Difference In Median Overall Survival Research Articles

PD-L1 tumor proportion score and clinical benefit from first-line pembrolizumab in patients with advanced nonsquamous versus squamous non-small cell lung cancer (NSCLC).

9539 Background: The predictive value of PD-L1 tumor proportion score (TPS) on NSCLC tumor cells as a biomarker for response to PD-(L)1 inhibitors is well established. However, its histology specific value in advanced (a) squamous (Sq) versus nonsquamous (NS) cancers remains unclear. Here, we used real world data to assess the differential value of PD-L1 TPS as a predictive biomarker for overall survival (OS) after first-line pembrolizumab (P) in patients (pts) with Sq versus NS NSCLC. Methods: Inclusion criteria for this analysis of the Flatiron Health EHR-derived de-identified database required that pts were diagnosed with aNSCLC, tested for PD-L1 TPS and received a numerical result, had no alteration in EGFR, ALK, or ROS, and received first-line, single agent P. The primary endpoint was overall survival (OS) from the first dose of P in patients with TPS ≥ 50% (H) compared to patients with TPS < 50% (L). Due to the violation of the proportional hazards assumption, a generalized gamma model of OS was used, adjusting for demographic variables and estimated median OS and their confidence intervals with the bootstrap method. The PD-L1-histology interaction was examined by comparing the differences in median OS (H vs. L) between Sq and NS patients. Results: Of 1560 pts with NSCLC treated from 1/2011 – 5/2019, 1055 had NS and 405 Sq. No meaningful differences in age, gender, or smoking history were seen between PD-L1 H and L pts with either histology. Among NS pts, H had significantly longer OS than L, with unadjusted hazard ratio (HR) of 0.71 (95% CI: 0.53 - 0.94; p = 0.018). Among Sq pts, H was not associated with longer OS than L, with unadjusted HR 0.89 (95% CI: 0.64 - 1.25; p = 0.514). Based on the generalized gamma model, PD-L1 H in Sq patients was associated with a 0.19 year improvement in median OS (95% CI: -0.22-0.49, P = 0.283), whereas PD-L1 H in the NS group was associated with a 0.70 year improvement in OS (95% CI: 0.34-1.05, P < 0.001). The median improvements between the Sq and NS patients were significantly different (P = 0.034), after adjusting for demographic variables. Conclusions: PD-L1 TPS of ≥ 50% predicted longer OS in pts with NS NSCLC treated with first-line P compared to pts whose tumors had a TPS of < 50%. However, no relationship between PD-L1 TPS and OS after first-line P was seen in patients with Sq NSCLC. These data suggest that PD-L1 may not be an appropriate predictive biomarker for checkpoint inhibitor use in NSCLC with squamous histology.

Assessment of FcgRIIIA single nucleotide polymorphisms (SNPs) on the efficacy of IgG1 monoclonal antibodies (mAbs) in PANGEA study patients (pts) with advanced gastroesophageal adenocarcinoma (aGEA).

4526 Background: Targeted therapies (Ttx) have had limited efficacy in aGEA. The phase IIa PANGEA trial assessed the outcomes of pts treated with IgG1 mAbs targeting receptor tyrosine kinases (RTKs) or PD-1 based on predefined molecular groups. The fragment C (Fc) portion of mAbs binds to IgG receptors (FcgR) of immunologic effector cells such as natural killer (NK) cells, leading to antibody-dependent cell-mediated cytotoxicity (ADCC). The FcgR subclass, FcgRIIIA, has genetic variants with different Fc binding affinities. A single nucleotide polymorphism (SNP) in FcgRIIIA substitutes phenylalanine (F) with valine (V) at amino acid position 158, enhancing FcgR’s affinity for the IgG1 Fc domain. Pts with V/V or V/F FcgRIIIA allotypes have enhanced NK cell binding affinity compared to the homozygous F/F allotype. We evaluated the association of FcgRIIIA SNPs on Ttx outcomes amongst PANGEA pts and another cohort of aGEA pts treated with IgG1 mAbs. Methods: Whole-blood samples were identified from aGEA pts (N = 104), including 70/80 available PANGEA pts, who were treated with an IgG1 mAb (trastuzumab 24, anti-EGFR 21, anti-PD1 30, ramucirumab 48) in at least 1 Ttx line. After lymphocyte DNA extraction, FcgRIIIA genotyping was performed. The Cox proportional hazard model and log-rank tests, adjusted for pt age, were used to assess for an association of genotype with overall survival (OS). Results: Of 104 genotyped pts, the F/F, F/V & V/V genotypes were observed at a frequency of 32%, 51% and 17% respectively. There was no significant difference in median OS (mOS) between the F/F, F/V or V/V or comparing F/F vs V/F+V/V overall, nor in the PANGEA-only cohort. A trend of increased mOS was seen in 20 non-PANGEA pts harboring F/V or V/V compared to 14 F/F pts (mOS 43.4 vs 23.1 months, HR 0.41 [0.15-1.14] p = 0.09). However, 3-year OS rates trended higher in V/F+V/V pts (22%, 16/71) compared to F/F pts (7%, 2/33) (p = 0.09). At 3 years, 50% of V/V+V/F non-PANGEA pts were alive versus 13% of F/F pts (p = 0.04), while 13% of V/V+V/F PANGEA pts were alive versus 0% of F/F pts (p = 0.32). Conclusions: Amongst pts receiving IgG1 mAbs, the high affinity V FcgRIIIA SNP enriched for a subgroup of ‘extreme responders’ alive 3 years from diagnosis. Multivariate analyses accounting for baseline characteristics in a larger number of pts are ongoing to further elucidate the role of FcgRIIIA SNPs as predictive biomarkers. These findings may have implications on IgG1 mAb ADCC optimization.

