Initiation Of First-line Chemotherapy Research Articles

The Gustave Roussy Immune score is a powerful biomarker for predicting therapeutic resistance to chemotherapy in gastric cancer patients.

It is highly important to be able to predict the therapeutic efficacy of chemotherapy on patients with unresectable advanced or recurrent gastric cancer (GC). The Gustave Roussy Immune Score (GRIm-s) is a predictor of therapeutic sensitivity to chemotherapy and immune checkpoint inhibitors (ICIs) in other cancers. The present study aimed to analyze the association of the GRIm-s with the therapeutic sensitivity of first-line chemotherapy in GC patients. We included 156 patients receiving primary chemotherapy treatment for unresectable or advanced recurrent GC between January 2012 and December 2021 at our institution. We evaluated the correlation between the GRIm-s and therapeutic sensitivities to chemotherapy. The GRIm-s was assessed before the start of first-line chemotherapy. Among the 156 patients, 138 (88.5%) and 18 (11.5%) were classified in the low- and high-risk groups, respectively. The GRIm-s high-risk group was significantly older (p = 0.013), had more advanced unresectable cancer (p = 0.0098), and was significantly less likely to progress to second-line chemotherapy (p = 0.014). The overall survival rate (OS) (p = 0.039) and the progression free survival rate (PFS) (p = 0.017) were significantly worse in the GRIm-s high-risk group. The high GRIm-s was an independent prognostic factor for poor survival in multivariate analysis (p = 0.0094). Focusing on the GRIm-s before first-line chemotherapy initiation for unresectable advanced or postoperative recurrent GC was useful in predicting the therapeutic resistance to chemotherapy, transition to second-line chemotherapy, and poor prognosis.

Clinical Outcomes of Enfortumab Vedotin in Advanced Urothelial Carcinoma With Prior Avelumab Versus Pembrolizumab Therapy.

This study retrospectively evaluated whether enfortumab vedotin (EV) monotherapy is effective as a late-line treatment according to prior treatment type in patients with advanced urothelial carcinoma (UC). We assessed consecutive patients from the Uro-Oncology Group in the Kyushu study population with lower and upper urinary tract cancer treated with EV monotherapy after platinum-based chemotherapy and immune checkpoint inhibitor therapy failure between December 2021 and March 2024. In particular, patients receiving avelumab maintenance or pembrolizumab therapy before EV for advanced UC were analyzed and compared according to the response rate, progression-free survival (PFS), and overall survival (OS). Of the 80 enrolled patients, 31 and 49 received avelumab and pembrolizumab before EV therapy, respectively. The avelumab and pembrolizumab groups had comparable objective response rates (48.4% vs. 44.9%, p=0.820) and disease control rates (77.4% vs. 67.3%, p=0.448). These two groups showed no significant difference in PFS from the initiation of EV (median: 6.4 months vs. 4.2 months, p=0.184); meanwhile, the avelumab group had better OS from the initiation of EV than the pembrolizumab group (median: 16.0 months vs. 10.2 months, p=0.019). Moreover, the median OS after first-line chemotherapy initiation was longer in the avelumab group than in the pembrolizumab group (40.3 months vs. 24.7 months, p=0.054). On multivariate analysis, avelumab maintenance therapy before EV reduced the mortality risk by 47% (95% confidence interval=0.27-1.03; p=0.059). EV monotherapy after avelumab maintenance therapy provides favorable survival outcomes in patients with advanced UC.

Prognosis and conditional survival among women with newly diagnosed ovarian cancer

ObjectiveAn important question in determining long-term prognosis for women with ovarian cancer is whether risk of death changes the longer a woman lives. Large real-world datasets permit assessment of conditional survival (CS) given both prior overall survival (OS) and real-world progression-free survival (rwPFS). MethodsUsing a longitudinal dataset from US oncology centers, this study included 6778 women with ovarian cancer. We calculated CS rates as the Kaplan-Meier probability of surviving an additional 1 or 5 years, given no mortality (OS) or disease progression (rwPFS) event in the previous 0.5–5 years since first-line chemotherapy initiation, adjusted for factors associated with OS based on multivariable Cox regression. ResultsMedian study follow-up was 9 years (range, 1–44) from first-line initiation to data cutoff (17-Feb-2021). Median OS was 58.0 months (95% CI, 54.9–60.8); median rwPFS was 18.4 months (17.4–19.4). The adjusted 1-year CS rate (ie, rate of 1 year additional survival) did not vary based on time alive, whereas the adjusted 5-year CS rate increased from 48.5% (47.0%–50.1%) for women who had already survived 6 months to 66.4% (63.3%–69.6%) for those already surviving 5 years (thus surviving 10 years total). The adjusted 1-year CS rate increased from 90.4% (89.5%–91.4%) with no rwPFS event at 6 months to 97.6% (96.4%–98.8%) with no rwPFS event at 5 years; adjusted 5-year CS rate increased from 53.7% (52.0%–55.5%) to 85.0% (81.2%–88.9%), respectively. ConclusionsThis analysis extends the concept of CS by also conditioning on time progression-free. Patients with longer rwPFS experience longer survival than patients with shorter rwPFS.

