Median OS For Pts Research Articles

Abstract PO2-06-12: Patients with metastatic triple-negative breast cancer who receive trilaciclib prior to cytotoxic chemotherapy exhibit improved survival after receiving subsequent anticancer therapy

Abstract Background In an open-label, randomized, phase 2 trial in patients (pts) with metastatic triple-negative breast cancer (mTNBC; NCT02978716), administering trilaciclib prior to gemcitabine plus carboplatin (GCb) significantly prolonged overall survival (OS; a key secondary endpoint) versus administering GCb alone (median 19.8 vs 12.6 months; hazard ratio 0.37; P < 0.0001), with a nonsignificant trend toward improved progression-free survival (median 9.0 vs 5.7 months; hazard ratio 0.62; P = 0.13; Tan et al. Clin Cancer Res. 2022). Given murine data suggesting trilaciclib may preserve the long-term function of hematopoietic stem and progenitor cells (He et al. Sci Transl Med. 2017) and improve T-cell memory (Goel et al. Nature. 2017; Lelliott et al. Cancer Discov. 2021; Heckler et al. Cancer Discov. 2021), we examined survival of pts with mTNBC who received subsequent lines of therapy after receiving GCb with or without trilaciclib. Methods In the phase 2 trial, pts with ≤ 2 prior chemotherapy regimens for locally recurrent or metastatic TNBC were randomized 1:1:1 to receive GCb on days 1 and 8, trilaciclib prior to GCb on days 1 and 8, or trilaciclib alone on days 1 and 8 and prior to GCb on days 2 and 9. The 2 trilaciclib arms were combined for this analysis. To determine if trilaciclib improved outcomes in pts who received additional therapy after GCb, a post hoc survival analysis was performed using data from pts who received any subsequent anticancer therapy (SACT). Results In the subanalysis of data from pts with mTNBC who received any SACT after the phase 2 trial, clinical characteristics such as demographics, disease variables, duration from study treatment to first SACT, and type of SACT were balanced between the trilaciclib (n = 43) and placebo (n = 20) arms. The most common SACTs were gemcitabine, capecitabine, eribulin, taxanes, checkpoint inhibitors, carboplatin, and anthracyclines. Median OS in pts who had previously received trilaciclib was 32.7 months versus 12.8 months in those who had received placebo, with increasing separation of survival curves over time. Median OS from start of first SACT was 17.4 months in the trilaciclib arms vs 5.8 months in the placebo arm. Improved survival and sustained separation of curves was also observed in pts unable to receive SACT (trilaciclib, n = 25; placebo, n = 14), although the magnitude of benefit was smaller (median 9.4 vs 5.4 months). Mechanistic in vivo murine and in vitro human studies are underway to examine the effect of trilaciclib on the generation of memory T cells. These studies will assess the preferential differentiation of specific memory T-cell subsets along with in vivo assessment of memory T-cell responses following a rechallenge. Further data will be presented to evaluate whether the enhanced generation and preservation of a memory T-cell pool is supportive of improved outcomes in pts receiving SACT. Conclusions Data from the phase 2 study suggest that pts with mTNBC who received trilaciclib prior to cytotoxic chemotherapy have prolonged survival, which is notably improved for pts who are able to receive SACT following discontinuation of trilaciclib. The survival benefit from trilaciclib extends to pts who subsequently received immune checkpoint inhibitors and/or chemotherapy, and also to those who did not receive any SACT. Improved OS in pts receiving trilaciclib may be associated with protection of hematopoietic stem and progenitor cells and formation of a memory T-cell pool, which is critical for long-term immune surveillance and in eliciting rapid recall responses. OS will be evaluated in pts with mTNBC in the ongoing phase 3 trial of trilaciclib prior to GCb (PRESERVE 2; NCT04799249) and phase 2 trial of trilaciclib prior to sacituzumab govitecan (NCT05113966). Citation Format: Shom Goel, Joyce O'Shaughnessy, Kun-Hui Lu, Andrew Beelen, Symantha Melemed, John Yi, Michael Danso, Antoinette Tan. Patients with metastatic triple-negative breast cancer who receive trilaciclib prior to cytotoxic chemotherapy exhibit improved survival after receiving subsequent anticancer therapy [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 PO2-06-12.

Abstract PO2-04-04: Trastuzumab deruxtecan for the treatment of patients with HER2-positive breast cancer with brain and/or leptomeningeal metastases: an updated overall survival analysis using data from a multicenter retrospective study (ROSET-BM)

Abstract Background: ROSET-BM (UMIN000044995) was a multicenter, retrospective chart review study of patients (pts) who received trastuzumab deruxtecan (T-DXd) treatment for HER2-positive (HER2+) metastatic breast cancer (MBC) with brain metastases (BM) and/or leptomeningeal carcinomatosis (LMC). Primary results (data cutoff, October 31, 2021) were presented at SABCS2022 (median progression-free survival [PFS], 16.1 months; 1-year overall survival [OS] rate, 74.9%; and median follow-up duration, 11.2 months). To confirm the long-term effectiveness of T-DXd in HER2+ MBC pts with BM and/or LMC, we conducted an updated analysis using additional 1-year follow-up data. Methods: Pts who started T-DXd treatment between May 25, 2020, and April 30, 2021, were registered for ROSET-BM. For this updated OS analysis, the extended observation period ended on October 31, 2022. OS, PFS, and time to treatment failure (TTF) were evaluated. Median survival times and 95% CIs were calculated using the Kaplan–Meier method. In addition, prespecified and exploratory subgroup analyses were performed based on patient background characteristics. Univariate and multivariate Cox proportional hazards regression models were used to evaluate baseline prognostic factors for OS. Results: 104 pts from 62 institutions were included in this updated OS analysis. Median duration of follow-up was 20.4 months. Median number of prior lines of therapy was 4 (range, 1–15). Median time from first diagnosis of MBC to first administration of T-DXd was 37.5 months. Median time from first diagnosis of BM to first administration of T-DXd was 18.9 months. The prevalence of active BM, stable BM, LMC, and unclassified (image not evaluated) was 64.4% (n=67), 11.5% (n=12), 18.3% (n=19), and 5.8% (n=6), respectively. Median OS was not reached (NR) among all pts (1-year OS rate, 74.8%; 2-year OS rate, 56.0%). Subgroup analyses showed that median OS in pts with active BM was 27.0 months (95% CI, 16.4 to NR) and that median OS was NR in pts with stable BM or LMC (2-year OS rate for pts with stable BM, 71.6%; 2-year OS rate for pts with LMC, 61.6%). The results of univariate and multivariate analyses for OS showed no relevant baseline prognostic factors. Among all pts, median PFS was 14.6 months (95% CI, 10.6–20.8). Subgroup analyses showed that in pts with active BM, stable BM, and LMC, median PFS was 13.2 months (95% CI, 10.0–20.3), NR (95% CI, 5.3 to NR), and 17.5 months (95% CI, 8.3–22.1), respectively. Among all pts, median TTF was 9.3 months (95% CI, 6.3–11.8). The most common event and adverse event leading to discontinuation of T-DXd was progressive disease (37 pts, 35.6%) and interstitial lung disease (ILD; 24 pts, 23.1%), respectively. Median time to onset of an ILD event was 5.3 months (range, 0.7–20.0). ILD was grade 1 in 14 pts (13.5%), grade 2 in 3 pts (2.9%), grade 3 in 5 pts (4.8%), grade 4 in 2 pts (1.9%), and grade 5 in 0 pts. The Table summarizes the primary and updated results of ROSET-BM. Conclusion: The updated OS results of this retrospective chart review show that T-DXd has promising effectiveness in HER2+ MBC pts with long-term and heavily pretreated BM and LMC. This study was funded by Daiichi Sankyo Co., Ltd. Primary and updated results from the ROSET-BM study The updated results show that T-DXd has promising effectiveness in HER2+ MBC pts with long-term and heavily pretreated BM and LMC. Citation Format: Takashi Yamanaka, Naoki Niikura, Takahiro Nakayama, Mitsugu Yamamoto, Kazuo Matsuura, Kenichi Inoue, Sachiko Takahara, Hironori Nomura, Shosuke Kita, Miki Yamaguchi, Tomoyuki Aruga, Nobuhiro Shibata, Akihiko Shimomura, Yuri Ozaki, Shuji Sakai, Daisuke Takiguchi, Takehiko Takata, Armin Bastanfard, Kazuhito Shiosakai, Junji Tsurutani. Trastuzumab deruxtecan for the treatment of patients with HER2-positive breast cancer with brain and/or leptomeningeal metastases: an updated overall survival analysis using data from a multicenter retrospective study (ROSET-BM) [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 PO2-04-04.

