record data and subsequent calibration of the results can help elucidate this. To pilot an emulation of the KEYNOTE-189 RCT using a commercially available electronic health record (EHR) data source. This retrospective cohort study used an EHR database spanning from April 2007 to February 2023. Follow-up began on treatment initiation and proceeded until an outcome event, loss to follow-up, end of data, or end of study period (640 days). The population-based cohort was ascertained from EHRs provided by 52 health systems across the US. Eligibility criteria were defined as closely as possible to the benchmark RCT. Patients with non-small cell lung cancer initiating first-line treatment for metastatic disease were included. Patients with evidence of squamous non-small cell lung cancer, primary nonlung malignant neoplasms, or identified EGFR/ALK variations were excluded. Data were analyzed from June to October 2023. Initiation of first-line pembrolizumab and chemotherapy and chemotherapy alone. Chemotherapy in both groups was defined as a combination of pemetrexed and platinum-based (carboplatin or cisplatin) therapy. Outcomes of interest were 12-month survival probability and mortality hazard ratio (HR). A total of 1854 patients (mean [SD] age, 63.7 [9.6] years; 971 [52.4%] men) were eligible, including 589 patients who initiated pembrolizumab and chemotherapy and 1265 patients who initiated chemotherapy only. The cohort included 364 Black patients (19.6%) and 1445 White patients (77.9%). The 12-month survival probabilities were 0.60 (95% CI, 0.54-0.65) in the pembrolizumab group and 0.58 (95% CI, 0.55-0.62) in the chemotherapy-only group, compared with 0.69 (95% CI, 0.64-0.74) in the KEYNOTE-189 pembrolizumab group and 0.49 (95% CI, 0.42-0.56) in the KEYNOTE-189 chemotherapy-only group. The mortality HR was 0.95 (95% CI, 0.78-1.16), compared with 0.49 (95% CI, 0.38-0.64) in the KEYNOTE-189 RCT. In this cohort study piloting an RCT emulation, results were incongruous with the benchmark trial. Differences in patient treatment and data capture between the RCT and EHR populations, confounding by indication, treatment crossover, and accuracy of captured diagnoses may explain these findings. Future feasibility assessments will require data sources to have important oncology-specific measures curated.

Abstract PO4-10-04: Treatment differences by race and age in metastatic hormone receptor-positive/HER2-negative breast cancer

Abstract Introduction: Black and younger patients are more likely to have aggressive forms of breast cancer. Endocrine therapy (ET) plus a CDK4/6 inhibitor is the standard of care first-line therapy for patients with hormone receptor-positive, HER2-negative (HR+/HER2-) metastatic breast cancer (MBC). Recent data has shown better outcomes with this approach compared to chemotherapy, even for patients with aggressive disease. Our study looked at differences in first-line treatment among Black and younger women with HR+/HER2- MBC. Methods: Clinical characteristics, treatment, and outcomes of patients diagnosed with HR+/HER2- MBC between 2011-2022 were retrieved from the UNC Metastatic Breast Cancer Database. Log binomial regression modeling compared treatment choices by group, and Cox proportional hazards regression modeling evaluated progression-free survival (PFS) from the start of treatment. Results: 524 patients were included in this analysis. 30% were young patients (< 50 years of age), 20% were Black patients, 62% had only 1 site of metastasis and 51% had visceral involvement. When looking at first-line treatment for metastatic disease, 21% of overall patients had received chemotherapy. The likelihood of receiving chemotherapy was higher for younger verses (vs) older patients (29% vs 18%, RR=1.63, p=0.004), for Black vs White patients (31% vs 18%, RR=1.71, p=0.002), and for those with visceral vs non-visceral involvement (26% vs 16%, RR=1.67, p=0.004). A model including age, race, and visceral involvement showed similar findings. Among patients who received ET as the first line treatment for metastatic disease, the likelihood of receiving CDK 4/6 inhibitors in addition to ET was lower for young Black patients compared to young White patients (41% vs 74%, RR=0.55, p=0.02). However, among older patients >=50, no significant difference was seen by race (Blacks 60% vs Whites 56%, RR=1.1, p=0.61). Adjusting for visceral involvement showed similar findings. Patients who received ET (with or without CDK 4/6 inhibitors) had better PFS compared to patients receiving chemotherapy as first-line therapy (HR 0.65, 95% CI 0.49, 0.88, p=0.005), this held true after adjusting for age, race, treatment group and visceral involvement (HR 0.7, p=0.02). A stratified analysis showed similar findings within Black patients (HR 0.42, p=0.003), and young patients (HR 0.55, p=0.01). Conclusion: Overall, Black and younger patients were more likely to receive chemotherapy as the first-line treatment for metastatic disease. Among patients who received ET as the first-line treatment for MBC, young Black patients were less likely to receive CDK 4/6 inhibitors compared to young White patients. Further studies are needed to outline the multi-level factors contributing to the identified disparities in care among patients with HR+/HER2- MBC. Citation Format: Yara Abdou, Joannie Ivory, Allison Deal, Ally Wardell, Amy Wheless, Claire Dees, Lisa Carey. Treatment differences by race and age in metastatic hormone receptor-positive/HER2-negative breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-10-04.