Clinical features of germline BRCA1/2 or ATM pathogenic variant positive pancreatic cancer in Japan

BackgroundThere has been increasing interest into the role of germline BRCA1/2 pathogenic variants (gBRCA PV) and gATM PV and likely PV (PV and LPV; PV + LPV) in the carcinogenesis and treatment of pancreatic cancer (PC), but the clinical features have not been well described. MethodsPatients with confirmed gBRCA PV and gATM PV + LPV PC treated at our hospital between April 2016 and December 2021, were retrospectively evaluated for clinical characteristics and outcomes. ResultsTwenty-two patients harbored gBRCA PV and three patients harbored gATM PV + LPV. Of the gBRCA PV patients, 81.8 % received platinum-based chemotherapy with favorable treatment outcomes with an objective response rate of 50.0 % (95 % CI: 23.0–77.0), median progression free survival (PFS) of 334 days, and median overall survival (OS) of 926 days from the initiation of first-line chemotherapy. The annual number of patients with gBRCA PV was two patients per year before January 2021 (when BRACAnalysis became available in Japan), and ten patients during the 10 months thereafter. Four patients (20 %) with gBRCA PV developed soft-tissue metastasis with progression. Two patients with gATM PV + LPV received platinum-based chemotherapy and the best response of those patients was partial response and stable disease and their OS from the initiation of first-line chemotherapy was 1192 and 989 days, and PFS was 579 and 140 days, respectively. ConclusionThe diagnosis of gBRCA PV-positive PC has increased revealed in recent years. These tumors appear to be sensitive to platinum-based chemotherapy, with long term survival observed in gATM PV + LPV-positive patients.

Prognostic significance of the cachexia index in patients with unresectable advanced gastric cancer receiving palliative chemotherapy: a retrospective single-center study.

To investigate the prognostic utility of the cachexia index (CXI) in unresectable advanced gastric cancer (UAGC). The relationship between CXI and the outcomes was evaluated in 102 patients with UAGC who had received first-line palliative 5-fluorouracil-based chemotherapy between January 2012 and December 2021. The median survival time (MST) from first-line chemotherapy initiation was 16.2months, and the cohort included 60 and 42 patients with high and low CXIs, respectively, based on the optimal CXI cutoff. The rates of patients with a performance status score of 0, recurrence, third-line chemotherapy, and all grade 3-4 side effects, including febrile neutropenia (FN), were significantly higher in the CXIhigh group than in the CXIlow group. The prognosis based on MST was significantly better in the CXIhigh group than in the CXIlow group (22.5 vs. 11.6months, p < 0.001). According to a multivariate analysis, a low CXI and performance status score of 1-2 were poor prognostic factors. Patients with UAGC and a low CXI had poorer prognoses and more frequent grade 3-4 side effects, including FN, than those with a high CXI. Patients with UAGC and a low CXI should be carefully managed to control for side effects to receive subsequent treatment.

The Glasgow Prognostic Score Predicts Survival Outcomes in Patients with Extensive-Stage Small Cell Lung Cancer

Introduction: The Glasgow prognostic score (GPS) is an inflammation-related score based on C-reactive protein and albumin concentrations. Few studies have assessed the correlation between the GPS and the efficacy of chemotherapy in patients with extensive-stage small cell lung cancer (ES-SCLC). Therefore, this study aimed to evaluate the utility of the GPS in predicting the survival outcomes of patients with ES-SCLC. Methods: This retrospective study evaluated patients with ES-SCLC who had undergone chemotherapy between February 2008 and November 2021. GPS values were evaluated before the initiation of first-line chemotherapy. The Kaplan-Meier method and Cox proportional hazards models were used to assess progression-free survival (PFS) and overall survival (OS). Results: The GPS values of the 113 patients were zero (54 patients, 48%), 1 (37 patients, 33%), and 2 (22 patients, 19%). The median follow-up duration was 10.7 months. Median PFS was 6.2, 5.6, and 3.8 months in the GPS 0, 1, and 2 groups, respectively, suggesting that the GPS zero group had a significantly more favorable PFS than the GPS 2 group (p < 0.001). Median OS was 17.1, 9.4, and 5.6 months in the GPS 0, 1, and 2 groups, respectively, suggesting that the GPS zero group had a significantly more favorable OS than the GPS 2 group (p = 0.001). Multivariate analysis confirmed that a GPS of 2 independently predicted unfavorable PFS (hazard ratio [HR], 2.89; 95% confidence interval [CI]: 1.68–4.88; p < 0.001) and OS (HR, 3.49 [95% CI: 1.83–6.63], p < 0.001). Conclusion: The study’s findings suggest that the GPS can predict the survival outcomes of patients with ES-SCLC who have undergone chemotherapy. The GPS is an easy-to-calculate biomarker and would be ideal for routine use in clinical settings.