Validation of the Composite Complete Response (cCR) Definitions in the International Working Group (IWG) 2023 Criteria in Patients (Pts) with Higher-Risk Myelodysplastic Syndromes/Neoplasms (HR-MDS) Treated with Hypomethylating Agents (HMA) - a Large, Multicenter, Retrospective Analysis from the Validate Database

JPB and TK are co-first authors; RK and AMZ are co-senior authors Introduction: Efficacy of therapies used in HR-MDS pts has long been assessed using IWG 2006 MDS criteria, but important limitations in clinical utility and practical application of these criteria have become apparent. The revised IWG response criteria for HR-MDS were proposed in 2023 (Zeidan et al., Blood 2023) were proposed to address these gaps. IWG 2023 re-defined CR by lowering hemoglobin (Hb) threshold from 11 to 10 g/dL and bone marrow [BM] blasts from ≤5% to <5%. Further, CR with partial hematologic recovery (CRh; <5% BM blasts, no Hb threshold, platelets ≥50 × 10 9/L; neutrophils ≥0.5 × 10 9/L; peripheral blood [PB] blasts 0%), CR with limited count recovery (CR-L; <5% BM and 0% PB blasts + PB parameters for CR met in 1 [CRuni] or 2 lineages [CRbi]), and CR equivalent (CRequ; defined for pts with baseline BM of <5%.) were all proposed as provisional endpoints. Per IWG 2023 hierarchical response assessment, if a pt met criteria for both CR-L and CRh, they would be recorded as CR-L. We sought to validate the IWG 2023 definitions of cCR (CR+CR-L+CRh+CRequ) in a large, multi-center dataset of HR-MDS pts who received HMAs. Methods: The VALIDATE database includes HR-MDS pts treated with HMA-based therapies in frontline setting from 14 specialized centers. HR-MDS was defined as IPSS ≥1.5 or IPSS-R >3.5 (n=213 pts excluded). Pts were excluded (N=90) if age at diagnosis was <18 years, BM blasts ≥20% or unknown at HMA initiation, or if survival status, follow-up time, HMA type or initiation date were unknown. To preserve validity of response assessments, pts also were excluded (N=290) if no BM evaluation was performed or if first BM assessment was >180 days after HMA initiation, except in cases of overt disease progression. Best responses were assessed based on IWG 2006 and 2023 criteria. Kaplan-Meier analysis estimated OS from HMA initiation, and the log-rank test was used to compare subgroups. Cox multivariable regression models identified predictors of OS. This study was supported by an independent research grant from AbbVie. Results: Of 1,223 pts in VALIDATE database, 629 were met eligibility. Median age was 68 years, 27.7% and 27.4% were red blood cell and platelet transfusion-dependent, respectively, 38.1% had TP53 mutations, and 45.3% underwent allogeneic transplantation (allo-HCT). Most pts (71.6%) received HMA monotherapy (51.7% azacitidine, 19.9% decitabine), while 28.4% received HMA-based combinations. Median duration of therapy was 4 cycles (Range: 1-94). Median OS of different subgroups pts are shown in Figure 1. Median OS for pts with IWG 2023-defined cCR (CR+CR-L+CRh+CRequ; N = 230) was 26.5 months (mo; 95% CI: 20.7 - 32.2 mo) vs 14.3 mo (95% CI: 12.5 - 16.9 mo) for pts who did not achieve cCR (p=0.002). Median OS for pts who achieved IWG 2023-defined CR (N = 90) was 29.8 (95% CI: 23.1 - 41.8) vs. 26.4 mo (95% CI: 22.0 - 41.3) for IWG 2006-defined CR (p=0.71). The 124 pts (19.7%) who achieved CR-L had a median OS of 26.4 mo (95% CI: 17.6 - 36.2 mo); of those 67 pts achieved CRbi and had a median OS of 29.1 mo (95% CI: 20.7 - not reached), while 57 pts achieved CRuni and had a median OS of 18.7 mo (95% CI: 15.5 - 54.4 mo), with no significant difference in OS between CRbi and CRuni (Hazard ratio: 1.24; 95% CI: 0.78-1.98, p=0.71). Given the hierarchical prioritization of CR-L designation over CRh in IWG 2023 if a pt meets both response definitions, only 6 pts achieved CRh which precluded a reliable estimate of their OS. Similarly, CRequ was achieved only in 10 pts limiting a reliable assessment of OS in these pts. In a multivariable Cox model that adjusted for sex, HMA type, age, allo-HCT, complex karyotype, TP53 mutation, and IPSS-M risk group, achieving a cCR per IWG 2023 criteria was statistically significantly associated with improved OS was associated with improved OS compared to those who did not achieve cCR (HR: 1.64; 95% CI: 1.30 - 2.08; p<0.001, Figure 2). Discussion: In this real-world analysis of HR-MDS pts treated with HMA-based therapy, cCR according to IWG 2023 were associated improved OS. In particular, CR and CRL (including CRbi and CR uni) were associated with improved OS, supporting their inclusion in the overall response rate in clinical trials. The number of pts who achieved CRh and CRequ was too small to reliably assess their specific association with OS. Additional pts are being added to the database and detailed analyses will be presented in the meeting.