Practical Guidance on Abemaciclib in Combination with Adjuvant Endocrine Therapy for Treating Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative High-Risk Early Breast Cancer.

The most common subtype of breast cancer is hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer, accounting for 65-70% of all breast cancer cases diagnosed in the United States. Until 2015, single-agent endocrine therapy (ET) was the recommended first-line treatment for metastatic HR-positive, HER2-negative breast cancer. However, the paradigm has since shifted, as targeted therapy is now recommended in combination with ET. The cyclin-dependent kinase (CDK) 4/6 inhibitors have revolutionized the treatment of this breast cancer subtype, and combining either palbociclib, ribociclib, or abemaciclib with ET is now the standard first-line treatment for metastatic disease. Results of clinical trials in the metastatic setting have demonstrated that treatment with the combination of a CDK4/6 inhibitor and ET rather than ET alone is associated with longer overall survival, longer progression-free survival, and better objective response rates. Each of the CDK4/6 inhibitors has been investigated in combination with ET in patients with early-stage HR-positive, HER2-negative breast cancer who are at high risk of relapse. In October 2021, abemaciclib was the first CDK4/6 inhibitor approved in combination with ET by the US Food and Drug Administration for adjuvant treatment of patients with HR-positive, HER2-negative, high-risk early breast cancer. Herein, we provide practical guidance on the use of abemaciclib in combination with ET for HR-positive, HER2-negative, high-risk early breast cancer to assist clinicians in their day-to-day practice, and we review clinically relevant topics of dosing, side effect management, sequencing and optimal timing for initiation, and patient selection.

Real-world data on efficacy and safety of pembrolizumab in the first-line treatment of metastatic lung cancer in patients with PD-L1 expression >0% - a single center experience.

With the advent of immunotherapy, there has been a significant improvement in the outcomes of non-small cell lung cancer treatment. Several clinical trials have confirmed the efficacy and safety of pembrolizumab, but research with real-world data is needed to confirm the findings from clinical trials. In this retrospective study, data on the treatment of lung cancer with pembrolizumab were analyzed in 78 patients who started pembrolizumab therapy as first-line treatment for metastatic disease at University Hospital Centre Osijek, from May 15, 2018, until December 31, 2021. November 30, 2022, was set as the last date of data monitoring. Patients who had received less than 3 cycles of pembrolizumab were excluded from the study. The main objectives of the study were OS (overall survival) and PFS (progression-free survival). The differences in the incidence and type of adverse events between the two groups of patients were also compared. Kaplan-Meier analysis of the survival determined that the median OS was 20 months and PFS was 13 months. Although OS and PFS are longer in patients with PD-L1 (programmed death-ligand 1) ≥ 50%, the differences are not statistically significant. The most commonly reported adverse events related to pembrolizumab treatment were gastrointestinal adverse events. No significant differences were found in the frequency of occurrence of certain adverse events between the two groups of patients. This study demonstrates that real-world data for pembrolizumab treatment of non-small cell lung cancer confirm the efficacy and safety indicated by clinical trials. Nevertheless, it is necessary to assess the patient's general condition more objectively before starting the treatment.

The role of CDK4/6 inhibitors in older and younger patients with breast cancer: A systematic review and meta-analysis.

Cyclin-dependent kinase 4/6 (CDK4/6) inhibitors have an extremely important impact on the treatment of hormone-sensitive breast cancer (BC) and have radically changed the first-line treatment for metastatic disease with increased rates of treatment response, overall survival (OS), and progression-free survival (PFS). We performed a pooled analysis of randomized trials to validate or refute the hypothesis that there is a significant survival benefit of adding anti-CDK4/6 inhibitors to standard endocrine therapy (ET) in older patients with advanced BC. We selected only English-language phase II/III randomized controlled trials that compared ET alone with ET with anti-CDK4/6 inhibitors in the treatment of advanced BC, with subgroups reporting the outcomes of elderly patients (usually at least 65 years). The primary endpoint was OS. The review process led to the inclusion of 12 articles and two meeting abstracts, including a total of 10 trials. The addition of CDK4/6 inhibitors to ET (letrozole or fulvestrant) significantly reduced mortality risk by 20% in younger patients (fixed-effect model; HR 0.80; 95% CI 0.72-0.9; p<0.01) and 21% in older BC patients (HR 0.79; 95% CI 0.69-0.91; p<0.01). No OS data were available for patients ≥70 years. This large, pooled analysis is the first to demonstrate that CDK4/6 inhibitors confer OS and PFS benefits in elderly patients (those aged ≥65 years) with advanced ER+BC and to indicate that it should be discussed with and offered to all patients after geriatric assessment and according to the toxicity profile.