Survival analysis of CLL/SLL patients with Richter’s transformation to DLBCL: An analysis of the SEER database.

e20024 Background: Richter's transformation (RT) from Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL) to a Diffuse Large B-Cell Lymphoma (DLBCL) is a rare complication with an estimated incidence of less than 5% and a poor prognosis based on small retrospective studies. Large studies investigating the natural history and patient outcomes with this entity of DLBCL are lacking, and prospective data on the best treatment option are scarce and limited by rarity of this condition. Methods: We queried the US Surveillance, Epidemiology, and End Results (SEER) 18 database for patients sequentially diagnosed with CLL/SLL followed by DLBCL from January 2000 to December 2016 with a cutoff latency of 2 months. Data obtained included patient demographics, history of treatment for CLL/SLL, overall survival (OS) after DLBCL diagnosis and latency period between CLL/SLL and DLBCL diagnoses. For comparison, SEER data was obtained for patients with de novo DLBCL and for CLL/SLL patients without RT in the same date range. Survival was estimated by Kaplan Meier method and log rank test was used to compare outcomes. Results: 471 patients who developed RT to DLBCL and 98425 patients with de novo DLBCL were identified. The median time for developing RT to DLBCL was 54 months. Median OS was worse for DLBCL arising from RT compared to de novo DLBCL (64 months versus 10 months, p < 0.0001). In patients with RT to DLBCL, no statistically significant difference in median OS was seen in patients who received treatment for CLL/SLL versus those assigned as No/Unknown treatment status (p = 0.51). In patients with CLL/SLL in the specified time period; median OS was significantly lower for those who developed RT to DLBCL compared to those who did not (91 months versus 100 months, p = 0.0012). Conclusions: DLBCL arising from RT in CLL/SLL patients is not necessarily a late complication. Prognosis is dismal with a trend towards a poor OS in the subset of patients with pretreated CLL/SLL. This large population study correlates with prior reports and highlights the need for prospective data to inform prognosis and treatment decisions.

A multi-institution analysis of molecular biomarkers in patients with metastatic colorectal cancer in ethnically diverse populations.

e16074 Background: Differences in clinical outcomes for metastatic CRC (mCRC) have been reported across racial-ethnic groups, particularly between Hispanics (HA), non-Hispanic Blacks (NHB), and non-Hispanic Whites (NHW), with limited information available among Asian Americans (AA). We examined if there were differences in clinical outcomes by molecular drivers between these groups in a pooled analysis of two institutions serving ethnically diverse patient populations. Methods: We retrospectively examined 1927 mCRC patients from Montefiore Medical Center and the University of Texas MD Anderson Cancer Center. Mutations in KRAS, NRAS, and BRAF were determined by polymerase chain reaction or next generation sequencing. Mutations were then correlated with overall survival (OS). Results: Our patient population consisted of 1153 (61%) NHW, 314 (17%) HA, 320 (17%) NHB and 59 (3.1%) AA. Across subgroups, borderline significant difference in prevalence of BRAF mutation was observed (p = 0.04), with higher prevalence observed among NHW as compared to other groups. No differences were observed for KRAS and NRAS mutation prevalence. In univariate analysis, the median survival for BRAF MT tumors was 18.5 months vs 32 months for BRAF WT tumors (p < 0.0001). Similarly, median OS for KRAS WT, KRAS MT, NRAS WT and NRAS MT was 29.3, 27.4, 31 and 31.5 months respectively, with no differences between groups. In subgroup analysis by race/ethnicity, median OS in BRAF MT NHW was 19.98 months vs 33.48 in BRAF WT NHW (p < 0.0001). Similar trends were observed in HA and NHB. No differences in median OS were observed by KRAS or NRAS mutation status across racial-ethnic groups. Conclusions: This multi-institution study found no meaningful difference in the prevalence of molecular drivers across racial-ethnic groups. Additionally, in our subgroup analyses, OS based on the presence of a specific molecular driver mutation did not seem to vary by race. For example, RAS mutated and BRAF mutated patients showed similar OS across racial-ethnic groups. Our study demonstrates that reported differences in clinical outcomes by race and ethnicity in the literature are unlikely to be dependent on the difference in the presence of certain molecular drivers.

Consensus molecular subtypes (CMS) as a marker for treatment and disease biology in metastatic colorectal cancer (CRC).