Antibiotic exposure around first line chemotherapy and survival in ovarian cancer (347)

<b>Objectives:</b> To assess whether exposure to antibiotics (ABX) in the 90 days preceding initiation through the completion of first-line chemotherapy for epithelial ovarian carcinoma (EOC) is associated with decreased overall survival (OS) and truncated treatment-free interval (TFI), which we hypothesized. <b>Methods:</b> A retrospective cohort study of women with newly diagnosed stage III/IV EOC between 2009 to 2019 treated at a single institution was conducted. ABX exposure of >48 hours, timing with respect to chemotherapy initiation, and ABX class were captured. The association of ABX with TFI and OS was assessed with univariate and multivariable Cox proportional hazard models. <b>Results:</b> Of the 360 eligible women, 47% (<i>n</i>=170) were exposed to antibiotics, with 12% (<i>n</i>=46) receiving them only prior to first-line chemotherapy initiation, 23% (<i>n</i>=81) receiving them during chemotherapy, and 12% (<i>n</i>=43) receiving them before and during chemotherapy. Exposure to any ABX was associated with a decreased median OS (42.1 vs 60.0 months, HR: 1.33, 95% CI: 1.02-1.73, p=0.03) compared to no ABX. On subset analyses, ABX, specifically during chemotherapy, was associated with a decreased median OS (42.2 vs 60.0 months, HR: 1.46, 95% CI: 1.01-2.10). While exposure to ABX as a whole was not associated with TFI, receipt of ABX before chemotherapy was associated with a decreased TFI, with an HR of 1.76 (95% CI: 1.00-3.11, p=0.05), when compared to no ABX. Treatment with antibiotics against gram-positive organisms (GPO) with vancomycin, lin- cosamides, and macrolides was associated with worse OS (HR: 1.49, 95% CI: 1.01-2.20, p=0.049). In a multivariable analysis accounting for bowel surgery, exposure to granulocyte colony-stimulating factor, and IP chemo administration, exposure to ABX remained associated with an increased risk of death (HR: 1.38, 95% CI: 1.02-1.68, p=0.039). <b>Conclusions:</b> Patients with stage III/IV EOC exposed to ABX 90 days prior to chemotherapy had statistically significantly worse TFI compared to unexposed patients. In contrast, patients exposed to ABX during chemotherapy had worse OS compared to unexposed patients. Treatment with ABX targeting GPO decreased OS. Efforts to decrease the need for ABX, such as judicious prescription of ABX and implementation of perioperative infection prevention bundles, may offer an opportunity to increase survival in EOC.

Patterns of use and outcomes of adjuvant bevacizumab therapy prior to regulatory approval in women with newly diagnosed ovarian cancer

We used real-world claims data to assess the utility of the relatively novel therapeutic bevacizumab in patients with newly diagnosed ovarian cancer in the United States after release of clinical data but prior to FDA approval. We used the IQVIA Pharmetrics Plus commercial claims database to identify women with a new diagnosis of ovarian cancer who underwent primary surgery or neoadjuvant chemotherapy followed by interval surgery from 2006 to 2018. We calculated the rate of use of bevacizumab, and the relative frequency of hospital and emergency department (ED) admissions. Treatment-related toxicities, and time to second line chemotherapy were calculated. Among 8923 women who met study parameters, 533 (6.0%) received bevacizumab. The rate of use increased over time from 1.5% in 2006 to 7.0% in 2017 (P < 0.001), with a peak of 8.6% in 2011. The use was lowest in those ≥ 70years old (2.8%), and in the West (4.5%), and was unaffected by number of comorbidities. Over one third (35.1%) received bevacizumab for less than 3 months, and 15.9% remained on it for greater than 13months. Bevacizumab use was not associated with hospitalization or ED admission. Toxicities included hypertension (15.0%), kidney damage (6.8%), bleeding (3.8%), venous thrombo-embolism (2.3%) and fistula (1.1%). Time from initiation of first line chemotherapy to initiation of second line therapy was 19.9months without bevacizumab and 22.6months with bevacizumab use. Real-world patterns of upfront bevacizumab use prior to FDA approval in 2018 differed significantly from trial data.

Eribulin improved the overall survival from the initiation of first-line chemotherapy for HER2-negative advanced breast cancer: a multicenter retrospective study

BackgroundEribulin methylate (eribulin) improved the overall survival (OS) of eribulin-treated patients with HER2-negative advanced breast cancer (ABC) in prospective and retrospective studies. However, the effect of eribulin on OS as first-line chemotherapy and the characteristics of the patients who benefited from eribulin remain unclear.MethodsBetween January 2011 and December 2016, 301 patients with HER2-negative ABC who started first-line chemotherapy at 3 institutions were retrospectively evaluated for OS from the initiation of first-line chemotherapy.ResultsWe identified 172 patients (119 estrogen receptor-positive [ER+], 47 ER−, 6 unknown) who received eribulin (eribulin group) and 129 patients (92 ER+, 31 ER−, 6 unknown) who did not receive eribulin (non-eribulin group). The median OS from the initiation of first-line chemotherapy in the two groups was not statistically significant (869 vs. 744 days, P = 0.47, log-rank); however, in patients who received eribulin in later lines (≥3rd-line) and who had a history of perioperative chemotherapy with anthracycline- and/or taxane-based regimens, the median OS improved (1001 vs. 744 days, P = 0.037; and 834 vs. 464 days, respectively P = 0.032, respectively; Wilcoxon). Multivariate analyses revealed that a history of perioperative chemotherapy with anthracycline- and/or taxane-based regimens was a predictive factor (hazard ratio, 0.39; 95% confidence interval, 0.21–0.70) for OS.ConclusionsThis study successfully identified subgroups of HER2− ABC patients with improved OS by eribulin therapy. Selecting patients according to their background and line of treatment will maximize the efficacy of eribulin therapy.

Feasibility of using a computerized food frequency questionnaire (FFQ) to assess dietary patterns in patients with advanced gastrointestinal (GI) malignancies.

