Trend For Overall Survival Research Articles

Acquired gene alteration patterns and post-progression survival: PARADIGM study analysis.

3507 Background: In the phase 3 PARADIGM trial (NCT02394795), adding panitumumab (PAN) to FOLFOX6 improved overall survival (OS) compared with bevacizumab (BEV) in patients (pts) with RASWT mCRC. In this exploratory analysis, we investigated the role of acquired gene alterations in pts who experienced progressive disease (PD) and the impact of these alterations on post-progression survival (PPS). Methods: PPS was defined as the interval from PD to death. Pre- and post-treatment cell-free DNA (cfDNA) was analyzed using the custom PlasmaSELECT-R 91 PGDx panel (NCT02394834). PFS, OS, and PPS were compared by patterns of acquired gene alterations. Results: Among the enrolled 802 pts, 390 discontinued treatment due to PD, of which 276 (70.8%) had evaluable pre- and post-treatment cfDNA samples (PAN, 126; BEV, 150). PAN pts with acquired RTK/RAS alterations had shorter PPS than those without alterations (13.2 vs 18.8 mo, HR 1.88 [95% CI: 1.28–2.76]) with the same trend in OS. BEV pts with acquired CIMP pathway alterations had shorter PPS than those without (14.9 vs 18.6 mo; HR 1.58 [1.09–2.29]); OS had similar results. Co-occurrence of gene alterations was more frequent in PAN vs BEV (overall 52.4% vs 43.3%, RTK/RAS gene co-alterations 25% vs 10%). Co-occurrence of gene alterations resulted in shorter PPS only in PAN pts. Conclusions: Distinctive patterns of acquired gene alterations were observed in PAN- and BEV-treated pts with PD. Co-occurrence of gene alterations, particularly in the RTK/ RAS pathway, was more prevalent with PAN than BEV. Clinical trial information: NCT02394834 .

Gene fusions: A retrospective analysis of therapies and treatments of MTB patients over 7 years.

e15183 Background: Gene fusions (GF) are less common than single nucleotide variants, amplifications, and deletions, but have been suggested to be more predictive of responses to specific molecularly targeted therapies than other types of molecular alterations. We reviewed our institutional trends for overall survival in our molecular tumor board database based on the receipt of molecularly targeted therapy. Methods: We identified patients with non-hematologic malignancies and gene fusions (GF) identified by DNA based next generation sequencing (NGS) and reviewed by the Inova Schar Cancer Institute Molecular Tumor Board (ISCI MTB) between March 1, 2016 and March 1, 2023. GFs were confirmed by re-evaluation of next generation sequencing, and we determined the number of patients who received molecularly targeted therapy (RTT) specific for the GF. We evaluated overall survival (OS) in the RTT cohort and in the cohort that did not receive targeted therapy (NTT). TMPRSS fusions in prostate cancer were excluded from this analysis. Results: There were 93 patients with gene fusions in advanced staged cancers that met study criteria. Twenty-three were lost to follow up, transferred care outside ISCI, or enrolled in hospice. Of 70 stage IV patients reviewed, thirty-seven were found to have received GF targeted therapy. OS for all patients was 28.5 months. Patients in the RTT cohort had a median OS of 45 months and patients in the NTT cohort had an OS of 26.8 months (p-value = 0.16, Log-rank test). Conclusions: Targeted therapy in solid tumors with gene fusions is associated with prolonged overall survival. It is critical for MTBs to use NGS platforms that identify GF. Further studies examining OS and GF are warranted. [Table: see text]

Chromothripsis in myeloid malignancies.