4089 Background: Consensus molecular subtypes (CMS) categorize colorectal cancer (CRC) into groups based on gene transcription and are prognostic in early-stage and first-line metastatic settings. Their impact on treatment history is unknown. We hypothesized that the best prognosis CMS2 would have higher utilization of liver-directed therapies and maintenance chemotherapy over the worst prognosis CMS4. Methods: Primary surgical resection specimens were annotated for CMS on a translational protocol in a 5FU-refractory metastatic CRC population. Specimens that had neoadjuvant chemotherapy or radiation were excluded. CMS1, CMS3 and indeterminate CMS were also excluded. Liver-directed therapies were defined as any surgery, direct injection of cytotoxics or microspheres, radiation or radiofrequency ablation. Multiple occurrences of liver-directed therapies or maintenance chemotherapy in the same patient were recorded once for statistical tests of association. Results: CMS1 (7.4%), CMS3 (8.2%) and indeterminate calls (4.1%) accounted for 20% of all samples tested. There were 43 (44%) CMS2 and 55 (56%) CMS4 patients eligible. Age, stage at diagnosis, mismatch repair and RAS mutational status were similar in both groups. Left-sided tumors were more common in CMS2 (79%) than CMS4 (42%), p = .001. The median overall survival (OS) from stage IV diagnosis was 40 [34 - 51] versus (vs) 28 [21 – 33] months (p < .0001) for CMS2 vs CMS4 respectively. Liver-directed therapy was greater in CMS2 (53%) vs CMS4 (31%), p = .024. The number further increased when multiple treatments in a single patient were taken into account. Microsphere injection, radiation and liver surgery combined with RFA were the most skewed towards CMS2 over CMS4. No difference in median OS was seen from first liver-directed therapy in CMS2 vs CMS4 (29 vs 27 months, p = .31). There was a trend towards greater maintenance chemotherapy in CMS2 (47%) vs CMS4 (29%), p = .076. Conclusions: Better prognosis with CMS2 is consistent with other studies. Significantly increased liver-directed therapy was observed in CMS2. Selection criteria for liver-directed therapy such as slowly progressing, oligometastatic and hepatic-confined disease may be enriching for CMS2 and gives insight into the natural history of this subtype.

Impact of empirically eliminating 5-fluorouracil (5-FU) bolus and leucovorin (LV) in patients with metastatic colorectal cancer (mCRC) receiving first-line treatment with mFOLFOX6.

4022 Background: Systemic chemotherapy with a 5-FU-based regimen, such as mFOLFOX6, is the preferred first line treatment option for mCRC. Due to hematologic toxicities associated with the 5-FU bolus component, providers may choose to eliminate it empirically in patients receiving palliative therapy. This study aimed to assess the impact of empirically eliminating the 5-FU bolus and LV from first line treatment with mFOLFOX6 in mCRC. Methods: This was a retrospective chart review of patients ≥ 18 years old with mCRC receiving palliative first line mFOLFOX6 chemotherapy with (bolus) or without (non-bolus) the 5-FU bolus and LV components from January 1, 2015 through August 31, 2019 at Moffitt Cancer Center. The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival (OS), disease control rate (DCR) defined as partial response and stable disease at first scan, utilization of growth factor support and safety. Results: Data analysis cutoff was December 31, 2019, with 61 patients included in the bolus arm and 72 in the non-bolus arm. Median follow-up time was 21.8 months. No difference was found in median PFS (8.12 vs. 6.64 months, p=0.787) or OS (29.36 vs. 21.6 months, p=0.395) between the bolus and non-bolus arms, respectively. Observed DCR at first scan was similar between both arms (47.3% vs. 52.7%, p=0.44). Utilization of growth factor support was significantly higher in the bolus arm (73.7% vs. 26.3%, p=0.012). Fewer grade ≥ 3 treatment-related hematologic adverse events (AE) were seen in the non-bolus arm (37.7% vs. 22.2%, p=0.058) (table). Conclusions: This is the only study to date that analyzed the impact of empirically eliminating 5-FU bolus and LV from first line palliative therapy with mFOLFOX6 in mCRC. Results showed no significant difference in median PFS or OS. Despite reduced growth factor utilization, the non-bolus arm demonstrated a favorable safety profile with less treatment-related hematologic grade ≥ 3 AE. The results of this study warrant consideration of empirically eliminating 5-FU bolus and LV from the mFOLFOX6 regimen to avoid additive toxicities without negatively impacting efficacy. [Table: see text]

Immune checkpoint inhibitors’ (ICI) efficacy according to PD-L1 expression for advanced or metastatic NSCLC: Systematic review and meta-analysis.