Second-line endocrine therapy (ET) with or without palbociclib (P) maintenance in patients (pts) with hormone receptor-positive (HR[+])/human epidermal growth factor receptor 2-negative (HER2[-]) advanced breast cancer (ABC): PALMIRA trial.

1001 Background: Cyclin-dependent kinases 4 and 6 inhibitors (CDK4/6i) in combination with ET has become a standard first-line treatment for pts with endocrine-sensitive, HR[+]/HER2[-] ABC. The optimal treatment after progression on a CDK4/6i remains unknown. This study aims to determine if P maintenance with an alternative ET improves the antitumor activity of second-line treatment in this patient population. Methods: A total of 198 pts with HR[+]/HER2[-] ABC who had disease progression to first-line P plus ET (aromatase inhibitor or fulvestrant) were included. Pts were eligible if they had clinical benefit to the first-line treatment defined as response or stable disease ≥24 weeks, or who had progressed on a P-based regimen in the adjuvant setting with disease progression after at least 12 months of treatment but no more than 12 months following P treatment completion. Pts were randomly assigned (2:1 ratio) to receive P plus second-line ET (letrozole or fulvestrant, based on prior ET) or second-line ET alone. Stratification factors were prior ET and the presence of visceral involvement. Primary endpoint was investigator-assessed progression-free survival (PFS) determined by RECIST v.1.1. Secondary endpoints included overall response rate (ORR), clinical benefit rate (CBR), overall survival, and safety. The 2-sided log-rank test (α = 0.05) had an 80% power to detect a hazard ratio ≤0.59 in favor of P maintenance. Results: Between April 2019 and October 2022, 136 and 62 pts were randomized to receive P+ET and ET, respectively. Pts characteristics were well balanced. Median age was 59 years (range: 33-85), 61.1% were ECOG 0, 61.1% had visceral disease, and 89.9% received aromatase inhibitor + P as first-line treatment for metastatic disease. At median follow-up of 8.7 months and 155 PFS events, median investigator-assessed PFS was 4.2 months (95% CI 3.5–5.8) in the P+ET vs. 3.6 months (95% CI 2.7–4.2) in the ET arm (hazard ratio 0.8, 95% CI 0.6–1.1, p=0.206). This result was consistent across all stratification subgroups. 6-month PFS rate was 40.9% and 28.6% for P+ET and ET, respectively. Among 138 pts with measurable disease, no significant differences were observed in ORR (6.4% vs. 2.3%) or CBR (33.0% vs. 29.5%) for P+ET and ET, respectively. Grade 3-4 adverse events were higher in pts treated with P+ET (45.2% vs. 8.3%) and no new safety signals were identified. No treatment-related deaths were reported. Conclusions: For HR[+]/HER2[-] ABC pts, maintaining P with a second-line ET beyond progression on prior P-based therapy did not significantly improve PFS compared with second-line ET alone. Planned biomarker analysis may help identify which pts are more likely to benefit from this therapeutic approach. Clinical trial information: NCT03809988 .

European Neuroendocrine Tumor Society (ENETS) 2023 guidance paper for digestive neuroendocrine carcinoma.

This ENETS guidance paper, developed by a multidisciplinary working group, provides up-to-date and practical advice on the diagnosis and management of digestive neuroendocrine carcinoma, based on recent developments and study results. These recommendations aim to pave the road for more standardized care for our patients resulting in improved outcomes. Prognosis is generally poor for digestive NEC, most are advanced at diagnosis and median survival in metastatic disease is 11-12 months. Surgery can be of benefit for localized disease after extensive preoperative imaging. Carboplatin in combination with etoposide is recommended as first-line treatment for metastatic disease. Irinotecan with fluoropyrimidines has the best evidence as second-line treatment. Immunotherapy plays a minor role in biomarker-unselected patients. Molecular profiling if available is encouraged to identify new targets. More prospective clinical trials are highly needed to fulfil the unmet needs in this field, especially on new predictive and prognostic biomarkers and to improve survival of patients with advanced disease.