Chromothripsis refers to massive genomic rearrangements developed during a catastrophic event. In total acute myeloid leukemia (AML), the incidence of chromothripsis ranges from 0 to 6.6%, in cases of complex karyotype AML, the incidence of chromothripsis ranges from 27.3 to 100%, whereas in cases of AML with TP53 mutations, the incidence ranges from 11.1 to 90%. For other types of malignancies, the incidence of chromothripsis also varies, from 0 to 10.5% in myelodysplastic syndrome to up to 61.5% in cases of myelodysplastic syndrome with TP53 mutations.Chromothripsis is typically associated with complex karyotypes and TP53 mutations, and monosomal karyotypes are associated with the condition. ERG amplifications are frequently noted in cases of chromothripsis, whereas MYC amplifications are not. Moreover, FLT3 and NPM1 mutations are negatively associated with chromothripsis. Chromothripsis typically occurs in older patients with AML with low leukocyte counts and bone marrow blast counts. Rare cases of patients with chromothripsis who received intensive induction chemotherapy revealed low response rates and poor overall prognosis. Signal pathways in chromothripsis typically involve copy number gain and upregulation of oncogene gene sets that promote cancer growth and a concomitant copy number loss and downregulation of gene sets associated with tumor suppression functions.Patients with chromothripsis showed a trend of lower complete remission rate and worse overall survival in myeloid malignancy. Large-scale studies are required to further elucidate the causes and treatments of the condition.

Adjuvant Chemotherapy After Neoadjuvant Therapy and Surgery for Non-Small Cell Lung Cancer

BackgroundThere is a dearth of data on outcomes of postoperative chemotherapy after neoadjuvant therapy followed by surgery in patients with locally advanced non-small cell lung cancer (NSCLC). The objective of this study was to compare survival outcomes in patients who did and did not receive adjuvant chemotherapy. MethodsA retrospective chart review was performed using our multicenter database to identify patients who received neoadjuvant therapy followed by surgery for clinical T3 N0 or N1-N2 resectable NSCLC between 2009 and 2016. Survival outcomes were analyzed with the Kaplan-Meier method and a Cox proportional hazards model. Propensity score matching (PSM) was used to control for selection bias in evaluation of overall survival (OS) and recurrence-free survival (RFS) by matching age, sex, smoking history, Charlson Comorbidity Index, histologic type, and pathologic nodal status and stage. ResultsThe participants were 156 patients with a median age of 65 years. The median RFS of the whole cohort was 66.3 months; OS was not reached. Before PSM, patients receiving adjuvant chemotherapy had significantly shorter RFS (hazard ratio [HR], 1.79; 95% CI, 1.13-2.82) and showed a trend for shorter OS (HR, 1.37; 95% CI, 0.78-2.39). After PSM, 50 patients were used for comparison in each group, and those receiving adjuvant chemotherapy did not have a more favorable RFS (HR, 1.33; 95% CI, 0.75-2.34) or OS (HR, 1.25; 95% CI, 0.62-2.51). ConclusionsAdjuvant chemotherapy was not associated with favorable survival outcomes in patients treated with surgery after neoadjuvant therapy for locally advanced NSCLC.

Abstract PS04-02: BRCA testing and PARP inhibitor utilization in real-world HER2-negative metastatic breast cancer