17th International Conference on Malignant Lymphoma, Palazzo dei Congressi, Lugano, Switzerland, 13 - 17 June, 2023.

Introduction: The ataxia–telangiectasia mutated (ATM) gene plays an important role in the cellular response to DNA damage. Whether different types of ATM aberrations (mutation and/or deletion of (del)11q) differentially affect survival in mantle cell lymphoma (MCL) has not yet been reported. Methods: We analyzed 160 consecutive MCL patients (pts) treated in two Czech university centers (Prague, Olomouc) from 11/2006 to 12/2021. Both fluorescence in situ hybridization (FISH) and next generation sequencing (NGS, Illumina), were performed in all pts to identify ATM and TP53 gene aberrations on tumoral tissue (peripheral blood, bone marrow); the cutoff value for ATM and TP53 mutation was 3% variant allele frequency. Peripheral blood and/or bone marrow had at least 5% MCL involvement as analyzed by flow cytometry. Variables were compared by chi-squared test. Kaplan-Meier method was used to calculate the probabilities of progression and overall survival (PFS, OS); the log rank test was used for univariate comparisons of survival curves. PFS and OS were calculated from the date of diagnosis. Results: The median age at diagnosis was 67 (30-87) years. All pts had advanced disease (IV). MIPI score was low, intermediate and high in 15.6%, 26.3% and 58.1% pts, respectively. Treatment approaches used were as follows: watch and wait in 5.0%, R-CHOP/R-CHOP-like in 50.6%, intensive R-HDAC-containing in 34.4% and non-anthracycline/palliative regimen in 10.0% of pts. Complete and partial response was achieved in 56.3% and 21.9% of pts, respectively. Stable and progressive disease was observed in 13.1% of pts. Almost 29% of pts underwent autologous stem cell transplant. Sixty percent of pts received rituximab maintenance. Overall, 71 (44.4%) and 68 (42.5%) pts had ATM and TP53 aberration(s) (del/mut/del+mut), respectively. Of these, 20 (12.5%) pts had aberrations in both genes. Disruption of ATM gene was related to B-symptoms (p≤0.005). Age, sex, ECOG PS, cytomorphology, Ki67 index, MIPI and treatment response did not correlate with ATM aberration. With a median follow-up of 3.8 years, 2-year PFS and 2-year OS in all pts was 58.1% and 74.6%, respectively. Median PFS in pts with ATM mutation, ATM deletion and ATM+TP53 aberration was not reached, 3.3 and 0.7 years, respectively (p ≤ 0.005). Median OS in pts with ATM mutation, ATM deletion and ATM+TP53 aberration was not reached, 5.6 and 0.9 years, respectively (p ≤ 0.005). No significant difference in OS was found between ATM mutated and wild-type pts. (Survival graph below) Keywords: aggressive B-cell non-Hodgkin lymphoma, diagnostic and prognostic biomarkers, indolent non-Hodgkin lymphoma The research was funded by: IGA_LF_2023_005, MH CZ DRO-VFN64165, IGA_LF_2023_010, MH_CZ-DRO (FNOL, 00098892) No conflicts of interests pertinent to the abstract.

A Phase I/II Study of Combination of Azacitidine, Venetoclax and Pevonedistat in Patients with Newly-Diagnosed Secondary Acute Myeloid Leukemia (AML) and Myelodysplastic Syndrome (MDS) with Hypomethylating Agent (HMA) Failure

Background: Pevonedistat (PEV) is an inhibitor of NEDD8-activating enzyme (NAE) which is critical for degradation of several cellular proteins essential for tumor growth and survival. The combination of azacitidine (AZA) and venetoclax (VEN) is approved for patients (pts) with newly diagnosed (ND) AML who are unsuitable for intensive chemotherapy, and clinical studies show preliminary efficacy with AZA+VEN in higher risk MDS pts. We evaluate the efficacy and safety of the combination of AZA, VEN, and PEV in ND secondary AML (s-AML) and in MDS after HMA failure. Methods: This phase 1/2 trial enrolled pts with ND s-AML, including therapy-related AML (t-AML), AML from prior MDS or chronic myelomonocytic leukemia (CMML) or myeloproliferative neoplasm (MPN), or AML with dysplasia in ≥50% cells in ≥2 myeloid lineages (MRC). A second arm enrolled pts with MDS or CMML that had progressed on prior HMA therapy. Pts had to have a performance status ≤2, total bilirubin ≤1.5 x upper limit of normal (ULN), ALT/AST ≤2.5 x ULN, and creatinine clearance ≥30 mL/min. Pts in AML arm may have received prior HMA for preceding hematologic malignancy. In both AML and MDS/CMML cohorts, pts received AZA 75 mg/m2 SC/IV on days 1-7 and PEV 20 mg/m2 IV on days 1, 3 and 5 on every 28 day-cycle. In AML cohort, VEN was given on days 1-28 in cycle 1 and days 1-21 on cycle 2+. In MDS/CMML cohort, VEN was given on days 3-14 in cycle 1 and days 1-14 on cycle 2+. In initial phase 1 portion of the study (AML cohort only), VEN at max dose 200 mg and 400 mg were explored. Results: Between 3/2019 and 8/2021, 32 pts with AML (10 t-AML, 22 AML from MDS/CMML/MPN, 4 MRC) and 8 pts with MDS/CMML post-HMA failure (6 with MDS, 2 with CMML) were treated (Table). In the AML cohort, the median age was 74 years, with 14 pts (44%) ≥75 years of age. Cytogenetics was adverse in 21 pts (66%), and adverse risk mutations, including TP53, RUNX1, and ASXL1 were present in 34%, 31%, and 22%, respectively. 17 pts (53%) had treated secondary AML (ts-AML; i.e. prior exposure to HMA or chemotherapy for preceding myeloid neoplasm). The overall response rate (ORR, defined as CR+CRi+MLFS) was 75%, with CR in 15 pts (47%), CRi in 6 pts (19%), and MLFS in 3 pts (9%). One pt achieved PR (3%). 78% of pts achieved best response after 1 cycle of therapy (range, 1-4 cycles to best response). Among 21 pts with CR/CRi, 10 pts (48%) achieved MRD negativity by flow cytometry. 14/21 pts (67%) with poor-risk cytogenetics responded, compared to 10/11 pts (91%) with non-poor cytogenetics. 9/11 pts (82%) with TP53-mutated AML responded. 11/17 pts (65%) with ts-AML responded, compared with 13/15 pts (87%) who did not have ts-AML. With median follow up of 20 months (mos) for the AML cohort, the median OS was 8.2 mos and median relapse-free survival (RFS) was 7.4 mos. 5 pts proceeded to transplant in first remission. The median OS for pts with adverse cytogenetics was 6.8 mos and was not reached in pts without adverse cytogenetics (1-year OS of 70%). The median OS for pts with TP53-mutated AML (n=11) was 8.1 mos, pts with inv(3) (n=4) was 3.8 mos, and pts without TP53 mutation or inv(3) (n=17) was 18 mos (Figure). In MDS/CMML HMA failure cohort, the median age was 73 years. Most pts had adverse cytogenetics (50%) and were high to very high-risk by IPSS-R (87%). Overall response rate (CR+marrow CR [mCR]+HI) was 75%, with CR in 3 pts (37%), mCR in 2 pts (25%), and HI in 1 pts (13%). With a median follow up of 11 mos, the median OS was 9.9 mos. Transformation to AML occurred in 1 pt (after 11 mos). No DLTs were observed in the phase 1 portion, and VEN 400 mg daily was the recommended phase 2 dose. Myelosuppression was similar to expectations with AZA+VEN alone. Grade 3/4 non-hematologic adverse events occurring in ≥10% pts were febrile neutropenia or other infection in 75%, hypophosphatemia in 22%, and hyperbilirubinemia in 10%. The 4-week and 8-week mortality rates were 9% and 25% in AML cohort and 0% and 13% in MDS/CMML cohort, respectively. Conclusion: AZA, VEN, and PEV combination is active and well-tolerated in both ND s-AML and MDS/CMML after HMA failure. This population was enriched with very poor risk features, including a majority of pts in the AML cohort with prior HMA or chemotherapy exposure for an antecedent myeloid malignancy and 1/3 of pts with a TP53 mutation. Response rates were high across disease subgroups, although duration of responses and survival were modest in pts with historically poor risk features, including those with adverse risk cytogenetics and TP53 mutations. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Non-Canonical FLT3 Mutations (FLT3m) in Patients (Pts) with Newly Diagnosed Acute Myeloid Leukemia (AML) - Outcomes and Prognosis after FLT3 Inhibitor (FLT3i) and Venetoclax Based Regimens