e21723 Background: Blocking PD-1 pathway has become a milestone in treating many tumors, including non-small cell lung cancer (NSCLC) for first and second line therapies. Although their benefits for some patients, these drugs are not full available in developing countries due to high treatment cost. In this study, we assessed the efficacy of five PD-1 or PD-L1 blockers (nivolumab, pembrolizumab, atezolizumab, durvalumab and avelumab), associated or not to chemotherapy, according to PD-L1 expression. Methods: We performed a systematic review and meta-analysis of randomized clinical trials in the databases MEDLINE/Pubmed, EMBASE, COCHRANE Library and LILACS up to November 2018. We selected trials comparing ICI alone, or associated with ICI or chemotherapy, versus chemotherapy or placebo. Primary outcome was overall survival (OS) and secondary outcome was progression free survival (PFS). Risk of bias of included trials was assessed by Cochrane’s recommended tool and data meta-analysis was performed by Review Manager V5.3 software. Results: We assessed OS and PFS of 12 trials in our meta-analysis. The methodological quality was considered moderate according to Cochrane’s tool. The pooled hazard ratio were 0.70 (95% CI 0.63, 0.78; p < 0.01; I² = 58%) for OS and 0.75 (95% CI 0.64, 0.89; p < 0.01; I² = 88%) for PFS. Subgroup analysis for PD-L1 < 1%, ≥ 1% and ≥ 50% showed OS of 0.78 (95% CI 0.64, 0.95; p = 0.09; I² = 46%), 0.69 (95% CI 0.59, 0.81; p < 0.01; I² = 79%) and 0.57 (95% CI 0.48, 0.68; p = 0.10; I² = 40%), respectively. Data for PFS were 0.85 (95% CI 0.71, 1.03; p = 0.21; I² = 31%), 0.77 (95% CI 0.64, 0.92; p < 0.01; I² = 83%) and 0.53 (95% CI 0.46, 0.62; p = 0.14; I² = 36%), respectively. Conclusions: Our data suggest a dose-response relationship between PD-L1 level and survival outcomes. It was not possible to conduct our meta-analysis by median OS and median PFS difference once these data were not available for every trial we selected. Considering the high price of immune therapy and budget limitations in developing countries’ health system, our findings could optimize health technology assessment agencies recommendations for treating NSCLC with high expression of PD-L1.

Immortal time bias in the association between toxicity and response for immune checkpoint inhibitors: A systematic review and meta-analysis.

e15080 Background: A number of studies have addressed the association between Immune related Adverse Events (IrAE) and outcome in patients treated with Immune Checkpoint Inhibitors (ICI). Only a minority of them considered the effect of immortal time bias (ITB), and results of these papers are conflicting. The aim of our meta-analysis was to assess the relationship between IrAE and outcomes for patients treated with ICIs, with a focus on ITB in weighing the role of this association. Methods: PubMed, Embase (Ovid), and Scopus were searched through January 2, 2020. Studies reporting the prognostic impact of IrAE development on outcome in advanced cancer patients treated with anti PD-1 or PD-L1.Two investigators independently extracted data from each study following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses) guideline. Author name, cancer type, PD-1 and PD-L1 inhibitor used, number of patients, number and type of all adverse events, presence of a landmark analysis, median OS and PFS and difference between patient with or without IrAE in terms of OS and PFS (Hazard Ratio) and ORR (Odds Ratio) were extracted. Data were pooled using a random-effects model. Main outcome were Overall Survival (OS), Progression Free Survival (PFS) and Overall Response Rate (ORR). Analysis was performed with dedicated software (R studio version 1.2.1335, metafor package). Results: A total of 29 articles comprising 7430 patients were included. 7 papers published the results of survival analysis according to landmark analysis, 2 papers published only the naïve analysis while stating that a landmark analysis resulted non significant, and the others did not perform a landmark analysis. IrAEs were associated with improved outcomes with high heterogeneity ( I2 70.8%, p < 0.001 for OS; 65.7%, p 0.002 for PFS; 62.1%, p 0.001 for ORR). When subgroup analysis was performed according to the adoption of a landmark approach, the association between IrAE and outcome remains significant for OS, PFS and ORR but the effect size was smaller ( HR 0.61 vs 0.41 for OS, ANOVA Q-test for difference between subgroup p = 0.015; HR 0.66 vs 0.47 for PFS, ANOVA Q-test p 0.029; OR 2.59 vs 6.77 for ORR, ANOVA Q-test p < 0.001) while heterogeneity was substantially reduced (I2 for papers using LM 43% for OS, p 0.115; 9.7% for PFS, p 0.355; 0.0% for ORR, p 0.556). Conclusions: Our analysis suggests a significant confounding effect of ITB as well as a real effect of IrAE development on outcome.

Efficacy and safety of nivolumab for renal cell carcinoma in patients over 75years old from multiple Japanese institutes.

Despite nivolumab being increasingly used for treating metastatic renal cell carcinoma (mRCC), differing findings have been reported about its efficacy and safety in elderly patients. Thus, this study was aimed at evaluating nivolumab's efficacy and safety for treating mRCC in Japanese patients aged ≥ 75years. From March 2013 to August 2019, 118 mRCC patients (89 men and 29 women) were treated with nivolumab. The objective response rates (ORRs) were compared between patients aged ≥ 75 and < 75years. Progression-free survival (PFS), overall survival (OS), and adverse events (AEs) were also compared between the two age-groups. The median follow-up duration after nivolumab initiation was 10months. At the time of nivolumab initiation, 22 and 96 patients were aged ≥ 75 and < 75years, respectively. Intergroup differences in patient characteristics except for age were not significant. Furthermore, intergroup differences in ORR (14 vs 23%; P = 0.367), PFS (HR 0.74, 95% CI 0.37-1.51; P = 0.414), and median OS (HR 1.29, 95% CI 0.68-2.46; P = 0.433) were not significant. The incidence of nivolumab discontinuation due to AEs was significantly higher in the ≥ 75years group (27% vs 7%; P = 0.028), although the intergroup difference in the AE incidence rate was not significant (55% vs 43.8%; P = 0.535). Nivolumab's effectiveness was comparable between the two patient groups, except for early AE-related discontinuation in the ≥ 75year group.