Abstract Background: PARP inhibitors (PARPi) have demonstrated progression-free survival benefits vs. chemotherapy in patients (pts) with metastatic breast cancer (mBC) and germline BRCA mutations (gBRCAm). NCCN guidelines recommend that all pts with mBC are offered gBRCAm testing to aid in systemic treatment decisions with PARPi. Understanding real-world gBRCAm testing patterns and PARPi use would be beneficial for improving clinical outcomes of pts with gBRCAm mBC. Methods: This retrospective cohort study identified pts ≥ 18 years old with HER2-negative mBC, diagnosed from 2014 to 2022 (US Flatiron Electronic Health Record database). gBRCAm testing patterns in mBC over time were examined by BC subtype (hormone receptor-positive [HR+] or triple-negative breast cancer [TNBC]) and disease stage at diagnosis [de novo or recurrent]). Timing of gBRCAm testing and subsequent initiation of first-line or later PARPi in pts with gBRCAm HR+ and TNBC mBC was assessed in pts diagnosed after 2018 when PARPi were approved in mBC. Prevalence of gBRCAm was calculated overall and by mBC subtype. Demographic and clinical characteristics were described by gBRCAm testing and PARPi initiation (yes/no). Real-world overall survival (OS) by PARPi use since mBC diagnosis was estimated using the Kaplan-Meier method and a log-rank test. Results: Of 15,006 total pts, 4654 (31.0%) had a gBRCAm test. Compared with pts who were not tested, gBRCAm-tested pts were younger at initial mBC diagnosis (median age: 53.5 vs. 62.0 years), had a shorter median disease-free interval before mBC diagnosis (821 vs. 959 days), and were less likely to have de novo mBC (28.0% vs. 31.2%). gBRCAm testing prevalence was 6.1% in the HR+ group (n=11,945) and 8.9% in the TNBC group (n=2430). gBRCAm testing rates mostly increased from 2014 to 2022 and were lowest in HR+ tumor subtypes; < 2/3 of all pts had a gBRCAm test from 2020 onwards (Table). Most pts with recurrent mBC (HR+: 68.3%; TNBC: 76.1%) were gBRCAm tested before diagnosis, whereas pts with de novo mBC were tested at a later timepoint ( > 60 days after mBC diagnosis – HR+: 48.3%; TNBC: 38.4%). Of all pts with gBRCAm diagnosed from 2018 onwards (n=187), 44.4% initiated PARPi. A higher proportion of pts with gBRCAm in the TNBC group initiated PARPi (52.9%) than in the HR+ group (42.4%). Pts with gBRCAm in the TNBC group received PARPi earlier than pts with gBRCAm in the HR+ group (mean days from mBC diagnosis to first PARPi use: 173 and 411 days, respectively). Fewer pts with de novo mBC (35.7%) initiated PARPi than pts with recurrent mBC (50.8%). With a median follow-up of 15.3 months, pts with gBRCAm initiated on PARPi had numerically longer median OS (32.3 months [95% CI: 24.2–47.4]) than PARPi non-initiators (21.4 months [95% CI:18.4–43.5]). OS results should be regarded with caution due to the small sample size (n=187). Conclusions: Despite NCCN guideline gBRCAm-testing recommendations, < 2/3 of pts with HER2-negative mBC in our study were gBRCAm tested from 2020 onwards. gBRCAm testing was lower in pts with HR+ disease and was performed at a later timepoint for pts with de novo disease. Wider and timelier implementation of gBRCAm testing to identify pts that could benefit from PARPi is warranted. Fewer pts with gBRCAm who had HR+ tumors or de novo disease received PARPi than pts with TNBC. Our data suggest that pts who initiated PARPi had numerically longer OS than PARPi non-initiators; further research into OS trends and PARPi use in gBRCAm mBC would be of interest. Editorial acknowledgment: Medical writing assistance was provided by Leigh-Ann Booth, Ph.D. from BOLDSCIENCE Inc., funded by AstraZeneca and Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, US Legal entity responsible for the study: AstraZeneca. Funding: This study was supported by AstraZeneca and Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, US, who are codeveloping olaparib. Table. gBRCAm testing rates over time in pts with HER2-negative mBC HER2-negative mBC is defined as IHC 0, or 1-positive, or IHC2-positive/ISH-negative. *Olaparib approved in mBC; †Olaparib approved in eBC. eBC, early breast cancer; gBRCAm, germline breast cancer gene mutation; HER2, human epidermal growth factor receptor 2; HR, hormone receptor; IHC, immunohistochemistry; ISH, in situ hybridization; mBC, metastatic breast cancer; pt, patient; TNBC, triple-negative breast cancer. Citation Format: Siddhartha Yadav, Sam Hillman, Linlin Luo, Weiyan Li, Jagadeswara Earla, Xiaoqing Xu. BRCA testing and PARP inhibitor utilization in real-world HER2-negative metastatic breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PS04-02.

Abstract GS03-13: Inavolisib or placebo in combination with palbociclib and fulvestrant in patients with PIK3CA-mutated, hormone receptor-positive, HER2-negative locally advanced or metastatic breast cancer: Phase III INAVO120 primary analysis