Non-Canonical FLT3 Mutations (FLT3m) in Patients (Pts) with Newly Diagnosed Acute Myeloid Leukemia (AML) - Outcomes and Prognosis after FLT3 Inhibitor (FLT3i) and Venetoclax Based Regimens

Clinical and Molecular Characterization of Newly Diagnosed IDH/TP53 Co-Mutated AML and Impact of Genomically Sensitive Treatment Strategies

TP53 is mutated in ~4% of IDH mutated newly diagnosed (ND) acute myeloid leukemia (AML) and the clinical and prognostic impact of IDH/TP53 co-mutated AML is not well defined. We analyzed patients (pts) with IDH1, IDH2, and/or TP53 mutated, ND AML treated at our institution from 2012 to 2022. Multihit TP53 status was defined by 1) multiple TP53 muts 2) TP53 mut(s) and concomitant 17p/TP53 deletion 3) TP53 mut variant allele frequency (VAF)>50% suggesting mutation+ copy neutral loss of heterozygosity. Treatment (trt) regimens were classified as IDH-targeted therapy (IDHi), intensive chemotherapy (IC), or low intensity therapy (LIC). All regimens were employed with or without the addition of venetoclax (Ven) per treatment protocol. Among 628 pts with ND AML, 35 (5%) had IDH/TP53co-mut[23/35 (66%) IDH/TP53co-mut with multihit TP53], 100 (16%) had IDH1 mut, 208 (33%) had IDH2 mut, and 285 (45%) had TP53 mut [among 217/285 pts with evaluable TP53 allelic state, 185 (85%) had multihit TP53] (Table 1). Compared to pts withTP53 mut , pts with IDH/TP53co-mut had higher platelet count and higher bone marrow blasts and diploid karyotype (all p<0.05) more closely resembling features of IDHmut AML. However, pts with IDH/TP53co-mut had higher TP53 mut VAF [55%, interquartile range (IQR), (28%-67%)] compared with TP53 mut AML (33%, IQR, (10%-50%) (p=0.01). The CR/CRi rates in IDH/TP53co-mut, IDH1 mut, IDH2 mut, and TP53 mut AML were 37%,77%,72%, and 48% respectively, regardless of trt regimen. Among pts with IDH/TP53co-mut, CR/CRi rates were significantly higher in non-multihit TP53 mut than pts with multihit TP53 mut (66% vs 9%, P=0.0005). Among pts who received Ven or IDHi based therapy, pts with IDH/TP53co-mut had significantly lower CR/CRi rates compared with pts with IDH mut AML (20% vs 87% ,respectively, P<0.05). In contrast, among pts treated with IC, pts with IDH/TP53co-mut had numerically superior CR/CRi rates compared with pts with TP53 mut (75% vs 47% vs respectively, P>0.05). Among pts treated with LIC, CR/CRi rates were similar between IDH/TP53co-mut , IDH mut ,and TP53 mut AML(31% ,48%,43%,respectively). The 60-day mortality rates in IDH/TP53co-mut, IDH1 mut, IDH2 mut, and TP53 mut were 11%,10%,7%,and 19%,respectively. Hematopoietic stem cell transplant rates in IDH/TP53co-mut, IDH1 mut, IDH2 mut, and TP53 mut AML were 17%, 20%, 25%, and 12%, respectively. The median OS for pts with IDH/TP53co-mut, IDH1 mut, IDH2 mut, and TP53 mut was 8.7m,15.5m,30.3m, and 6.3m, respectively. The median OS was similar between those with IDH1/TP53co-mut and IDH2/TP53co-mut (7.8m vs. 9.5m; p=0.50). Compared to pts with IDH1 mut or IDH2 mut , those with IDH1/TP53co-mut (median OS-15.5m vs 7.8m) and IDH2/TP53co-mut (median OS-30.3 vs 9.5m) had inferior OS, respectively. There was no difference in OS between patients with IDH1/TP53co-mut and TP53 mut (median OS:7.8m vs 6.3m,p=0.3) but OS was superior in those with IDH2/TP53co-mut compared to those with TP53 mut (median OS 9.5m vs. 6.3m; p=0.03). We additionally analyzed the outcomes of IDH/TP53co-mut and TP53 mut by multi-hit TP53status. Multihit TP53status was associated with inferior survival in those with IDH/TP53co-mut (median OS:5.4m vs 41.2m, p=0.0008) (Figure-1A) and TP53 mut (median OS: 5.8 m vs 10.1m, p=0.05) compared with non-multihit status. Among pts with non-multihit TP53 status, those with IDH/TP53co-mut had superior OS compared with those with TP53 mut AML (Median OS:41.2m vs 10.1m, P=0.01)(Figure-1B) Among pts who received IDH-sensitive therapy (i.e., Ven and/or IDHi), IDH/TP53co-mut had inferior survival compared with either IDH1 mut (median OS: 5.4m vs 24.4m, p<0.05) or IDH2 mut (median OS: 5.4m vs 35.5m, p<0.05) alone. Among pts who received Ven-based therapy, OS was similar in pts with IDH/TP53co-mut and TP53 mut (median OS: 5.4m vs 5.3m, p=0.72). Among pts who received LIC, there was no difference in OS between pts with IDH/TP53co-mut and TP53 mut (median OS: 5.0m vs 6.3m, p=0.92). However, among pts who received IC, IDH/TP53co-mut had superior OS compared with TP53 mut AML (median OS: 43.8m vs 5.1m, P=0.01). Notably all pts with IDH/TP53co-mut had non-multihit TP53 status. IDH/TP53co-mut AML is a unique subtype with clinical features resembling IDHmut AML and prognosis driven by TP53 mut and the allelic status of TP53. Genomically sensitive therapies targeting both IDH and TP53 may improve the outcomes in this unique molecular subset of AML. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Prognostic effect of RAS/BRAF mutations in patients (pts) with metastatic colorectal cancer (mCRC).