Comparison of induction strategies and responses for acute myeloid leukemia patients after resistance to hypomethylating agents for antecedent myeloid malignancy

Outcomes in patients with secondary acute myeloid leukemia (sAML) (including therapy related myeloid neoplasms and AML with myelodysplasia related changes (MRC)) are poor. Patients treated with hypomethylating agents (HMAs) for antecedent hematological malignancy (AHM) have suboptimal responses to induction chemotherapy upon transformation to AML. We investigated outcomes after various induction strategies in patients with sAML who had prior HMA exposure. We identified 242 patients with sAML who had prior HMA treatment for AHM and later received induction chemotherapy upon AML transformation and divided into 3 cohorts based on induction regimen: (A) CLAG/M (B) 7 + 3 and (C) CPX-351. The CR/CRi rate was 53% in cohort A, 32% in cohort B and 41.2% in cohort C (p = 0.005 between cohort A and B) (p = 0.329 between cohorts A and C) (p = 0.402 between cohorts B and C). The early death rates were not significantly different among the three cohorts (p = 0.200). In patients who received ≤4 cycles of HMAs prior to AML transformation, response rates to CPX-351 were higher (64.3%) with a trend toward better overall survival (OS) (19.9 vs. 5.5 months) compared to >4 cycles (p = 0.092). There was no significant difference in median OS among the 3 groups: cohort A (7.27 months), cohort B (7.63 months) and cohort C (7.07 months) (p = 0.887). We demonstrate that CLAG/M and CPX-351 yield higher CR/CRi rates compared to 7 + 3 in patients with sAML after HMA failure. Median OS remains poor and did not differ among the 3 groups, illustrating the unmet need for more efficacious therapy for sAML patients following HMA failure.

Real-world prognostic factors in autotransplanted multiple myeloma patients with severe renal impairment: study of the Polish Myeloma Study Group

IntroductionThe prognostic factors in autotransplanted multiple myeloma (MM) patients with concomitant advanced chronic kidney disease (CKD) are poorly understood, limited, and controversial.Material and methodsWe retrospectively analysed 44 patients with MM and CKD (eGFR &lt; 40 ml/min), present both at diagnosis and at autologous stem cell transplantation (ASCT), with no improvement of renal function in-between.ResultsPatients exhibiting deeper paraprotein responses to pre-transplant treatment predicted better response post ASCT (odds ratio (OR) = 11.6, p = 0.028) and longer progression-free survival (PFS) (hazard ratio (HR) = 0.23, p = 0.017). Higher albumin concentration (per increase of 1 g/dl) (HR = 0.41, p = 0.03) and melphalan 140 mg/m2 versus higher melphalan doses (HR = 0.86, p = 0.008) were associated with longer PFS. Performance status (ECOG 0-1 versus ≥ 2) (HR = 0.28, p = 0.0036), higher albumin concentration (HR = 0.43, p &lt; 0.037), and melphalan 140 mg/m2 versus higher melphalan doses (HR = 0.48, p = 0.081) decreased the risk of death. Three of 32 dialysis-dependent patients became dialysis independent (DID), and 5 of 12 in the DID group had eGFR improvement post ASCT. The median PFS was 2.3 years, which was shorter for DID compared to DD patients (0.7 vs. 3.3 years, respectively). The median overall survival (OS) was 3.6 years, there was no difference in median OS between the groups (4.0 vs. 3.5 years, respectively).ConclusionsOptimal patient selection including good performance status and higher albumin concentration (with every increase of 1 g/dl), chemotherapy-responsive disease pre-ASCT, melphalan dose adjusted to CKD, and intensive post-transplant supportive care are crucial to achieve acceptable results of treatment of MM patients with CKD.

Combined conventional transarterial chemoembolization with Mitomycin and percutaneous ablation for unresectable hepatocellular carcinoma.

Conventional transarterial chemoembolization (cTACE) has been the standard treatment for intermediate stage hepatocellular carcinoma (HCC). For early stage HCC, percutaneous ablation is a curative option. There is growing evidence to support combined therapy to improve tumor response and overall survival (OS) in patients with unresectable HCC. The goal of this study is to retrospectively review a single institution patient population who underwent the combined approach to determine its efficacy and safety, and possible predictive factors for OS and tumor response. Retrospective analysis identified all patients that underwent c-TACE with Mitomycin followed by percutaneous ablation from 2011 to 2016 at our institution. Efficacy was assessed by OS, time to progression (TTP), and tumor response according to mRECIST criteria. Initial imaging was obtained 1 month after each treatment and after complete response was achieved, every 3 months for 2 years. Percentage of Lipiodol uptake was determined at 30-day follow-up with contrasted abdominal CT. Safety was assessed using Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Multiple linear regressions were conducted to predict OS and number of progression-free survival days based on potential predictive factors. A total of 50 patients were identified. At 1-month follow-up, objective response (CR + PR) was achieved in 44 patients (88%). The median OS was 26.6 months and median TTP was 9.7 months (n=50). There was no statistically significant difference in median OS between patients with different lesion size (P=0.95), BCLC stage (P=0.84) or Lipiodol uptake (P=0.36). Higher albumin/bilirubin ratio was significantly correlated with improved OS (P=0.024). Combined c-TACE and PTA is a safe and effective approach for patients with unresectable HCC. Elevated albumin/bilirubin ratio was a predictor for improved OS.