Abstract Background: More effective treatments for patients (pts) with endocrine-resistant, PIK3CA-mutated, hormone receptor-positive, HER2-negative breast cancer (HR+, HER2– BC) that prevent or overcome resistance are needed. Previous phosphatidylinositol-4,5-bisphosphate 3-kinase alpha (PI3Kα) inhibitors have a limited therapeutic window. Inavolisib is a highly potent and selective inhibitor of the PI3K catalytic subunit α isoform protein (p110α; encoded by the PIK3CA gene). In addition, inavolisib promotes the degradation of mutated p110α, which may limit toxicity. Prior preclinical data suggested substantial synergy between PI3K and cyclin-dependent kinase 4/6 inhibition plus endocrine therapy. The inavolisib first-in-human study (NCT03006172) showed that the triplet had a manageable safety profile, lack of drug–drug interactions, and promising preliminary antitumor activity. Methods: The Phase III, randomized, double-blind INAVO120 trial (NCT04191499) recruited 325 pts with PIK3CA-mutated, HR+, HER2– locally advanced/metastatic BC (LA/mBC) who relapsed during or within 12 months of adjuvant endocrine therapy completion, and who had no prior therapy for advanced BC. PIK3CA mutations were identified by central circulating tumor DNA (ctDNA) or local tissue/ctDNA analysis. Pts were randomized to inavolisib (9 mg orally once a day [PO QD] on Days 1–28 of each cycle) or placebo (PO QD) in combination with palbociclib (125 mg PO QD on Days 1–21 of each cycle) and fulvestrant (500 mg intramuscularly on Cycle 1 Days 1 and 15, and on Day 1 of each subsequent cycle). This is the first study to assess the triplet combination at maximum dose (inavolisib) or per-label dose/schedule (palbociclib/fulvestrant). The primary endpoint was investigator-assessed progression-free survival (INV-PFS). Secondary endpoints included overall survival (OS) and confirmed objective response rate (ORR). Adverse events (AEs) were graded per NCI-CTCAE v5. Results: After 21.3 months median follow-up, median INV-PFS was 15.0 months (95% confidence interval [CI] = 11.3, 20.5) with inavolisib + palbociclib + fulvestrant, and 7.3 months (95% CI = 5.6, 9.3) with placebo + palbociclib + fulvestrant (hazard ratio 0.43; 95% CI = 0.32, 0.59). Landmark INV-PFS event-free rates at 6, 12, and 18 months were 82.9%, 55.9%, and 46.2% with inavolisib, and 55.9%, 32.6%, and 21.1% with placebo. OS showed a trend in favor of inavolisib (hazard ratio 0.64; 95% CI = 0.43, 0.97; p = 0.0338 [boundary 0.0098 or hazard ratio 0.592]), with follow-up ongoing. Landmark OS event-free rates at 12 and 18 months were 85.9% and 73.7% with inavolisib, and 74.9% and 67.5% with placebo. Confirmed ORRs were 58.4% with inavolisib and 25.0% with placebo. Rates of selected Grade 3–4 AEs with inavolisib and placebo were: neutropenia at 80.2% and 78.4%; hyperglycemia at 5.6% and 0%; diarrhea at 3.7% and 0%; stomatitis and mucosal inflammation at 5.6% and 0%; and rash at 0% and 0%. The rate of discontinuation due to AEs was 6.2% for inavolisib and 0.6% for placebo. There were no treatment-related Grade 5 AEs. Conclusions: Inavolisib + palbociclib + fulvestrant demonstrated a statistically significant and clinically meaningful improvement in INV-PFS vs. placebo + palbociclib + fulvestrant in this high-risk population, and a favorable OS trend in favor of the inavolisib combination at the first interim analysis. Inavolisib + palbociclib + fulvestrant had a manageable safety profile consistent with the known safety profiles of the individual drugs (reflective of α isoform selectivity of inavolisib), and no new safety signal was identified. Inavolisib + palbociclib + fulvestrant could represent a new standard of care for pts with PIK3CA-mutated, HR+, HER2– LA/mBC. Citation Format: Komal L. Jhaveri, Seock-Ah Im, Cristina Saura, Dejan Juric, Sibylle Loibl, Kevin Kalinsky, Peter Schmid, Sherene Loi, Eirini Thanopoulou, Noopur Shankar, Guiyuan Lei, Thomas Stout, Katherine E. Hutchinson, Jennifer Schutzman, Chunyan Song, Nicholas C. Turner. Inavolisib or placebo in combination with palbociclib and fulvestrant in patients with PIK3CA-mutated, hormone receptor-positive, HER2-negative locally advanced or metastatic breast cancer: Phase III INAVO120 primary analysis [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 GS03-13.