Real world evidence study on treatment patterns and health resource utilization in patients with HR+/HER2- locally advanced or metastatic breast cancer in Korea

Objective To understand current treatment patterns and health care resource utilization (HRU) of women with locally advanced or metastatic breast cancer (advanced breast cancer; ABC) in Korea overall and within patients who had progressed with prior endocrine therapy (as first-line treatment for metastatic disease) and patients with no prior systemic treatment (for advanced disease). Methods A chart review was conducted in 109 patients (women ≥ 18 years old with HR+/HER2- ABC diagnosed between 2015 and 2017) from 11 hospitals. Anonymized data on patient characteristics, treatment patterns and HRU was abstracted. Results Mean (range) age of all patients was 57.5 (40–81) years. Overall, the most common first-, second- and third-line systemic therapy after diagnosis of ABC were letrozole ± palbociclib (51%), endocrine therapy (ET)±everolimus (42%) or chemotherapy (ChT) (39%), and ChT (68%), respectively. In patients progressed with ET (n = 33) and those with no prior systemic treatment (n = 52), the most common first-line treatments were letrozole (82%) and letrozole + palbociclib (42%), respectively. The percentage of patients with at least one grade 3 or higher adverse event during first-line therapy was 93.1% vs 39.2% in patients on a ChT based regimen (N = 29) vs. ET (N = 74). Overall, oncologist visits, at an annual rate of 9.27 (95% CI: 8.87, 9.69) visits per month, and hospitalizations, with an annual rate of 0.44 (95% CI: 0.36, 0.54), and mean (SD) length of stay of 14.3 (10.32) days, were the key drivers of HRU. Conclusions These findings on real world HRU reflected clinical guidelines and severity of ABC. Results can inform future evaluations of new ABC treatments that estimate the health economic impact of their adoption in Korea.

Real-World Efficacy and Safety of Bevacizumab in the First-Line Treatment of Metastatic Cervical Cancer: A Cohort Study in the Total Population of Croatian Patients.

Background Although today it is almost preventable, cervical cancer still represents a significant cancer burden, especially in some developing parts of the world. Since the introduction of bevacizumab in the first-line treatment of metastatic disease, improvements of the outcomes were noted. However, results from randomized controlled trials are often hard to recreate in the real-world setting. Objective To assess the real-world efficacy and safety of bevacizumab as a first-line treatment of advanced cervical cancer. Methods We conducted a retrospective cohort study on the total population of Croatian patients diagnosed with metastatic cervical cancer from 2016 to 2019 who were treated with bevacizumab in combination with cisplatin and paclitaxel (TCB) in the first line. The comparison group was the consecutive sample of patients treated with chemotherapy alone. The primary endpoint was overall survival (OS). Secondary endpoints were progression-free survival (PFS), objective response rate, incidence of adverse events, and the proportion of treatment discontinuation. Results We enrolled 67 patients treated with TCB and a control group of 62 patients treated with chemotherapy alone. The TCB cohort had significantly longer unadjusted OS with a median of 27.0 (95% CI 18.5; not calculable) months, compared to 15.5 (10.7; 30.1) months in the chemotherapy-alone cohort. Adjusted OS was not significantly different. PFS was significantly longer for the TCB cohort, with a median of 10.6 (95% CI 8.5; 15.4) months, than for the chemotherapy-alone cohort, with a median of 5.4 (95% CI 3.9; 9.1) months, even after adjustment for baseline covariates (HRadjusted = 0.60; 95% CI 0.39; 0.94; p=0.027; false discovery rate <5%). Conclusions In a real-world setting, TCB as a first-line treatment of metastatic cervical cancer was associated with longer PFS, better objective disease control rate, and acceptable toxicity profile in comparison to chemotherapy alone. These results may indicate its utility and potential applicability in other parts of the developing world.

Impact of the development of immune related adverse events in metastatic melanoma treated with PD -1 inhibitors.

Some clinical trials have described improved outcomes in patients who develop immune-related adverse events (irAEs) while receiving immune checkpoint inhibitors for advanced melanoma. It is unknown if this effect would be seen in a real-world population. This is a single-center retrospective analysis of all patients receiving single-agent PD-1 inhibitor for unresectable stage III or stage IV melanoma between 2012 and 2018. The majority of patients had cutaneous melanoma and were elderly (put in median and range). Totally 33.3% were BRAF mutated and 66.7% had PD-1 inhibitor as first-line treatment for metastatic disease. Also, 22% of patients had brain metastases at presentation. Of the 87 patients included in this analysis, 48 (55%) developed at least one irAE. Dermatologic toxicities were the most common irAE. The median time to develop any irAE was 12 weeks. Only one patient died of immune-related toxicity. Overall survival in the population of patients that had an irAE was significantly greater than those that did not have any toxicity (21.1 vs. 7.5 months; P < 0.001). The development of endocrine toxicity had the strongest correlation with survival as did patient with grade 1 (NCI V.5) toxicity. The development of multiple toxicities did not correlate with survival. In patients with multiple toxicities, the type of irAE that presented initially did not impact the outcome. These findings add to the growing body of literature suggesting an association between irAEs and immune-checkpoint inhibitor efficacy while suggesting that this benefit may depend on the type of toxicity and severity.