Does presence of bone metastases portend worsened prognosis in metastatic renal cell carcinoma? Analysis of the REMARCC (Registry of MetAstatic RCC) database.

655 Background: The presence of brain metastases and bone metastases are generally understood to herald worsened prognosis following nephrectomy in patients with renal cell carcinoma (RCC). However, we sought to determine the effect of bone metastases on outcomes when already present at the time of cytoreductive radical nephrectomy (RN). Methods: Multicenter retrospective analysis of mRCC patients from the REgistry of MetAstatic RCC) REMARCC. Demographics, clinical variables, and outcomes were collected. Patients were stratified into low, medium, and high-risk groups based on Motzer Criteria, and analysis of impact of bone metastases was conducted within each group utilizing Kaplan-Meier analysis (KMA). Multivariable analysis (MVA) was utilized to identify predictors for outcomes. Primary outcome was progression-free survival (PFS) and secondary outcome was overall survival (OS). Results: A total of 447 patients (low- n=30, intermediate- n=208, and high-risk mRCC n=123, median follow-up 14.3 months) were included in the analysis. 124 patients had bone metastases and 323 had mRCC but no bone metastases. No significant demographic differences were noted between groups. KMA (Figure) showed no difference in median PFS for bone metastases vs. non bone metastases groups (6.1 vs. 6.4 months, p=0.973). KMA showed no difference in median OS (25.5 vs. 26.5 months, p=0.958). Similarly, stratification of patients into different Motzer risk categories did not demonstrate difference between bone vs. none bone mRCC for PFS and OS. MVA for PFS demonstrated increasing Motzer risk category (low risk referent vs. intermediate OR 1.89, p=0.006, high risk OR 3.24, p&lt;0.001) as independent predictors. MVA for OS revealed increasing Motzer risk category (low ref, vs. intermediate OR 1.88, p=0.033, high risk 5.17, p&lt;0.001) as being predictive. In neither analysis was presence of bone metastases significant (PFS p=0.690, OS p=0.268). Conclusions: Presence of bone metastases does not independently predict survival or oncologic outcomes in mRCC. While further validation is needed, the prognostic significance of bone metastases may be less than previously thought.

Impact of palliative care in patients with metastatic esophageal cancer declining chemotherapy.

315 Background: Palliative care has been associated with improved overall survival (OS), but limited data exist in metastatic esophageal cancer (mEC). We investigated the impact of palliative care in patients with mEC who declined chemotherapy (CTX). Methods: The National Cancer Database was used to identify patients between 2004-2015. Patients with M1 disease who declined CTX and had known palliative care status (surgery, radiotherapy [RT], pain management, or any combination of) were included. Cases with unknown CTX, RT, or nonprimary surgery status were excluded. Kaplan-Meier estimates of OS were calculated. Univariable and multivariable Cox regressions were performed. Results: Among 140,234 EC cases, we identified 1,493 patients who declined CTX and had complete data. Median age was 70 years, most (66.3%) had a Charlson Comorbidity Index (CCI) of 0, and 37.1% were treated at an academic center. Most (72.7%) did not receive palliative care. Median OS was 2.53 months (mos), with no statistically significant difference in median OS between those receiving palliative care (2.83 mos, 95% confidence interval [CI] 2.53-3.12) vs. no palliative care (2.37 mos, 2.2-2.56; p = 0.288). On univariable analysis, treatment at an academic center (hazard ratio [HR] 0.90, 0.80-1.00) and CCI ≥2 (HR 1.20, 1.00-1.42) were predictive of OS (p &lt; 0.05). On multivariable analysis, male sex (HR 1.23, 1.08-1.40), South geographic region (HR 1.23, 1.04-1.46), CCI of 1 (HR 1.17, 1.03-1.32), higher grade (HR 1.21, 1.07-1.38), and higher T stage (HR 1.39, 1.12-1.73) were associated with poor OS (p &lt; 0.05). Conclusions: Palliative care conferred a numerically higher, but not statistically significant difference in OS among patients with mEC declining CTX. Quality of life metrics, inpatient status, and subgroup analyses are important for examining the role of palliative care in mEC and future studies are warranted.

A randomized phase III trial comparing primary tumor resection plus chemotherapy with chemotherapy alone in incurable stage IV colorectal cancer: JCOG1007 study (iPACS).