Trends in volumes and survival after hematopoietic cell transplantation in racial/ethnic minorities

AbstractThere has been an increase in volume as well as an improvement in overall survival (OS) after hematopoietic cell transplantation (HCT) for hematologic disorders. It is unknown if these changes have affected racial/ethnic minorities equally. In this observational study from the Center for International Blood and Marrow Transplant Research of 79 904 autologous (auto) and 65 662 allogeneic (allo) HCTs, we examined the volume and rates of change of autoHCT and alloHCT over time and trends in OS in 4 racial/ethnic groups: non-Hispanic Whites (NHWs), non-Hispanic African Americans (NHAAs), and Hispanics across 5 2-year cohorts from 2009 to 2018. Rates of change were compared using Poisson model. Adjusted and unadjusted Cox proportional hazards models examined trends in mortality in the 4 racial/ethnic groups over 5 study time periods. The rates of increase in volume were significantly higher for Hispanics and NHAAs vs NHW for both autoHCT and alloHCT. Adjusted overall mortality after autoHCT was comparable across all racial/ethnic groups. NHAA adults (hazard ratio [HR] 1.13; 95% confidence interval [CI] 1.04-1.22; P = .004) and pediatric patients (HR 1.62; 95% CI 1.3-2.03; P < .001) had a higher risk of mortality after alloHCT than NHWs. Improvement in OS over time was seen in all 4 groups after both autoHCT and alloHCT. Our study shows the rate of change for the use of autoHCT and alloHCT is higher in NHAAs and Hispanics than in NHWs. Survival after autoHCT and alloHCT improved over time; however, NHAAs have worse OS after alloHCT, which has persisted. Continued efforts are needed to mitigate disparities for patients requiring alloHCT.

Clinico–pathologic factors and survival of patients with breast cancer diagnosed with de novo brain metastasis: a national cancer database analysis

PurposePatients with Breast Cancer (BC) with Brain Metastasis (BCBM) have poor survival outcomes. We aimed to explore the clinico–pathologic and therapeutic factors predicting the survival in patients with de novo BCBM using the National Cancer Database (NCDB).Patients and methodsThe NCDB was queried for patients with BC between 2010 and 2020. Survival analysis with Kaplan–Meier curves and log rank tests were used to find median overall survival (OS) in months (95% CI) across the different variables. A multivariate cox regression model was computed to identify significant predictors of survival.ResultsOut of n = 2,610,598 patients, n = 9005 (0.34%) had de novo BCBM. A trend of decreasing OS was observed with increasing age, Charlson–Deyo score (CDS), and number of extracranial metastatic sites. The highest median OS was observed in the Triple Positive and the lowest OS in the Triple Negative subgroup. Based on treatment regimen, combination of systemic therapy and local therapy achieved the highest OS. A positive trend in OS was observed in the BC subgroup analysis with targeted therapy demonstrating a survival benefit when added to systemic therapy.The multivariate cox regression model showed that age, race, ethnicity, insurance, median income, facility type, CDS, BC subtype, metastatic location sites, and treatment combinations received were significantly associated with risk of death. Receiving only local treatment for BM without systemic therapy more than doubled the risk of death compared to combining it with systemic therapy.ConclusionsThis analysis suggests that treatment of systemic disease is the major factor influencing survival in patients with BCBM. Moreover, targeted therapy with anti–HER2 increased survival when added to systemic therapy explaining the highest median OS noted in the Triple Positive subgroup.

Association of body mass index with clinical outcome of primary WHO grade 4 glioma.

The prognostic value of body mass index (BMI) in primary WHO grade 4 gliomas is not widely acknowledged. This study aims to assess the survival outcomes of patients with different BMIs. Real-world data of patients diagnosed with primary WHO grade 4 (2021 version) glioma was assessed. All 127 patients admitted in this study were administered with standard-of-care from September 2018 to September 2021. The outcomes of overall survival and progression-free survival were analyzed. The baseline characteristics of clinical features, molecular features, and secondary treatment in BMI subsets showed no significant difference. The survival analyses showed a significantly superior overall survival (OS) in the overweight group compared to the normal weight group. A trend of better OS in the overweight group compared to the obesity group was observed. The univariate Cox regression demonstrated patients of round-BMI 25 and 26 had superior OS outcomes. In this real-world setting, patients with a BMI between 24 and 28 have superior overall survival. Patients in the proper BMI range may acquire survival benefits undergoing standard-of-care of primary WHO grade 4 gliomas. The prospective studies on a larger scale on these subsets of patients are necessary to solve the paradox of BMI in glioma.