465 Background: Identification of poor dietary patterns is important for the optimal management of patients with metastatic GI malignancies who suffer from high rates of malnutrition and sarcopenia which are associated with increased rates of treatment-related toxicity and worsened survival. Dietary records or recall methods and FFQs are available but have high patient burden and are seldom utilized in oncology settings outside of formal nutritional consultations. Thus, we evaluated the feasibility of conducting serial assessments of dietary patterns using a novel computerized FFQ technology. Methods: Assessments of diet using the computerized FFQ, nutritional status (NUTRISCORE), QOL and anorexia/cachexia burden (FAACT), anxiety/depression (HADS) and taste burden were done at the time of initiation of first-line chemotherapy (baseline) and 3 months later. The FFQ was done independently either at home on personal computer after visit or via iPad in infusion room. Dietary quality was defined by the Healthy Eating Index 2010 (HEI) score, which was automatically calculated by the computerized FFQ software. Feasibility was defined as at least 70% of patients completing baseline and 3-month assessments. Spearman’s correlations were used to determine associations between measures. Results: 29 patients with advanced (metastatic or unresectable) GI cancers were enrolled and 23 completed the baseline FFQ (8 colorectal, 5 pancreas, 5 gastroesophageal, 5 other). Median age was 58 (20-78) with M:F ratio of 10:13. The overall completion rate of baseline and 3-month assessments was 81.8%, meeting the pre-defined feasibility criteria. The mean baseline HEI score was 65 (range 38-88). Of patients who completed both baseline and 3-month assessments, the mean HEI score remained stable at 58 with changes in specific HEI components including a 20% decline in the seafood and plant protein score and a 13% decline in the whole grain score and small improvements in other areas (e.g. empty calories, dairy). There were no significant correlations between baseline HEI score and other assessments. Conclusions: It is feasible to use a computerized FFQ to assess for longitudinal changes in eating patterns and dietary quality in patients with advanced GI cancers, particularly when patients can complete the assessments during chemotherapy infusions. Preliminary findings also suggest that the FFQ can be helpful for highlighting areas in which diet quality could be improved. Additional analysis of other computerized FFQ data (e.g. macro/micronutrient consumption) is ongoing.

450P The impact of late-line treatment on overall survival (OS) from the initiation of first-line chemotherapy (CT) for patients (pts) with metastatic colorectal cancer (mCRC): Updated analysis

450P The impact of late-line treatment on overall survival (OS) from the initiation of first-line chemotherapy (CT) for patients (pts) with metastatic colorectal cancer (mCRC): Updated analysis

Real-World Assessment of Health Care Costs for Patients with Metastatic Pancreatic Cancer Following Initiation of First-Line Chemotherapy.

Management of metastatic pancreatic ductal adenocarcinoma (mPDA) places a significant financial burden on the U.S. health care system because of such factors as treatment with multidrug chemotherapy regimens, management of chemotherapy-related adverse events, and disease- or treatment-related hospitalizations. Depending on functional status, first-line chemotherapy regimens that are guideline recommended include nab-paclitaxel with gemcitabine (AG) and FOLFIRINOX (FFX), the combination of fluorouracil, leucovorin, irinotecan, and oxaliplatin. However, few previous studies have examined overall health care costs associated with mPDA management. To describe health care costs following initiation of first-line treatment with AG or FFX among patients with mPDA. Retrospective cohorts of first-line AG and FFX initiators were constructed from the MarketScan database (2014-2017). The index date was the date of first-line AG or FFX initiation. Included patients had insurance enrollment for 6 months before the index date. Total cumulative health care costs and costs from outpatient services, inpatient admissions, emergency department visits, chemotherapy administrations, and pharmacy dispensing were assessed within 12 months after the index date (i.e., 0-1, 0-2, …, 0-12 months). Patient-level cost data began accruing from the first paid claim and continued accruing until the censoring date. A total of 2,199 patients with mPDA initiated first-line AG (n = 1,352) or FFX (n = 847). Compared with AG initiators, FFX patients were younger (mean age 59 vs. 63 years) and had better baseline health status, with fewer having diabetes (43% vs. 57%) or coronary artery disease (12% vs. 22%). Median follow-up was 5.4 and 7.2 months for AG and FFX, respectively. Median first-line treatment duration was 2.1 months with AG and 2.3 months with FFX. Six months following first-line treatment initiation, total cumulative health care costs (median) were $85,714 (95% CI = $79,683-$91,788) and $114,116 (95% CI = $105,816-$119,591) for AG and FFX initiators, respectively. Outpatient services contributed the largest fractional cost for both groups. Total health care costs for patients with mPDA who initiated FFX or AG are driven mostly by outpatient rather than inpatient costs. Further research, using comparative methodology, is warranted to fully understand cost drivers and whether higher costs for FFX patients relate primarily to use of FFX or higher underlying use of outpatient care among FFX patients. This study was funded by Halozyme Therapeutics. Oestreicher and Yeganegi were employees of Halozyme Therapeutics at the time of the study and were involved in study design, data interpretation, and the decision to submit the data for publication. Bullock reports advisory board fees from Eisai, Exelixis, Bayer, and Taiho and consulting fees from Halozyme Therapeutics, outside the submitted work. Rowan reports consulting fees from Halozyme Therapeutics, during the conduct of the study. Chiorean reports grants and consulting fees from Celgene and Halozyme Therapeutics; grants from Lilly, Stemline, Ignyta, Roche, Merck, Boehringer-Ingelheim, Bristol Meyer Squibb, Incyte, Macrogenics, Rafael, and AADi; and consulting fees from Astra Zeneca, Array, Eisai, Ipsen, Five Prime Therapeutics, Seattle Genetics, Vicus, and Legend, outside the submitted work.