Association of Diet Quality With Survival Among People With Metastatic Colorectal Cancer in the Cancer and Leukemia B and Southwest Oncology Group 80405 Trial

Diet has been associated with survival in patients with stage I to III colorectal cancer, but data on patients with metastatic colorectal cancer are limited. To examine the association between diet quality and overall survival among individuals with metastatic colorectal cancer. This was a prospective cohort study of patients with metastatic colorectal cancer who were enrolled in the Cancer and Leukemia Group B (Alliance) and Southwest Oncology Group 80405 trial between October 27, 2005, and February 29, 2012, and followed up through January 2018. Participants completed a validated food frequency questionnaire within 4 weeks after initiation of first-line treatment for metastatic colorectal cancer. Diets were categorized according to the Alternative Healthy Eating Index (AHEI), Alternate Mediterranean Diet (AMED) score, Dietary Approaches to Stop Hypertension (DASH) score, and Western and prudent dietary patterns derived using principal component analysis. Participants were categorized into sex-specific quintiles. Multivariable hazard ratios (HRs) and 95% CIs for overall survival. In this cohort study of 1284 individuals with metastatic colorectal cancer, the median age was 59 (interquartile range [IQR]: 51-68) years, median body mass index was 27.2 (IQR, 24.1-31.4), 521 (41%) were female, and 1102 (86%) were White. There were 1100 deaths during a median follow-up of 73 months (IQR, 64-87 months). We observed an inverse association between the AMED score and risk of death (HR quintile 5 vs quintile 1, 0.83; 95% CI, 0.67-1.04; P = .04 for trend), but the point estimates were not statistically significant. None of the other diet scores or patterns were associated with overall survival. In this prospective analysis of patients with metastatic colorectal cancer, diet quality assessed at initiation of first-line treatment for metastatic disease was not associated with overall survival.

P-280 The comparison of mFOLFOX-6, mDCF, mFOLFIRINOX in the first-line treatment of advanced gastric cancer

The prognosis of patients (pts) with advanced gastric cancer is poor. There is no single, global standard regimen for the first-line treatment of metastatic disease. We performed a randomized trial to evaluate the safety and efficacy of first-line mFOLFOX-6, mDCF, mFOLFIRINOX in metastatic gastric cancer pts.

Immunotherapy in Advanced Non-Small Cell Lung Cancer.

Traditionally, lung cancer has been treated as an immune-resistant disease with platinum-based chemotherapy serving as the first-line treatment for metastatic disease. The efficacy of immunotherapy has been established for patients with advanced lung cancer in clinical trials, and it has since become the standard of care for patients without targetable mutations, with or without chemotherapy. Previously, lung cancer patients experienced limited responses to immune-based therapy. As clinical trials continued to explore immunotherapy options with checkpoint inhibitors, results showed that immune therapies can create durable responses with manageable toxicities. Patients with advanced non-small cell lung cancer (NSCLC) can experience improved survival when administered immunotherapy over chemotherapy. The first successful immunotherapy treatments developed exploit programmed death 1/programmed death ligand 1 (PD-1/PD-L1) and cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4), immune checkpoint pathways. Combination therapies of PD-1/PD-L1 inhibitors and chemotherapy or PD-1/PD-L1 and CTLA-4 checkpoint pathway inhibitors have also demonstrated improved outcomes for patients with NSCLC. Combination therapy with PD-1 or PD-L1 therapy and chemotherapy has shown benefit for small cell lung cancer patients as well. As immunotherapy changes the treatment paradigm of lung cancer, researchers continue to investigate different combinations, timing, duration, and biomarkers to better understand and improve the efficacy of immune-based therapy for patients with lung cancer.

Abstract P2-15-07: Real-world multicenter, prospective study of the effects of nab-paclitaxel on clinical outcomes and quality of life of patients with metastatic breast cancer in Greece. The ‘ABReast’ study