Integrated clinical and genomic models using machine-learning methods to predict the efficacy of paclitaxel-based chemotherapy in patients with advanced gastric cancer

BackgroundPaclitaxel is commonly used as a second-line therapy for advanced gastric cancer (AGC). The decision to proceed with second-line chemotherapy and select an appropriate regimen is critical for vulnerable patients with AGC progressing after first-line chemotherapy. However, no predictive biomarkers exist to identify patients with AGC who would benefit from paclitaxel-based chemotherapy.MethodsThis study included 288 patients with AGC receiving second-line paclitaxel-based chemotherapy between 2017 and 2022 as part of the K-MASTER project, a nationwide government-funded precision medicine initiative. The data included clinical (age [young-onset vs. others], sex, histology [intestinal vs. diffuse type], prior trastuzumab use, duration of first-line chemotherapy), and genomic factors (pathogenic or likely pathogenic variants). Data were randomly divided into training and validation sets (0.8:0.2). Four machine learning (ML) methods, namely random forest (RF), logistic regression (LR), artificial neural network (ANN), and ANN with genetic embedding (ANN with GE), were used to develop the prediction model and validated in the validation sets.ResultsThe median patient age was 64 years (range 25–91), and 65.6% of those were male. A total of 288 patients were divided into the training (n = 230) and validation (n = 58) sets. No significant differences existed in baseline characteristics between the training and validation sets. In the training set, the areas under the ROC curves (AUROC) for predicting better progression-free survival (PFS) with paclitaxel-based chemotherapy were 0.499, 0.679, 0.618, and 0.732 in the RF, LR, ANN, and ANN with GE models, respectively. The ANN with the GE model that achieved the highest AUROC recorded accuracy, sensitivity, specificity, and F1-score performance of 0.458, 0.912, 0.724, and 0.579, respectively. In the validation set, the ANN with GE model predicted that paclitaxel-sensitive patients had significantly longer PFS (median PFS 7.59 vs. 2.07 months, P = 0.020) and overall survival (OS) (median OS 14.70 vs. 7.50 months, P = 0.008). The LR model predicted that paclitaxel-sensitive patients showed a trend for longer PFS (median PFS 6.48 vs. 2.33 months, P = 0.078) and OS (median OS 12.20 vs. 8.61 months, P = 0.099).ConclusionsThese ML models, integrated with clinical and genomic factors, offer the possibility to help identify patients with AGC who may benefit from paclitaxel chemotherapy.

EGFR, HLA-G, CD70, c-MET, and NY-ESO1 as potential biomarkers in high grade epithelial ovarian carcinoma.

High grade epithelial ovarian carcinoma is an aggressive tumor. Treatment includes platinum therapy, however it recurs in most patients due to therapy resistance. In this project, we study the immunohistochemical (IHC) expression of five potential biomarkers/prognostic markers in high grade epithelial ovarian carcinoma: EGFR, HLA-G, CD70, c-MET, and NY-ESO1. A cohort of 274 patients is used. We compare the IHC expression with age, stage, ascites status, family history of cancer, disease free survival (DFS) and overall survival (OS). EGFR expression is significantly correlated with family history and worse OS. HLA-G is associated with worse OS. To confirm the results of EGFR and HLA-G, a second separated cohort of 248 patients is used. Positive EGFR expression again shows worse OS, while HLA-G expression has worse prognostic trend. CD70 has a worse OS trend. C-MET and NY-ESO1 do not have any clinical correlations. EGFR can potentially serve as target in future clinical immune therapy trials.