Body Mass Index and Weight Loss in Metastatic Colorectal Cancer in CALGB (Alliance)/SWOG 80405.

BackgroundIn nonmetastatic colorectal cancer, overweight and mild-to-moderately obese patients experience improved outcomes compared with other patients. Obesity’s influence on advanced or metastatic colorectal cancer (mCRC) is relatively unexplored.MethodsWe conducted a prospective body mass index (BMI) companion study in Cancer and Leukemia Group B (now Alliance)/SWOG 80405, a phase III metastatic colorectal cancer (mCRC) treatment trial. BMI was measured at trial registration. Primary and secondary endpoints were overall and progression-free survival, respectively. To minimize confounding by poor and rapidly declining health, we used Cox proportional hazards regression to adjust for known prognostic factors, comorbidities, physical activity, and weight loss during the 6 months prior to study entry. We also examined weight loss prior to enrollment as an independent predictor of patient outcome. All statistical tests were two-sided.ResultsAmong 2323 patients with mCRC, there were no statistically significant associations between BMI and overall or progression-free survival (adjusted Ptrend = .12 and .40, respectively). Weight loss during the 6 months prior to study entry was associated with shorter overall and progression-free survival; compared with individuals with stable weight ±4.9%, individuals with weight loss greater than 15% experienced an adjusted hazard ratio of 1.52 for all-cause mortality (95% confidence interval [CI] = 1.26 to 1.84; Ptrend < .001) and of 1.23 for disease progression or death (95% CI = 1.02 to 1.47; Ptrend = .006).ConclusionsIn this prospective study of patients with mCRC, BMI at time of first-line chemotherapy initiation was not associated with patient outcome. Weight loss prior to study entry was associated with increased risk of patient mortality and disease progression.

Impact of progression at baseline and on-treatment progression events in three large prostate cancer trials

BackgroundThere is a discussion about the optimal timing to initiate or switch treatment in metastatic castration-resistant prostate cancer (mCRPC). This post hoc analysis of 3 large trials for men with mCRPC examined the influence of the type of progression at initiation of first-line chemotherapy, as well as the type of progression during treatment, on treatment outcomes. MethodsData from the phase III studies VENICE (n = 1224), TAX327 (n = 1006) and FIRSTANA (n = 1168) were used as independent data sets. Type of progression was defined as follows: prostate-specific antigen (PSA) only (group 1), radiological (±PSA) (group 2) or pain (±PSA, ± radiological) progression (group 3). The impact of baseline type of progression on overall survival (OS) was evaluated in multivariate Cox regression analysis with backward elimination, stratified for the Eastern Cooperative Oncology Group performance score and treatment arm. ResultsThe median OS (arms combined) from treatment initiation in VENICE was 28.6, 26.3 and 16.9 months for G1, G2 and G3, respectively (hazard ratio: 1.14 [95% confidence interval {CI}: 0.92–1.41%] in G2 and 2.13 [95% CI: 1.75–2.59%] in G3 compared with G1). Multivariate analysis (arms combined) showed that pain progression at baseline was an independent predictor of poor OS. Similar findings were observed in the TAX327 and FIRSTANA data sets. During treatment, pain or radiological progression preceded PSA progression in ~55% of the patients. The retrospective characteristic of this study is a limitation. ConclusionsThe type of progression at baseline strongly predicts OS in men with mCRPC treated with first-line chemotherapy. During treatment, pain and/or radiological progression preceded PSA progression as the first progression event in ~55% of the patients. This finding has the prospect to be incorporated in clinical guidelines and to be practice changing because it implies the need for regular imaging and not to rely on PSA progression alone.

Impact of Socioeconomic Factors on Timeliness of First Line Chemotherapy and Survival in Patients with Active Multiple Myeloma