191 Background: Somatic alterations in KRAS and BRAF have prognostic as well as predictive impact in pts with mCRC; however, the differential impact of various somatic alterations in these genes need further characterization. We analyzed the prognostic impact of specific somatic mutations in K RAS and BRAF in mCRC pts. Methods: We retrospectively reviewed the electronic medical records of pts with mCRC at our institution who underwent comprehensive genomic profiling (CGP) utilizing the Foundation One assay. Prevalence of genetic alterations was estimated using proportions and compared between groups using a chi-squared test. Patients were followed for survival from metastatic diagnosis until death or last follow-up, with left truncation at the time of CGP. Kaplan-Meier estimates were used to estimate overall survival, and groups were compared using a Cox-regression based likelihood ratio test. Results: 192 pts were identified - median age at diagnosis was 55 years, 62% (119/192) presented with metachronous metastatic disease, and 28% (54/192) had a rectal primary. Somatic mutations in KRAS were found in 49% (95/192) pts, and 53% (50/95) had a left sided primary (p = 0.3). Majority of the KRAS mutations localized to codon 12 (72/95 -76%), KRAS G12C comprised 12% (11/95). Median Overall Survival (mOS) of KRAS mutated pts was 3.0 years compared to 3.5 years for KRAS wild type (WT) pts (p = 0.5). Median OS of pts with different KRAS mutations were as follows: codon 12 mutations (excluding G12C) - 2.7 years; KRAS G12C – 5.2 years; non-codon 12 KRAS mutations - 4.8 years. BRAF mutations were identified in 7.8% (15/192) pts, and 67% (10/15) had a right sided primary (p = 0.062). BRAF V600E represented the most common alteration in BRAF – 87% (13/15). Patients with BRAF mutation had a mOS of 1.8 years compared to 3.1 years for BRAF WT pts (p = 0.2). Median OS of pts with different BRAF mutations were as follows: BRAF V600E – 1.8 years and BRAF non V600E - 2.1 years (p = 0.4). Conclusions: The numerically higher mOS in pts with KRAS G12C and non-codon 12 KRAS mutations merit further biologic characterization with functional assays. Individualized therapeutic strategies must be conceptualized for mCRC pts with specific RAS/BRAF mutations, considering their widely disparate prognosis and putative downstream signaling mechanisms. Dynamic molecular simulation to understand conformational changes in proteins associated with specific mutations will be pivotal to optimizing precision therapeutic strategies.

Prognostic Impact of NPM1 and FLT3 Mutations at Diagnosis and Presence of Measurable Residual Disease (MRD) after Intensive Chemotherapy (IC) for Patients with Acute Myeloid Leukemia (AML) in Remission: Outcomes from the QUAZAR AML-001 Trial of Oral Azacitidine (Oral-AZA) Maintenance

Prognostic Impact of NPM1 and FLT3 Mutations at Diagnosis and Presence of Measurable Residual Disease (MRD) after Intensive Chemotherapy (IC) for Patients with Acute Myeloid Leukemia (AML) in Remission: Outcomes from the QUAZAR AML-001 Trial of Oral Azacitidine (Oral-AZA) Maintenance

MDS-128: Azacitidine and Venetoclax Combination for Upfront Treatment of Higher-Risk Myelodysplastic Syndromes

<h3>Context:</h3> Azacitidine (aza) remains the backbone of treating higher-risk MDS patients (pts), with less than 20% of pts achieving complete response (CR) and median overall survival of 14–18 months. Ongoing studies in higher-risk MDS are assessing the role of adding venetoclax (ven) to aza in higher-risk MDS. <h3>Objective:</h3> We report, here, single-institution experience of aza/ven combination in the upfront treatment of higher-risk MDS, comparing it to historical aza alone. <h3>Design:</h3> We identified 35 pts who received aza/ven for intermediate or higher-risk MDS by R-IPSS compared to 1175 similar-risk MDS pts who historically received aza upfront therapy alone. <h3>Results:</h3> The median follow-up for the aza/ven group was 15 months (mo) compared to 93 mo for aza alone. No differences were observed in baseline demographic or disease characteristics comparing aza/ven group to aza alone except for higher rates of ASXL-1 and N-RAS somatic mutations (SM) among aza/ven treated pts. There was no difference in median OS among the two groups: median OS was 20 mo for both groups. The CR/marrow CR (mCR) rate was higher with the aza/ven combination, 71% (31%/40%), compared to 25% for aza alone (13%/12%) (p<.005). Among pts with ASXL-1 SM, the CR rate was 47% compared to 9% for aza alone (p <.005). More pts treated with aza/ven proceeded to allogeneic hematopoietic stem cell transplant (AHSCT) (40% <i>vs</i> 23%, p=.04). The median OS for pts treated with aza/ven followed by AHSCT was not reached compared to 31 mo for aza alone followed by AHSCT (p=.17). The 2-year survival rate for pts who underwent AHSCT was 90% for aza/ven compared to 51% for the aza alone group. <h3>Conclusion:</h3> Aza/ven combination is associated with higher responses overall and among ASXL-1 SM higher-risk MDS pts and encouraging early data support aza/ven as a bridge to AHSCT, with 90% 2-year OS.

Outcomes in patients (pts) aged ≥65 years in the phase 3 ASCENT study of sacituzumab govitecan (SG) in metastatic triple-negative breast cancer (mTNBC).