Small Cell Lung Cancer in Norway: Patterns of Care by Health Region and Survival Trends

Introduction/BackgroundThere has been a marked survival improvement for patients with non–small-cell lung cancer. We describe the national trends in characteristics and survival, and geographical differences in diagnostic workup, treatment, and survival for patients with small-cell lung cancer (SCLC). Materials and MethodsPatients registered with SCLC at the Cancer Registry of Norway in 2002 to 2022 were included. Trends in overall survival were estimated for all SCLC patients, patients with limited stage SCLC, patients undergoing surgery, and by health region. Adjusting for case-mix, a multivariable Cox regression was performed examining the association between health region and death. ResultsThe study included 8374 patients. The stage distribution remained unchanged during the study period. The 5-year overall survival increased from 7.7% to 22.8% for patients with limited stage. The use of multidisciplinary team meetings varied from 62.5% to 85.7%, and the use of positron emission tomography-computer tomography varied from 70.4% to 86.2% between the health regions. Treatment patterns differed markedly between the health regions, with the proportion dying without any registered treatment ranging from 1.2% to 10.9%. For limited stage patients in 2018 to 2022, the median overall survival ranged from 16.5 to 25.5 months across health regions, and the 5-year overall survival ranged from 18.7% to 28.7% (P = .019). ConclusionThe survival for patients with SCLC remains poor. The use of diagnostic procedures, treatment modalities, and survival differed between regions, warranting investigations to further explore the reasons.

Upregulation of the Renin-Angiotensin System Is Associated with Patient Survival and the Tumour Microenvironment in Glioblastoma.

Glioblastoma is a highly aggressive disease with poor survival outcomes. An emerging body of literature links the role of the renin-angiotensin system (RAS), well-known for its function in the cardiovascular system, to the progression of cancers. We studied the expression of RAS-related genes (ATP6AP2, AGTR1, AGTR2, ACE, AGT, and REN) in The Cancer Genome Atlas (TCGA) glioblastoma cohort, their relationship to patient survival, and association with tumour microenvironment pathways. The expression of RAS genes was then examined in 12 patient-derived glioblastoma cell lines treated with chemoradiation. In cases of glioblastoma within the TCGA, ATP6AP2, AGTR1, ACE, and AGT had consistent expressions across samples, while AGTR2 and REN were lowly expressed. High expression of AGTR1 was independently associated with lower progression-free survival (PFS) (p = 0.01) and had a non-significant trend for overall survival (OS) after multivariate analysis (p = 0.095). The combined expression of RAS receptors (ATP6AP2, AGTR1, and AGTR2) was positively associated with gene pathways involved in hypoxia, microvasculature, stem cell plasticity, and the molecular characterisation of glioblastoma subtypes. In patient-derived glioblastoma cell lines, ATP6AP2 and AGTR1 were upregulated after chemoradiotherapy and correlated with an increase in HIF1A expression. This data suggests the RAS is correlated with changes in the tumour microenvironment and associated with glioblastoma survival outcomes.

Abstract CT239: IMpower010: Updated overall survival and safety results from Asian patients in a Phase III study of adjuvant atezolizumab vs best supportive care in resected stage IB-IIIA NSCLC