Abstract Introduction: Nanoparticle albumin-bound (nab)-paclitaxel (nab-P) is approved for the treatment of patients with metastatic breast cancer (MBC) who have failed first-line treatment for metastatic disease and for whom standard, anthracycline containing therapy is not indicated. Real-world evidence on the effectiveness of nab-P is sparse. From this perspective, this non-interventional study was designed to assess the impact of nab-P on the clinical outcomes and the quality of life of patients with MBC in the routine care of Greece. Materials and methods: This multicenter prospective study enrolled consented females with MBC initiated (≤7 days prior to enrollment) on nab-P according to physicians decision. Clinicopathologic parameters and patient-reported outcomes [Functional Assessment of Cancer Therapy-Breast (FACT-B)] were collected at approximately 9-week intervals during the first 12 months of study participation and approximately every 18 weeks thereafter, until the end of the study observation period (maximum 30 months). Results: Between April 2016 and October 2017, 150 eligible patients (99.3% Caucasian) were enrolled in the study in 16 oncology centers. The patients’ median age was 64.5 years (range: 30.7-84.0) and ECOG performance status was 0 in 66.4% and 1 in 26.2%. 45.3% of patients had ≥1 comorbidity (21.3% cardiovascular diseases). The median time elapsed since MBC diagnosis was 22.4 months, while 36.0% of patients were de novo metastatic. The distribution of hormone receptor (HR)/human epidermal growth factor receptor 2 (HER2) status was 74.6% HR+/HER2-, 11.9% HR-/HER2-, 11.2% HR+/HER2+, and 2.2% HR-/HER2+. Most commonly occurring metastatic sites were the bones (55.3%), lung (50.0%), and liver (40.0%). Prior taxane-based therapy was annotated in 40.0% of patients. Of the patients, 11.3% received nab-P as first, 36.0% as second, 23.3% as third, and 29.3% as fourth or further treatment line. A median of 6 cycles (range: 1-33) was administered; 42.7% of the patients completed &amp;gt;6 and 22.0% &amp;gt;8 cycles. Dose reductions were required for 26.0% of the patients, mainly due to toxicity. The objective response rate was 26.7% and the clinical benefit rate was 44.0%. After a median follow-up of 19.3 months, 92 patients had progressed and 57 had died (14 without progression). The median progression-free survival (PFS) was 6.2 months [95% confidence interval (CI): 5.2-7.3]. The 6- and 12-month PFS rates were 50.6% and 30.5%, respectively. The median overall survival was 21.1 months (95% CI: 17.2-not estimable). Liver [hazard ratio (HR): 1.81; 95% CI: 1.24-2.66] and lung (HR: 1.53; 95% CI: 1.04-2.25) metastases were associated with a higher risk of progression or death. No statistically significant change in the patients’ baseline FACT-B total score (median: 93.0) was observed. The serious and non-serious adverse event (AE) incidence rates were 12.7% and 48.0%, respectively with a total of 37 grade ≥3 AEs (not including disease progression) reported. Conclusion: This study generated real-world evidence on the effectiveness of nab-paclitaxel; no new safety signals emerged. Citation Format: Anna Koumarianou, Paris Makrantonakis, Flora Zagouri, Christos Papadimitriou, Athina Christopoulou, Epaminontas Samantas, Christos Christodoulou, Amanda Psyrri, Dimitris Bafaloukos, Gerasimos Aravantinos, Pavlos Papakotoulas, Sofia Baka, Charalampos Andreadis, Athanasios Alexopoulos, Iliada Bombolaki, Katerina Kampoli, Sofia Liori, Kiki Karvounis, Alexandros Ardavanis. Real-world multicenter, prospective study of the effects of nab-paclitaxel on clinical outcomes and quality of life of patients with metastatic breast cancer in Greece. The ‘ABReast’ study [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P2-15-07.

PCN122 COST-EFFECTIVENESS ANALYSIS OF TRASUTUZUMAB EMTANSINE VERSUS TRASTUZUMAB FOR WOMEN WITH HER2+ ADJUVANT BREAST CANCER IN FRANCE

To evaluate the cost-effectiveness of trastuzumab emtansine in women with HER2+ adjuvant breast cancer and a finding of residual invasive disease in the breast or axillary lymph nodes after preoperative systemic treatment in France. A six health states Markov model (invasive disease-free survival, non-metastatic recurrence, remission from a non-metastatic recurrence, first-line treatment of metastatic disease, subsequent treatment lines of metastatic disease and death) adapted to the French setting was used to estimate costs and benefits of trastuzumab emtansine versus trastuzumab on a lifetime horizon. Transition probabilities were derived from KATHERINE in the non-metastatic health-states, a randomized phase III clinical trial comparing trastuzumab emtansine versus trastuzumab, and survival and risk of progression in metastatic health-states were derived from EMILIA in case of recurrence within 18-months and from CLEOPATRA and M77001 for later recurrence. Health state utilities were estimated from the KATHERINE trial in the non-metastatic health states using EQ-5D-3L adjusted to the French population and from literature for the metastatic health states. Costs (2019) were calculated from a wide payer perspective (collective). Grade 3-4 adverse events (AE) were considered with impact on cost and loss of quality of life. Costs and outcomes were discounted at 4%. Sensitivity and scenario analyses were performed. Compared to trastuzumab, trastuzumab emtansine was associated with a gain of 2.05 (15.21 versus 13.17) quality-adjusted life years (QALYs) and a gain of 1.93 (16.70 versus 14.77) life years (LYs) and an incremental cost of €15,453 mostly driven by treatment costs. The incremental cost-utility ratio (ICUR) was €7,553/QALY and the incremental cost-effectiveness ratio was €8,014/LY. The present evaluation suggest that, compared to a trastuzumab, trastuzumab emtansine seems to be a promising cost-effectiveness option for treating HER2+ adjuvant breast cancer in France. Results should be confirmed by using French adjusted utility values.