7 Background: It is still controversial whether primary tumor resection (PTR) before chemotherapy (CTX) improves overall survival (OS) of colorectal cancer (CRC) patients (pts) with synchronous unresectable metastases. There are several retrospective analyses suggesting better outcomes in pts who underwent PTR compared to pts without it, but no prospective studies confirming these results. We conducted a randomized controlled trial to confirm the superiority of PTR plus CTX to CTX alone in asymptomatic unresectable stage IV CRC patients. Methods: Eligibility criteria included histologically proven colon and upper rectal adenocarcinoma, cT1-4 without involvement of other organs, presence of three or less unresectable factors confined to either liver, lungs, distant lymph nodes, or peritoneum, aged 20-74, no symptoms due to primary tumor and PS 0-1. Eligible patients were randomized to either PTR followed by CTX or CTX alone. CTX regimens were declared before study entry; options included mFOLFOX6 plus bevacizumab or CapeOX plus bevacizumab. The primary endpoint was the OS. The planned sample size was 140 pts per arm, with one-sided alpha of 5%, and 70% power detecting a median OS difference of 8 months (24 months vs. 32 months). Results: Between Jun 2012 and Apr 2019, 160 patients were randomized. 78 pts were allocated to PTR plus CTX, and 82 pts to CTX alone. When the first interim analysis was performed in Sep 2019, with 50% (114/227) of the expected events observed, the DSMC recommended the early termination of the trial based on its futility. With a median follow-up period of 22.0 months for 160 patients, median OS was25.9 months (95% CI 19.9 – 31.5) with PTR plus CTX and 26.7(21.9 – 32.5) with CTX alone (hazard ratio 1.10 [0.76 – 1.59], one-sided p = 0.69). Median PFS was 10.4 (8.6-13.4) with PTR plus CTX and 12.1 (9.4 – 13.2) with CTX alone (hazard ratio 1.08 [0.77 – 1.50]). There were three treatment related deaths following PTR due to postoperative complications. Conclusions: PTR followed by CTX has no survival benefit over CTX alone. PTR is not recommended for CRC patients with asymptomatic primary tumor and synchronous unresectable metastases. Clinical trial information: UMIN000008147.

Resection of isolated distant nodal metastasis in metastatic colorectal cancer

BackgroundLittle is known regarding the role of resection in patients with colorectal cancer (CRC) who present with isolated non-regional lymph node metastasis (NRLNM). MethodsUsing the Surveillance, Epidemiology and End Results database, we identified patients diagnosed with CRC and NRLNM from 2004 to 2013. ResultsA total of 849 patients presented with CRC and isolated NRLNM. Of these, 90 (10.6%) underwent resection of NRLNM. Median overall survival (OS) did not differ for patients who underwent resection of NRLNM compared to those who did not (33 versus 29 months, p = 0.68). Subgroup analysis by primary tumor site, also did not demonstrate a difference in median OS. Cox proportional hazard model revealed older age (Hazard ratio [HR] 1.34, 95% Confidence Interval [CI] 1.17–1.53, p < 0.0001), higher tumor grade (HR 1.81, 95% CI 1.52–2.16, p < 0.0001), and earlier year of diagnosis (HR 1.34, 95% CI 1.17–1.53, p < 0.0001) were associated with decreased OS. There was no survival difference between those who underwent resection of NRLNM compared to those who had not (HR 0.997, p = 0.28). ConclusionResection of NRLNM in patients with CRC is not associated with an OS benefit. Further studies are needed to determine if there is a subset of patients who could potentially benefit from this resection strategy.

Longitudinal model-based meta-analysis for survival probabilities in patients with castration-resistant prostate cancer.

The aims of this longitudinal model-based meta-analysis (MBMA) were to indirectly compare the time courses of survival probabilities and to identify corresponding potential significant covariates across approved drugs in patients with castration-resistant prostate cancer (CRPC). A systematic literature review for monotherapy studies in patients with CRPC was conducted up to August 8, 2018. The time courses of progression-free survival (PFS) and overall survival (OS) were fitted with parametric survival models. Covariate analyses were performed to determine the impact of treatment drugs, dosing regimens, and patient characteristics on the survival probabilities. Simulations were carried out to quantify the magnitude of covariate effects. A total of 146 studies including clinical trials and real-world data on longitudinal survival probabilities in 20,712 patients with CRPC were included in our meta-database. The time courses of PFS and OS probabilities were best described by the log-logistic model. There was no significant difference in median OS and PFS between docetaxel, cabazitaxel, abiraterone acetate, and enzalutamide. There was no significant dose-response relationship in PFS or OS for docetaxel at 50 to 120mg/m2 every 3weeks (Q3W) and cabazitaxel at 20 to 25mg/m2 Q3W. Model-based simulations indicated that PFS probability was associated with chemotherapy, Gleason score, and baseline prostate-specific antigen (BLPSA), while OS probability was associated with chemotherapy, Gleason score, visceral metastasis, Eastern Cooperative Oncology Group performance status, and BLPSA. Our modeling and simulation framework can be applied to support indirect comparison, dose selection, and go/no-go decision-making for new agents targeting CRPC.