Background Multiple myeloma is a common hematological malignancy. In 2016, there were an estimated 131,392 people living with myeloma in the United States and accounted for 2% of all cancer related deaths. Studies among cancer patients have repeatedly demonstrated that sociodemographic factors impact timeliness of treatment and in turn, survival (Kelly et al. Blood,2016). The treatment options in multiple myeloma are variable and may involve stem cell transplant , chemotherapies and biological therapies. We hypothesized that sociodemographic factors impact the time to initiation of first line chemotherapy in patients with multiple myeloma. We also explored if these factors influenced outcomes. Methods We queried the National Cancer Database for patients with multiple myeloma (ICD-0-3 code 9732) diagnosed from 2004-2016. We excluded patients who were considered for stem cell transplant or other modalites to include only those who received chemotherapy as first line treatment. Active myeloma patients were defined as those who were treated within 3 months (120 days) of diagnosis based on similar methodology in previous studies (Ravindran et al. Blood Cancer J,2016). Time to initiation (TTI) was defined as time in days (d) from diagnosis to initiation of systemic chemotherapy.Survival was measured in terms of months (m) from the day of diagnosis. Stepwise negative binomial regression and Cox proportional hazard models were used for analysis. Results Of 160,900 patients with multiple myeloma, we identified 71,523 patients meeting the eligibility criteria. Median age was 68 (range 21-90) years and 55% were males. Median TTI was 19d (range 0-120d) and median overall survival was 34 months. Even though the TTI increased from 24d (2004) to 27d (2016) this was not significant when other variables were adjusted. The overall median survival improved by 10 months between 2004 and 2012 (28 months to 37 months). Determinants of increased TTI in a multivariate model included African American race (p-value &lt;0.005), not living in Urban area (p-value=0.02), having less comorbidities (p-value&lt;0.0005), being treated at an academic or research program (p-value&lt;0.0005) and are described in Table 1. Factors impacting survival in a multivariate model included year of diagnosis (p-value&lt;0.0005) and age (p-value&lt;0.0005) - positive relation, time to treatment (negative relation, p-value&lt;0.0005-Figure 1), race (Caucasians-32m vs. African Americans-38m, p-value&lt;0.0005), insurance status (Government-28m vs. Private-48m, p-value&lt;0.0005), socioeconomic status (lowest-32m vs. highest-37m, p-value=0.003), comorbidities (lowest-38m vs. highest-15m, p-value&lt;0.0005) , treatment facility (Comprehensive Community Cancer Center-31m vs. Academic Research Program-38m) and are described in Table 2. Conclusion The findings of the present study are twofold. First, while not as pronounced as in other cancer cohorts, disparities do exist in timeliness to chemotherapy initiation. The longer TTI in academic centers is interesting but may reflect a more complicated patient population. Second, shorter time to therapy does not necessarily lead to improved outcome, likely reflecting high risk features not captured by standard assessments. This is similar to other studies in hematological malignancies and supports the proposition that clinical trials should accommodate patients who need urgent therapy to detect treatment effects in high‐risk groups (Olszewski et al. Br J Hem,2018). Disclosures No relevant conflicts of interest to declare.

610P - Prognostic significance of circulating regulatory T lymphocytes (Tregs) in patients with metastatic colorectal cancer (mCRC) under treatment with first-line chemotherapy

BackgroundIn humans Tregs lack a unique phenotypic marker and Foxp3 expression in cluster of differentiation (CD) 4+CD25+ or CD4+CD25high T lymphocytes is commonly used for their characterization. In early colorectal cancer, the presence of Tregs in CRC tumour tissue has been associated with favourable prognosis. However, the prognostic role of circulating Tregs in CRC patients and especially in the metastatic setting is not yet clear. MethodsWe collected peripheral blood from 57 patients with mCRC before initiation of first line chemotherapy. Samples were analysed with multicolour flow cytometry using monoclonal antibodies against CD3, CD4, CD25, and FoxP3. The ratio of FoxP3 positive cells within the CD3+CD4+CD25high lymphocytic subpopulation (F/H ratio) was measured and quartile analysis according to this ratio was carried out. Overall survival was calculated from initiation of first line chemotherapy to death or last follow up. Median OS (mOS) was compared between the highest quartile and the rest using the Breslow (Generalized Wilcoxon) method. Ratios were compared between groups with the Mann Whitney U-test. Statistics were analyzed with SPSS and flow cytometry data with Kaluza 2.1. ResultsThe median F/H ratio was 0,08 (Interquartile range 0,018-0,34) with a distribution skewed to the right (range 0 to 0.85). For each quartile mOS is shown in the table. The mOS for the highest quartile was 8 months (m) (95% Confidence Interval(CI) 0 - 20.6m) and 25m for the rest (95% CI 18.2m-31.8m)(p=0.03). No difference was observed in F/H ratio in different groups according to KRAS/NRAS mutations’ status, prior adjuvant chemotherapy, performance status or sidedness of primary site.Table610PTableQuartileF/H ratio (range)nmOS (m)mOS(m)p1st0-0,0181424252nd0,0181-0,0815343rd0,0810-0,3415244th0,3410-0,851380.03 ConclusionsThe F/H ratio in patients with mCRC is spread over a wide range of values with the majority below 0.1. High values (>0.34) seem to have prognostic significance and be associated with worse outcome. Legal entity responsible for the studyMedical School, University of Crete. FundingHellenic Oncology Research Group, Medical School, University of Crete. DisclosureZ. Zafeiriou: Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Sanofi; Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Roche; Travel / Accommodation / Expenses: Bristol. A. Koutoulaki: Full / Part-time employment: Genesis Pharma. V. Georgoulias: Travel / Accommodation / Expenses: Sanofi. All other authors have declared no conflicts of interest.