1011 Background: Approximately 20% of pts diagnosed with TNBC are aged ≥65 y. Often, older pts are less fit for chemotherapy due to a greater rate of comorbidities, increased use of medications, and pre-existing frailty or functional loss. SG is an antibody-drug conjugate composed of an anti–Trop-2 antibody coupled to the cytotoxic SN-38 payload via a proprietary, hydrolyzable linker. The landmark phase 3 ASCENT study (NCT02574455) showed improved outcomes with SG vs single-agent chemotherapy of physician’s choice (TPC) in pts with relapsed/refractory mTNBC (median progression-free survival [PFS], 5.6 vs 1.7 mo; median overall survival [OS], 12.1 vs 6.7 mo). Here we assess the impact of age on the efficacy and safety of SG in ASCENT. Methods: Pts with mTNBC refractory/relapsing after ≥2 prior chemotherapies were randomized 1:1 to receive SG (10 mg/kg IV on days 1 and 8, every 21 days) or TPC (capecitabine, eribulin, vinorelbine, or gemcitabine) until disease progression/unacceptable toxicity. Primary endpoint was PFS per RECIST 1.1 by independent review in brain metastases-negative (BMNeg) pts. Safety outcomes were assessed in all treated pts. This prespecified subgroup analysis assessed the impact of age (pts ≥65 y) on PFS, OS, and safety. Results: Of 529 pts enrolled, 468 were BMNeg (median age, 54 y); of these, 44/235 pts (19%) who received SG and 46/233 pts (20%) who received TPC were aged ≥65 y. SG treatment improved median PFS vs TPC in pts ≥65 y (7.1 vs 2.4 mo; HR, 0.22; 95% CI, 0.12-0.40). SG vs TPC treatment also improved median OS in pts ≥65 y (15.3 vs 8.2 mo; HR, 0.37; 95% CI, 0.22-0.64). Treatment with SG vs TPC resulted in higher ORR (50% vs 0%) and clinical benefit rate (CBR, 61% vs 9%) in pts ≥65 y. Of the 7 pts ≥75 y who received SG, 2 had partial response, 4 had stable disease [SD], and 1 had SD &gt; 6 mo as best response. In pts &lt; 65 y, median PFS for SG vs TPC was 4.6 vs 1.7 mo (HR, 0.46; 95% CI, 0.35-0.59), and median OS was 11.2 vs 6.6 mo (HR, 0.50; 95% CI, 0.40-0.64), respectively; the ORR and CBR were 31% vs 6% and 41% vs 9%, respectively. Pts ≥65 y treated with SG vs TPC had similar rates of all grade and grade ≥3 treatment-emergent adverse events (TEAEs). TEAEs leading to dose reduction were similar in pts ≥65 y in the SG vs TPC arms (35% vs 33%) and were lower in pts &lt; 65 y (19% vs 24%). Key treatment-related TEAEs leading to dose reduction in pts ≥65 y in the SG vs TPC arms were neutropenia (including febrile neutropenia; 14% vs 25%), fatigue (10% vs 4%), diarrhea (6% vs 0%), and nausea (4% vs 0%). TEAEs leading to treatment discontinuation with SG vs TPC were low in pts ≥65 y (2% vs 2%) and &lt; 65 y (5% vs 6%). There were no treatment-related AEs leading to death in any SG-treated age group. Conclusions: Irrespective of age, pts who received SG had a significant survival benefit vs TPC, with a tolerable safety profile. Proactive AE monitoring and management will allow optimal therapeutic exposure to SG in older pts. Clinical trial information: NCT02574455 .

Clinical outcomes in patients (pts) with a history of central nervous system (CNS) metastases receiving talazoparib (TALA) or physician’s choice of chemotherapy (PCT) in the phase 3 EMBRACA trial.

1090 Background: In the EMBRACA trial (NCT01945775) of pts with germline BRCA1/2-mutated HER2-negative locally advanced/metastatic breast cancer (ABC), the poly(ADP-ribose) polymerase (PARP) inhibitor TALA significantly improved progression-free survival (PFS) vs PCT (8.6 vs 5.6 mo; HR [95% CI] 0.54 [0.41-0.71]; P &lt; 0.0001). Patient-reported outcomes favored TALA, and most common adverse events included anemia, fatigue, and nausea. Previous subgroup analyses found that pts with a history of CNS metastases had improved PFS for TALA vs PCT (HR [95% CI] 0.32 [0.15-0.68]; P = 0.0016) and improved objective response rate (ORR) 63.2% vs 15.8%, respectively (odds ratio [95% CI] 8.95 [1.86-52.26]; P = 0.0013). This retrospective subgroup analysis further explored the clinical characteristics and outcomes in pts with a history of CNS metastases in EMBRACA. Methods: Pts were randomized 2:1 to TALA or PCT. Pts with adequately treated and stable CNS metastases not requiring corticosteroids were included. This analysis assessed intracranial ORR and best overall response (BOR) based on investigator assessment per RECIST 1.1 in pts with intracranial disease at baseline (data cutoff 15-Sep-17), and overall survival (OS; data cutoff 30-Sep-19). Results: In the intent-to-treat (ITT) population, 63 pts (43/287 [15.0%] TALA and 20/144 [13.9%] PCT) had a history of CNS metastases, of which 33 (11.5%) pts (TALA) and 15 (10.4%) pts (PCT) had intracranial disease at baseline. Additional baseline characteristics are shown in the table. Intracranial ORR in pts with intracranial disease at baseline and unconfirmed complete or partial response was 18.2% (TALA) vs 20.0% (PCT) (odds ratio [95% CI] 0.78 [0.13-5.80]; P = 0.765). In pts with intracranial disease at baseline, an intracranial BOR of stable disease was 69.7% for TALA vs 33.3% for PCT. Median OS in pts with a history of CNS metastases was 12.9 mo (95% CI 9.4-15.6) for TALA and 13.4 mo (95% CI 8.8-17.6) for PCT (HR [95% CI] 0.67 [0.37-1.2]; P = 0.1936 [stratified log-rank test]). In the safety population ([n = 43, TALA]; [n = 19, PCT]), median treatment duration (range) with TALA was 5.0 (0.1-36.0) mo compared with 2.1 (0.4-6.9) mo for PCT. Conclusions: In this subgroup analysis, baseline characteristics between pts with a history of CNS metastases treated with TALA or PCT were comparable. More pts with intracranial disease at baseline treated with TALA vs PCT experienced stable disease. Intracranial ORR in pts with intracranial disease was 18.2% for TALA vs 20.0% for PCT. Treatment options for pts with a history of CNS metastases are limited and further investigation in larger data sets is warranted. Clinical trial information: NCT01945775 .[Table: see text]