Assessment of Systemic Inflammatory Response and Nutritional Markers in Patients With Trastuzumab-treated Unresectable Advanced Gastric Cancer

To determine whether markers of systemic inflammatory response and nutrition are a predictor of treatment response in patients with trastuzumab-treated unresectable advanced gastric cancer. Twenty-one patients who received chemotherapy for unresectable advanced gastric cancer at Kochi Medical School from 2013 to 2020 were enrolled. Clinicopathological information and systemic inflammatory response data were obtained retrospectively to investigate associations between baseline cancer-related prognostic variables and survival outcomes. The median overall survival (OS) and progression-free survival (PFS) for the whole cohort were 24.5 (range=1.9-88.4) months and 7.0 (range=2.0-23.4) months, respectively. The objective response rate and disease control rate were 52.4% and 81.0%, respectively. The median PFS for patients with a neutrophil to lymphocyte ratio (NLR) <2.8 was significantly longer than that for those with NLR ≥2.8 (8.9 vs. 6.0 months; p=0.048). Although the median OS also tended to be longer for patients with NLR <2.8, the difference was not statistically significant. No significant differences in median OS and PFS were observed between patients with a prognostic nutrition index (PNI) <41.6 and those with PNI ≥41.6. An NLR ≥2.8 is a predictor of poorer prognosis in patients receiving systemic treatment with trastuzumab and chemotherapy for unresectable advanced or recurrent gastric cancer.

Malignified IPMN and PDAC have comparable overall survival: A western single center cohort study

Background: Outcome after resection for Pancreatic Ductal Adenocarcinoma (PDAC) is well known. Prognosis after resection for malignified IPMN (mal-IPMN), however, is not well studied and present data is inconsistent. The aim of this study was to compare outcomes after resected PDAC and mal-IPMN in a large western single-center cohort. Material and Methods: This was a retrospective observational cohort study comparing clinical and pathological findings as well as disease-free survival (DFS) and overall survival (OS) of patients resected for mal-IPMN and PDAC at Karolinska University Hospital between 2011-2017. Clinicopathological findings were analyzed by univariate (Mann-Whitney U, Pearson Chi-square or Fishers test), bivariate (Kaplan-Meier method and Log-Rank test) and multivariate analyses (Cox Regression). Results: In total 322 patients were included, 247 with PDAC and 75 with mal-IPMN. Univariate analysis showed that patients with mal-IPMN compared to PDAC had less often pre-operative symptoms (75 vs 88%, p=0.004), lower CA19.9 levels (66 vs 125 U/mL, p=0.009), less recurrence rate (40 vs 68%, p<0.001) and the median DFS was longer (11.6 vs 10.8 months, p=0.03). The mal-IPMN tumors were less often localized in the head (68 vs 81%, p <0.001), they were less often graded as low/undifferentiated (60 vs 73%, p=0.034) and they did not invade lymph nodes and micro-vasculature as often (79 vs 91%; p=0.002 resp. 68 vs 81%; p=0.015). There was no difference in median OS between the two groups (18.1 vs 19.1 months; p=0.064). Multvariate analysis confirmed that vascular invasion (HR 1.62, 95% CI 1.13-2.35; p=0.010) and recurrence rate (HR 2.4, 95% CI 1,73-3.45; p<0.001) were independent predictors of OS. Conclusion: In this large western single center cohort study, there was no difference in OS between mal-IPMN and PDAC, even though micro-vascular invasion and recurrence rate were less ominous in the mal-IPMN group and independent predictors of OS.

Therapeutic effect of whole brain radiotherapy on advanced NSCLC between EGFR TKI-na\xefve and TKI-resistant

BackgroundThe development of epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) has dramatically improved the prognosis of patients with EGFR-mutant non-small-cell lung cancer (NSCLC). The purpose of this study is to investigate the clinical outcome with or without EGFR-TKI resistance before WBRT and the sequence between EGFT-TKIs and whole brain radiotherapy (WBRT) of EGFR-mutant NSCLC patients who developed multiple brain metastases (BMs).Patients and methodsThree hundred forty-four EGFR-mutant NSCLC patients with multiple BMs were reviewed. Enrolled patients were divided into TKI-naïve group and TKI-resistant group. The intracranial progression-free survival (PFS) and overall survival (OS) were analyzed via the Kaplan-Meier method.ResultsFor patients with multiple BMs treated by WBRT, the median intracranial PFS and OS were longer in the TKI-naïve group than those in the TKI-resistant group, but there were no statistically significant between two groups (Intracranial PFS: 7.7 vs. 5.4 months, p = 0.052; OS: 11.2 vs. 9.2 months, p = 0.106). For patients with Lung-molGPA 0–2, no significant differences in median intracranial PFS (6.2 vs. 5.2 months, p = 0.123) and OS (7.8 vs. 6.7 months, p = 0.514) between TKI-naïve and TKI-resistant groups. For patients with Lung-molGPA 2.5–4, intracranial PFS: 12.8 vs. 10.1 months; OS: 23.3 vs. 15.3 months.ConclusionsOur study found that there were no difference in intracranial PFS and OS in all patients between the two groups of TKI-naïve and TKI-resistant. But for patients in subgroup of Lung-molGPA 2.5–4, there were a better intracranial PFS and OS in TKI-naïve group.