587P - The impact of late-line treatment on overall survival (OS) from the initiation of first-line chemotherapy (CT) for patients (pts) with metastatic colorectal cancer (mCRC)

BackgroundFor the past 20 years, the improvement in OS has been achieved in mCRC. Active agents including anti-VEGF and anti-EGFR antibodies have contributed to this progress. Late-line treatment with regorafenib (REGO) or trifluridine/tipiracil (FTD/TPI) has also been demonstrated to be effective and these drugs are widely used as standard CT. However, no study has reported to what extent the availability of these two drugs changes the total OS of patients that is measured from the initiation of first-line CT. MethodsWe retrospectively enrolled consecutive mCRC pts at 3 institutions who received first-line CT between Jan 2005 and Sep 2016. We divided the pts into 3 groups according to the availability of drugs at the initiation of first-line CT; pts who started CT between Jan 2005 and Dec 2006 (cohort A: only cytotoxic drugs were available), between Jan 2007 and Dec 2011 (cohort B: anti-VEGF and anti-EGFR antibody were available), or between Jan 2012 and Sep 2016 (cohort C: REGO and FTD/TPI were available). Treatment outcomes were compared among the cohort A, B, and C. ResultsA total of 1,426 pts were analyzed. Pts characteristics of the cohort A (165 pts), B (626 pts), and C (635 pts) were as follows: median age, 62/64/65 years; ECOG PS≥2, 8.5%/8.8%/8.2%; right-sided primary, 26.1%/29.4%/29.9%; tumor grade Grade 3, 10.1%/13.1%/11.9%; KRAS mutation, 28.6%/38.4%/41.1%; and number of metastatic sites ≥2, 63.6%/61.3%/58.1%. In the cohort A, B, and C, 1.2%, 10.7%, and 31.2% of the pts received at least one of late-line treatment with REGO or FTD/TPI. Median OS of the cohort A, B, and C was 18.6 month (M), 25.3 M, and 27.2 M. Hazard ratio (HR) of death was 0.82 (95% confidential interval [CI], 0.68-0.98; p=0.0309) for the cohort B vs A, and 0.71 (95% CI, 0.59-0.86; p=0.0004) for the cohort C vs A, and 0.87 (95% CI 0.77-0.99; p=0.0356) for the cohort C vs B. ConclusionsThis real-world data analysis indicates that late-line treatment with REGO or FTD/TPI could contribute to the prolongation of OS from the initiation of first-line CT for mCRC pts. Legal entity responsible for the studyThe authors. FundingHas not received any funding. DisclosureT. Masuishi: Honoraria (self): Taiho Pharmaceutical, Merck Serono, Chugai Pharma, Yakult Honsha, Takeda, Eli Lilly, Bayer Yakuhin, Sanofi; Research grant / Funding (self): Yakult Honsha. Y. Kawamoto: Honoraria (self): Taiho Pharmaceutical, Daiichi Sankyo, Takeda Pharmaceutical, Chugai Pharmaceutical, Merck Biopharma, Eli Lilly. S. Yuki: Honoraria (self): Chugai Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., Bristol-Myers Squibb Co., Ltd., Eli Lilly Japan K.K., Bayer Yakuhin Co., Ltd., Taiho Pharmaceutical Co., Ltd., Ono Pharmaceutical Co., Ltd., Sanofi K.K., Pharma International Inc., Yakult H. Y. Komatsu: Honoraria (self): Taiho, Chugai, Yakult, Daiichi Sankyo, Bayer, Merck, Takeda; Research grant / Funding (institution): Taiho, Chugai, Yakult, Daiichi Sankyo, Bayer, Merck, Takeda. K. Muro: Honoraria (self): Takeda, Chugai Pharma, Yakult Honsha, Merck Serono, Taiho Pharmaceutical, Lilly, Ono Pharmaceutical, Bayer; Research grant / Funding (self): Ono Pharmaceutical, MSD, Daiichi Sankyo, Shionogi, Kyowa Hakko Kirin, Gilead Sciences, Merck Serono, Pfizer, Sanofi. T. Yamanaka: Honoraria (self): Chugai, Takeda, Taiho, Boehringer-Ingelheim, Bayer, Pfizer; Advisory / Consultancy: Gilead Sciences, Daiichi-Sankyo, Sysmex, Huya Biosciences; Honoraria (institution): Chugai, Takeda, Taiho, Boehringer-Ingelheim, Bayer, Daiichi-Sankyo, Ono, Merck Serono, Astellas, Eli Lilly. K. Yamazaki: Honoraria (self): Chugai Pharma, Daiichi Sankyo, Yakult Honsha, Takeda, Bayer, Merck Serono, Bristol-Myers Squibb Japan, Taiho Pharmceutical, Lilly, Sanofi, Ono Pharmaceutical, MSD; Research grant / Funding (institution): Taiho Pharmaceutical. All other authors have declared no conflicts of interest.

Abstract 3285: Body mass index, weight loss, and progression and mortality in metastatic colorectal cancer: Results from CALGB/SWOG 80405 (Alliance)