Pharmacological effects of the simultaneous and sequential combinations of trifluridine/tipiracil (TAS-102) and 5-fluorouracil in fluoropyrimidine-sensitive colon cancer cells.

The aim of this study was to investigate possible synergistic effects in vitro of trifluridine/tipiracil (TAS-102) and 5-fluoruracil (5-FU) on fluoropyrimidine-sensitive colon cancer cell lines of different mutational status in order to build a rational basis for the future use of this combination therapy in adjuvant settings or as a first-line treatment for metastatic disease. Proliferation assays were performed on HT-29 (B-raf mutated), SW-620 (ras mutated), and Caco-2 (wild type) colon cancer cell lines exposed to 120-h treatments of 5-FU, TAS-102 and their different combination schedules (simultaneous, sequential and reverse) at equimolar and non-equimolar ratios. The synergistic, additive and antagonistic effects of 5-FU and TAS-102 were determined by the combination index (CI) and dose reduction index (DRI). Our preclinical in vitro results may suggest an apparently counterintuitive but strongly synergistic combination of 5-FU and TAS-102 in fluoropyrimidine-sensitive colon cancer cells allowing a marked theoretical reduction in the administered doses of both drugs. In particular, this association seems to be highly effective in wild-type colon cancer cells, both in sequential and simultaneous schedules. Together, these data may build a rational basis for the future use of TAS-102 combined with 5-FU in adjuvant settings, or as a first-line treatment for metastatic disease.

Real life data from Turkey regarding the impact of first-line sunitinib and pazopanib in metastatic renal cell cancer.

e16075 Background: Although the distribution in the world varies widely, renal cell carcinoma (RCC) is the ninth most common cancer, especially in males. It’s the seventh most common cancer in Turkey. In this study, the progression-free survival (PFS) and overall survival (OS) of patients with metastatic RCC (mRCC) who were treated at 13 centers in our country were evaluated and the efficacy of first-line treatment approaches was compared. Methods: Data of mRCC patients admitted to 13 outpatient clinics in Turkey between 2008 and 2018 were reviewed retrospectively. Demographic characteristics, pre-treatment clinical evaluations, information about treatment approaches and survival outcomes of the patients were collected. All medical records were collected by a detailed review of the patients’ charts. The median and percentage values were frequently signified for defining of central trends. Kaplan-Meier method was applied for OS analyzes and log-rank test with Cox-regression models were applied for the evaluation of prognostic factors. Results: Data from files of 262 patients were reviewed. Twelve of these patients were excluded from the study because they could not receive treatment due to comorbidities and other reasons at metastatic stage of the disease. Of the patients, 100 (40%) were female and 150 (60%) were male. Median age was 60 (range 21-83). For the entire group, the median PFS (mPFS) was 27.6 months and the median overall survival (mOS) was 46.1 months. In terms of first-line treatment of metastatic disease, 41.3% of the patients received sunitinib, 48.8% of the patients received pazopanib, 15.8% of the patients received other treatments. PFS of the patients receiving sunitinib, pazopanib and the other treatments were 26.3 months, 34.2 months and 14.2 months, respectively. There was no statistically significant difference between PFS of the patients receiving sunitinib and pazopanib (p = 0.05). mOS was 54 months in sunitinib arm, 54.9 months in pazopanib arm and 23.3 months in the other treatment arm. There was no statistically significant difference between two treatment agents in terms of mOS (p = 0.43). Conclusions: Pazopanib was more commonly prescribed in Turkey. There were no statistically significant differences between mPFS and mOS of the patients who received sunitinib and pazopanib for the first-line treatment of mRCC. With increased use of immunotherapeutic agents for the first-line treatment of mRCC in our country, improvement in mOS could be expected.