Roleof Allogeneic Stem Cell Transplant (ASCT) in Patients (Pts) with Relapsed/Refractory (R-R) Acute Lymphoblastic Leukemia (ALL) Treated with Inotuzumab Ozogamicin (INO) in Combination with Low-Intensity Chemotherapy (mini-hyper-CVD) with or without Blinatumomab (Blina): Results from a Phase 2 Study

Roleof Allogeneic Stem Cell Transplant (ASCT) in Patients (Pts) with Relapsed/Refractory (R-R) Acute Lymphoblastic Leukemia (ALL) Treated with Inotuzumab Ozogamicin (INO) in Combination with Low-Intensity Chemotherapy (mini-hyper-CVD) with or without Blinatumomab (Blina): Results from a Phase 2 Study

Myc Expression and Tumor-Infiltrating T Cells Are Associated with Response in Patients (Pts) with Relapsed/Refractory Diffuse Large B-Cell Lymphoma (r/r DLBCL) Treated with Tisagenlecleucel in the Juliet Trial

Myc Expression and Tumor-Infiltrating T Cells Are Associated with Response in Patients (Pts) with Relapsed/Refractory Diffuse Large B-Cell Lymphoma (r/r DLBCL) Treated with Tisagenlecleucel in the Juliet Trial

Molecular dissection of normal karyotype acute myeloid leukemia.

7534 Background: Conventional cytogenetics remain one of the most important prognostic factors in acute myeloid leukemia (AML), though 50-60% of patients (pts) have normal karyotype (NK), conventionally classified as intermediate-risk, and have very heterogeneous outcomes. A fraction of mutations such as NPM1, FLT3-ITD, and CEBPa can improve risk stratification for some pts but underestimate the molecular complexity and interactions between these genes and others. Methods: Genomic and clinical data of 2,793 primary AML (pAML) pts were analyzed. A panel of 35 genes that are commonly mutated in AML and myeloid malignancies and have shown to impact OS was included. Correlation of each mutation with others and their impact on OS were evaluated. OS was calculated from the date of diagnosis to date of death or last follow-up. Results: Of 2,793 pts with pAML, 1,352 (48%) had NK and were included in the final analysis. The median age was 55 years (range, 18-93). The median number of mutations/sample was 3 (range, 0-7). The most commonly mutated genes were: NPM1 (49%), DNMT3A (37%), FLT3-ITD (24%), CEBPa (19%), TET2 (17%), IDH2 (17%), and RUNX1 (15%). In univariate Cox regression analysis, mutations in NPM1 (HR 0.81, p =0.008), and CEBPa (single mutant, HR 0.8, double mutant, HR 0.69, p&lt; 0.001, respectively) were associated with longer OS, while mutations in DNMT3a (HR 1.26, p =0.003), FLT3-ITD (HR 1.49, p&lt; 0.001), TET2 (HR 1.26, p =0.02), RUNX1 (HR 1.36, p =0.003), SRSF2 (HR 1.58, p &lt;0.001), IDH1 (HR 1.29, p &lt;0.001), and ASXL1 (HR 1.89, p &lt;0.001) were associated with shorter OS. A total of 67% of pts had NPM1, DNMT3A, and FLT3-ITD mutated alone or in combination with each other. The median OS for pts with NMP1Mut/ DNMT3AWT/FLT3-ITDWT was 99.1 months(m), NMP1Mut/DNMT3AMut /FLT3-ITDWT 54.8m, NMP1Mu t/DNMT3AWT/FLT3-ITDMut 42.3m, NMP1Mut/DNMT3AMut/FLT3-ITDMut 13.4m, NMP1WT/DNMT3AMut/FLT3-ITDMut 13.1m, and NMP1WT/DNMT3AWT/FLT3-ITDWT (triple negative) 32.7m. The median OS for pts with 0-2 mutations/sample was 59.3m, compared to 34.1m for pts with 3-4 mutations, and 16.1m for pts with &gt; 5 mutations ( p&lt; 0.001). Conclusions: We propose a simplified and robust approach to risk stratify AML pts with NK based on the mutational status of NPM1, DNMT3A, FLT3-ITD (alone or in combination with each other), CEBPa, and the number of mutations/sample.

Abstract P4-10-08: Absolute lymphocyte count (ALC) is a predictor of eribulin benefit in advanced or metastatic breast cancer (MBC)

Abstract Objective: This post hoc analysis assessed predictors for OS in patients (pts) treated with eribulin using data from 2 phase 3 studies: EMBRACE and Study 301. Background: Eribulin is a nontaxane synthetic inhibitor of microtubule dynamics approved for use in locally advanced or metastatic breast cancer after two previous lines of chemotherapy. In EMBRACE, 508 pts were randomized to eribulin monotherapy and 254 pts to the treatment of physician’s choice (TPC). Median OS of pts in the eribulin arm was significantly better than the TPC arm but no significant difference was seen in progression-free survival (PFS) by independent review. Study 301 randomized 554 pts to eribulin and 548 pts to capecitabine; no significant difference was seen in PFS. Kashiwagi et al, PloS one, 2017, suggested that cells such as tumor-infiltrating lymphocytes (TILs) in the tumor microenvironment may be a predictive marker of eribulin efficacy—pts with a high number of TILs had significantly longer PFS than pts with low TIL counts. Miyagawa et al, Clin Breast Cancer, 2018, found neutrophil-to-lymphocyte ratio to be significantly associated with longer PFS with eribulin. Our analysis focused on ALC, a peripheral immune parameter. Methods: Pts from EMBRACE with baseline ALCs were included in this analysis. The Kaplan-Meier method was used to estimate OS distribution. Interaction analysis of OS was performed between treatment and baseline ALCs to explore differential cutoff values. Hazard ratios (HR) were estimated from the stratified Cox proportional hazard model with the randomization stratification factors: HER2/neu status, prior capecitabine treatment, and geographical region. Multivariate analyses for baseline factors were performed using the Cox proportional hazard model to identify predictors and to confirm baseline ALC effect for OS. Similar methods were used to analyze associations between baseline ALC and OS in Study 301. Results: EMBRACE included 500 pts in the eribulin arm and 251 in the TPC arm with an evaluable baseline ALC. Pts with high baseline ALC consistently experienced greater eribulin benefit vs pts with low baseline ALC across cutoff values from 1300-1750/μL. The greatest difference was observed at the cutoff value of 1500/μL. Median OS was higher in pts with baseline ALC ≥1500/µL vs baseline ALC &amp;lt;1500/µL in the eribulin arm (15.6 vs 11.6 months) but not in the TPC arm (Table). The eribulin group showed prolonged OS compared with the TPC group in pts with ALC ≥1500/µL (HR 0.586; 95% CI: 0.437-0.784; P&amp;lt;0.001). There was no significant difference by treatment for ALC &amp;lt;1500/µL (HR 1.002; 95% CI: 0.800-1.253; P=0.989). Study 301 included 553 pts on eribulin and 547 pts on capecitabine. Similar results were observed in the eribulin arm, median OS was higher in pts with baseline ALC ≥1500/µL vs pts with baseline ALC &amp;lt;1500/µL (19.6 vs 14.6 months). There was a treatment effect favoring eribulin vs capecitabine at ALC ≥1500/µL but not at ALC &amp;lt;1500/µL. Conclusion: ALC at baseline may potentially be an independent predictor for longer OS in pts treated with eribulin. This hypothesis-generating study speculates that baseline ALC may be useful in the selection of pts to be treated with eribulin. Table. Multivariate analysis of OS identified the following predictors for OS in the eribulin group: prior capecitabine, ECOG PS, HR status, number of organs involved, refractory to taxanes, and baseline ALCStudyBaseline ALCArmPatients, nMedian OS (months)HR (95% CI)EMBRACEALC ≥1500/µLEribulin19915.60.586 (0.437-0.784)TPC9211.4ALC &amp;lt;1500/µLEribulin30111.61.002 (0.800-1.253)TPC15910.3Study 301ALC ≥1500/µLEribulin23319.60.811 (0.662-0.993)Capecitabine26916.0ALC &amp;lt;1500/µLEribulin32014.60.907 (0.758-1.084)Capecitabine27812.5ALC, absolute lymphocyte count; CI, confidence interval; HR, hazard ratio; OS, overall survival; TPC, treatment of physician’s choice. Citation Format: Javier Cortes, Jose Manuel Perez-Garcia, Kenichi Nomoto, Karenza Alexis, Kenichi Saito, Yuta Yoshimura, Kenzo Muramoto, Yasuo Miyoshi. Absolute lymphocyte count (ALC) is a predictor of eribulin benefit in advanced or metastatic breast cancer (MBC) [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 P4-10-08.