Abstract Background: In non-metastatic colorectal cancer, a body mass index (BMI) paradox is observed where overweight and early obese patients experience improved outcomes compared to patients with normal, low, or morbidly obese BMI. The influence of obesity on patients with advanced or metastatic colorectal cancer (mCRC) is relatively unexplored. Methods: We conducted a prospective BMI companion study in CALGB (now Alliance for Clinical Trials in Oncology)/SWOG 80405, a phase III mCRC treatment trial. BMI was measured at trial registration. Primary and secondary endpoints were overall and progression-free survival, respectively. To minimize confounding by poor and rapidly declining health, we used Cox proportional hazards regression to adjust for known prognostic factors, comorbidities, physical activity, and weight loss, and excluded individuals with low BMI &amp;lt;21 from statistical tests for trend. We also examined self-reported weight loss over the six months prior to trial enrollment as an independent predictor of patient outcome. Results: In this sub-study of a phase III mCRC trial, BMI was recorded for all 2,323 patients enrolled. Following adjustment for confounders, there were no significant associations between BMI and overall or progression-free survival (excluding BMI &amp;lt;21, Ptrend with increasing BMI = 0.12 and 0.42, respectively). Conversely, weight loss prior to treatment was associated with shorter overall and progression-free survival; compared to individuals with weight change &amp;lt;5%, individuals with weight loss &amp;gt;20% experienced an adjusted hazard ratio of 1.46 for all-cause mortality (95% confidence interval 1.15 to 1.85, Ptrend &amp;lt;.0001) and of 1.27 for disease progression or death (95% confidence interval 1.04 to 1.56, Ptrend = .009). Conclusion: In this prospective study of patients with mCRC, BMI at time of first-line chemotherapy initiation was not associated with patient outcome. Weight loss prior to study entry was associated with increased risk of patient mortality and disease progression. Citation Format: Brendan Guercio, Sui Zhang, Alan P. Venook, Fang-Shu Ou, Donna Niedzwiecki, Heinz-Josef Lenz, Federico Innocenti, Hanna Sanoff, Michelle R. Mahoney, Bert H. O'Neil, James E. Shaw, Blase N. Polite, Howard S. Hochster, James N. Atkins, Richard M. Goldberg, Robert J. Mayer, Charles D. Blanke, Charles S. Fuchs, Jeffrey A. Meyerhardt. Body mass index, weight loss, and progression and mortality in metastatic colorectal cancer: Results from CALGB/SWOG 80405 (Alliance) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 3285.

Does the extent of brain metastasis affect outcome of non-small cell lung cancer patients treated with chemotherapy?

e20616 Background: More than one third of advanced non-small cell lung cancer (NSCLC) patients (pts) experience brain metastases in the course of their disease. Although the outcome of NSCLC pts with brain metastasis is generally poor, identifying subgroups of pts that could benefit from appropriate therapeutic approach is clinically important, particularly in EGFR tyrosine kinase inhibitor (TKI) era. Methods: A retrospective review was conducted on 85 NSCLC pts with synchronous brain metastasis who underwent at least first-line chemotherapy, after treatment (Tx) for brain metastasis (gamma knife surgery or fractionated stereotactic radiotherapy : 42, whole brain radiation therapy : 38, surgical resection : 1, and no Tx : 4) from Jan 2002 to Dec 2013. Overall survival (OS) of all pts was analyzed according to the clinicopathological characteristics, Tx modality for brain metastasis, and chemotherapy. Results: The median OS for all pts after the initiation of first-line chemotherapy was 9 months. In univariate analysis, pts who received TKI (13 months versus 6 months, p= 0.001) and third- or further-line chemotherapy (15 months versus 6 months, p&lt; 0.001) had significantly longer median OS. The presence of extracranial extrathoracic metastasis, number of brain metastasis, and Tx modality for brain metastasis showed no significant association with OS. In multivariate analysis, third- or further-line chemotherapy (24 pts) was the only independent prognostic factor for favorable OS ( p&lt; 0.001). Pts who underwent third- or further-line chemotherapy were characterized by high proportion of non-squamous histology ( p= 0.016), extracranial extrathoracic metastasis ( p= 0.015), and TKI Tx ( p&lt; 0.001). Conclusions: The present study suggests that judicious but active use of chemotherapy after appropriate Tx for brain metastasis may result in favorable outcome in NSCLC pts with synchronous brain metastasis, regardless of the number of brain metastatic lesions or local Tx modalities.

Association between time to first subsequent therapy (TFST) and overall survival (OS) in previously untreated patients with ovarian cancer (OC): A SEER Medicare database analysis.

e17095 Background: TFST may be a patient-relevant indicator of efficacy beyond progression in OC, however, the association between TFST and OS is unknown. We analyzed the SEER Medicare database to determine whether OS varied by TFST in previously untreated patients with OC. Methods: From the SEER-Medicare linked database, we identified newly diagnosed OC patients (≥66 years) who initiated first-line chemotherapy between 2009 and 2015. Patients were followed through the end of 2016. TFST was defined as the time from initiation of first-line chemotherapy until the start of subsequent therapy or death. Cox models summarized the overall association between TFST and OS through hazard ratios (HRs), and by TFST strata for patients who had a TFST event. In case hazards were non-proportional, we examined the fit of independent parametric survival curves. Results: In the cohort of 1407 patients, 1005 patients had a TFST event. Median age was 74 years and 34.9% were alive at the time of this analysis. For population with a TFST, the median TFST was 13.1 months and median OS was 30.88 months (HR = 0.29, 95% CI: 0.26, 0.32). Among patients &lt; 75 years, the median TFST was 13.65 months and the median OS was 37.07 months (HR = 0.24, 95% CI: 0.21, 0.28). In the full cohort of 1407 patients, the best-fitting distributions accelerated failure time models under which the (unrestricted) mean TFST and OS were 44.9 and 73.8 months respectively. This indicated that on average TFST was an acceleration of OS by a factor of 39%. Conclusions: In this elderly population of previously untreated OC, longer TFST was associated with longer OS. Limitations of this analysis include censoring of OS and immortal time bias. [Table: see text]