Importance of vision for minimizing postural sway evidenced through a battery of simple standing balance tasks and a chest-worn accelerometer

The purpose of the present retrospective analysis was to describe the trends in exposure to multiple lines of treatment and overall survival (OS) in patients with metastatic renal cell carcinoma (mRCC) who started therapy in 2 different periods (period 1, 2004-2010; and period 2, 2011-2017).The proportion of patients who received subsequent lines of treatment after disease progression was compared between the 2 groups. OS was measured from the start of first-line treatment for metastatic disease to death or the last follow-up examination. Both univariate and multivariate analyses were performed.A total of 500 patients were included in the study; 274 started treatment in period 1 and 226 in period 2. Of those patients who stopped first-line treatment because of disease progression, the patients in period 2 had a greater conditional probability to receive second- and third-line treatment compared with patients in period 1 (77.2% vs. 63.7%; odds ratio [OR], 1.93; 95% confidence interval [CI], 1.20-3.11; P = .0065; and 69.6% vs. 48.1%; OR, 2.48; 95% CI, 1.40-4.40; P = .002, respectively). The median OS improved from 22.8 months for patients in period 1 to 38.2 months for patients in period 2 (univariate analysis: hazard ratio, 0.65; 95% CI, 0.50-0.83; P = .001).Patients who started treatment during the past 5 years were exposed to a greater number of treatment lines compared with patients treated before 2011. Our data suggest that the increase of treatment options available and clinician expertise could be associated with better outcomes.

Clinical and genomic alterations features of patients with advanced colitis associated cancers (CAC).

e15010 Background: CAC are a catastrophic complication of inflammatory bowel disease. The spectrum of genomic alterations (GA) in CAC is different than that of sporadic colorectal cancer (CRC) (Yaeger et al PMID 27063727). While the prognosis for CAC patients (pts) may be worse than that of sporadic CRC pts, there is little data regarding outcome for metastatic CAC pts treated with standard chemotherapy regimens. We reviewed demographic features and clinical outcome for pts with metastatic CAC in the context of somatic tumor GA. Methods: We identified small and large bowel CAC cases seen at Memorial Sloan Kettering between 2003 and 2015 with tissue available for study. Hybrid capture based next-generation sequencing analysis of over 300 cancer-related genes was used to comprehensively characterize GA. The electronic medical record of each patient was reviewed. Demographic and clinical data was extracted and outcome reviewed in the context of somatic tumor GA. Results: Clinical features for 17 pts with metastatic CAC are shown below. All pts with initial stage III CAC received FOLFOX adjuvant therapy. First-line treatment for metastatic disease included FOLFOX/FOLFIRINOX/FU-LV in 10 previously untreated pts and FOLFIRI after adjuvant therapy. Median duration of survival from time of metastatic disease was 14.8 months, (95% CI 5.7-24.3;range 2-68+ months), substantially less than that expected for pts with Stage IV CRC. Only 4 patients survived for &gt; 24 months. GA were identified in TP53 (87%) and KRAS (33%); potentially targetable alterations were found in 8 pts ( IDH1 (1), EML4-ALK(1), ERBB2 (1); FGFR1/2 (3); BRAF (1); PIK3CA(1). 2 pts received a targeted agent based on GA; 1 partial response to a FGFR inhibitor is ongoing. No patient had a hyper-mutated tumor. Conclusions: Metastatic CAC pts have an exceedingly poor prognosis, with survival well below that expected for sporadic CRC. BRAF mutations associated with poor outcome in sporadic CRC are rare in CAC. 47% of CAC pts had potentially targetable GA. [Table: see text]

Perivascular PDGFR-\u03b2 is an independent marker for prognosis in renal cell carcinoma

Background:Renal cell carcinoma (RCC) is a highly vascularised tumour, where anti-angiogenic treatment with multi-tyrosine-kinase-inhibitor, is used for first-line treatment of metastatic disease. Variations in vascular characteristics are likely to contribute to variations in intrinsic aggressiveness of the disease. Emerging studies are identifying perivascular status, including perivascular PDGFR-β, as a determinant of prognosis in other tumour types.Methods:This work explored the impact on prognosis of vascular characteristics in RCC through analyses of a population-based collection of tumours from surgery-alone-treated patients. The quantitative data from a panel of vascular metrics were obtained through computerised image analysis of sections double-stained for expression of the endothelial cell marker CD34 together with perivascular markers α-SMA or PDGFR-β.Results:Perivascular expression of PDGFR-β and α-SMA were positively correlated to each other, and negatively correlated to vessel density. High expression of PDGFR-β and α-SMA as well as low vessel density was significantly associated with short survival in uni- and multivariate analyses. Subgroup analyses demonstrated that the prognostic impact of the perivascular markers was particularly prominent in the T4-subgroup. A novel metric, related to PDGFR-β perivascular heterogeneity, was also associated with prognosis in uni-and multi-variate analyses. This novel metric also acted as a prognosis marker in ovarian cancer.Conclusions:The study demonstrates previously unrecognised associations between RCC survival and the absolute levels, and variability, of perivascular PDGFR-β. This marker should be further explored in other RCC cohorts. Findings also suggest mechanistic analyses and studies on the relationship between perivascular status and efficacy of multi-tyrosine-kinase-inhibitors.