Baseline features predicting receipt of chemotherapy in metastatic esophageal cancer: A National Cancer Database analysis of 12,370 patients.

316 Background: We investigated predictors for chemotherapy (CTX) and prognostic variables in a large metastatic esophageal cancer (mEC) patient data set. Methods: We interrogated the National Cancer Database between 2004-2015 and included patients (pts) with M1 disease who had known CTX status (received or did not receive CTX). Univariable and multivariable analyses were performed, and a logistic regression model was used to estimate the effect of CTX with adjustment for potential confounders. Results: We included 12,370 mEC patients with available CTX status for multivariable analyses. Predictors for CTX treatment included year of diagnosis 2010-2014 (odds ratio (OR) 1.29, 95% confidence interval (CI) 1.17-1.43), median income &gt; $46,000 (OR 1.49, 1.27-1.75), and node-positivity (OR 1.35, 1.20-1.52; all p &lt; 0.05), while female gender (OR 0.86, 0.76-0.98), black race (OR 0.76, 0.67-0.93), uninsured (OR 0.41, 0.33-0.52), and Charlson Comorbidity Index (CCI) ≥2 (OR 0.61, 0.50-0.74) predicted for lower odds of receiving CTX (all p &lt; 0.05). Median OS for pts receiving CTX was 9.53 mos (9.33-9.72) vs. 2.43 mos (2.27-2.60) with no CTX (p &lt; 0.001). Modeling the effect of CTX to OS using a time-dependent coefficient showed that CTX was associated with improved OS up to 10 months, after which there is no significant effect on OS. Independent predictors of OS included treatment at an academic center (hazard ratio (HR) 0.91, 0.87-0.94), CCI ≥2 (HR 1.16, 1.07-1.26), and uninsured status (HR 1.20, 1.09-1.31). Conclusions: We identified several predictors for receipt of CTX and OS in pts with mEC. The benefit of CTX on OS is time-dependent and favors early initiation. Focused outreach in lower income and underinsured patients is critical as receipt of CTX is associated with improved OS.

Change of clinical features and outcomes of adolescents and young adults (AYA) with colorectal cancer over time: Pooled analysis of 26,768 patients in the National Cancer Database (NCDB).

256 Background: The incidence of colorectal cancer (CRC) in younger patients (pts) is rising. The underlying etiology is unknown, and it is uncertain if disease biology and clinical features are changing over time. Methods: A retrospective study of pts data in the NCDB was performed to compare the clinicopathological features and outcomes of AYA with CRC over a 12-year period. Pts diagnosis period was dichotomized into older (2004 – 2009) and newer (2010 – 2015) eras. Uni- and multi-variable chi-square, logistic regression, and survival analyses were used for comparisons. Survival differences were assessed using Kaplan-Meier curves. Results: In total, 26,768 AYA (18-40yrs) with CRC were identified and included in the analysis: 45.8% (n = 12,268) from the older and 54.2% (n = 14,500) from the newer era. There were no differences between the 2 groups in gender distribution or levels of income and education. However, in the newer vs. older era, there was a greater proportion of non-white, non-black pts (7.2% vs. 6%; p = 0.0005) and pts diagnosed between the ages of 18-30 (21.1% vs. 18.8%; p &lt; .0001). Pts in the newer era tended to have more comorbidities (8.6 vs 7.5%; p = 0.0012), left-sided tumors (77.5% vs. 76.1%; p = 0.04), and well-differentiated histology (12.0% vs. 8.3%; p &lt; 0.0001). Newer era pts also had lower rates of metastatic disease at presentation (15.3% vs. 18.2%; p &lt; 0.001%) and nodal involvement (54.9 vs. 58.4%; p &lt; 0.001%). Median OS of pts with stage IV disease appears to have improved over time (24.1 vs. 22.5 mos; p = 0.014). After controlling for age, race, primary tumor site and grade, presence of comorbidities, and health insurance status, older era pts with stage IV CRC were at a 15.1% greater risk of all-cause death by year 5 compared to newer era pts (HRadj= 1.15 (1.07-1.24, p = 0.0001). Conclusions: Our data suggest that AYA with CRC in more recent years tend to present at a younger age and have a lower rate of metastatic disease. They also have improved survival. Further investigation of AYA disease etiology and biology are warranted. Continued efforts to increase awareness, promote early detection, and improve treatment options are essential.

Characteristics, Treatment Patterns, and Outcomes in Primary Cutaneous Gamma Delta T Cell Lymphoma (PCGDTCL): A Real World Multi-Institutional Analysis of a Rare Malignancy

Characteristics, Treatment Patterns, and Outcomes in Primary Cutaneous Gamma Delta T Cell Lymphoma (PCGDTCL): A Real World Multi-Institutional Analysis of a Rare Malignancy

Prognostic Impact of Clonal Diversity in Acute Myeloid Leukemia (AML) Treated with Intensive Chemotherapy (IC)

Prognostic Impact of Clonal Diversity in Acute Myeloid Leukemia (AML) Treated with Intensive Chemotherapy (IC)