Abstract Background The Phase III IMpower010 study (NCT02486718) met its primary endpoint at the disease-free survival (DFS) interim analysis (IA; clinical cutoff: Jan 21, 2021), demonstrating significant DFS improvement with atezolizumab (atezo) vs best supportive care (BSC) after adjuvant chemotherapy (chemo) in patients with resected stage II-IIIA NSCLC, including those with PD-L1 TC ≥1%. Based on these findings, atezo was approved as adjuvant therapy after platinum-based chemo in patients with completely resected PD-L1 TC ≥1% stage II-IIIA NSCLC in the US, China and other countries, and in patients with completely resected PD-L1 TC ≥50% stage II-IIIA NSCLC in the EU and other countries. In a previous exploratory analysis at the time of the DFS IA, the IMpower010 Asian subpopulation showed efficacy and safety outcomes that were consistent with those of the global population (Kenmotsu et al. JSMO 2021). Here we report updated data from the IMpower010 Asian subpopulation at the first overall survival (OS) IA. Methods The IMpower010 study design and DFS IA have been previously reported (Felip et al. Lancet 2021). Eligible patients with completely resected stage IB (≥4 cm)-IIIA NSCLC (AJCC/UICC v7) received one to four 21-day cycles of cisplatin-based doublet chemo and were subsequently randomized 1:1 to receive atezo 1200 mg q3w (16 cycles) or BSC. The first pre-specified OS IA was conducted at the clinical cutoff date of Apr 18, 2022. OS in the intention-to-treat (ITT) population will be formally tested if DFS in the ITT population reaches statistical significance at the final DFS analysis. Exploratory OS and updated safety outcomes were evaluated in the Asian subpopulation. Results The Asian ITT population included 233 patients recruited from Japan, mainland China, Taiwan, Korea and Hong Kong. At data cutoff (Apr 18, 2022), the unstratified OS HR was 0.73 (95% CI: 0.28, 1.88) in favor of atezo in the PD-L1 TC ≥1% (SP263) stage II-IIIA population (n=129). The Asian safety-evaluable population included 229 patients (atezo, n=122; BSC, n=107). Any-grade adverse events (AEs) were reported in 95.1% (atezo) and 72.0% (BSC) of safety-evaluable patients; events were Grade 3/4 in 24.6% and 13.1%, respectively. Grade 5 treatment-related AEs occurred in 1 patient in the atezo arm. AEs leading to atezo discontinuation occurred in 21.3% of patients treated with atezo. Conclusions The IMpower010 Asian subpopulation showed an OS trend favoring atezo vs BSC in the PD-L1 TC ≥1% stage II-IIIA population, as was observed in the global population, although OS data were not formally tested in either population at the first OS IA. With longer follow-up, the safety findings for atezo in the IMpower010 Asian subpopulation remained broadly unchanged, were consistent with those of the global IMpower010 population and were in line with the known safety profile of atezo. Medical writing support for this abstract was provided by Kia C. E. Walcott, PhD, of Nucleus Global, an Inizio Company, and funded by F. Hoffmann-La Roche, Ltd. Citation Format: Jie Wang, Yun Fan, Jian Fang, Jianxing He, Yunpeng Liu, Min Tao, Nasser Altorki, Enriqueta Felip, Heather Wakelee, Eric Vallieres, Rossella Belleli, Virginia McNally, Elizabeth Bennett, Barbara J. Gitlitz, Caicun Zhou. IMpower010: Updated overall survival and safety results from Asian patients in a Phase III study of adjuvant atezolizumab vs best supportive care in resected stage IB-IIIA NSCLC [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr CT239.

Second Line Therapy in Multiple Myeloma: A SEER Medicare Analysis

IntroductionThe therapeutic landscape in relapsed/refractory multiple myeloma (RRMM) has changed rapidly, with twenty-two drug approvals since 2012. We characterized population-level trends in RRMM therapy selection, survival and cost outcomes associated with RRMM treatment over time. Materials and MethodsOur cohort included adults diagnosed with multiple myeloma (MM) in the SEER-Medicare database from 2007-2017 who received at least one antimyeloma agent. MM-directed therapies and lines of therapy were identified. Changes in 2LT regimens over time were described. Trends in overall survival from 2LT initiation over time were analyzed using a Cox proportional hazards model adjusting for factors associated with survival in MM. Trends in mean inflation-adjusted cost per 12 months of 2LT were analyzed using JoinPoint analysis. ResultsA total of 9,822 patients met eligibility criteria, of whom 5,866 (59.7%) received 2LT. By 2018, 46% of 2LT regimens contained at least one agent approved in 2012 or later. Year of 2LT initiation was associated with improved overall survival (HR 0.78 per 5 years, 95% CI 0.74-0.84) after adjustment. Costs associated with 2LT increased over the study period, and the rate of cost increase increased significantly after 2012 (0.89%/year vs. 9.9%/year, P < .001), with higher total costs for regimens containing newer novel agents (mean $224,193 vs. $189,381, P < .001) ConclusionOverall survival after initiation of 2LT has improved, however this has been accompanied by significant increases in costs of RRMM treatment, particularly for patients receiving newer novel agents. These findings provide useful context for existing and future drug approvals in RRMM.

Value of surgery combined chemotherapy and radiation therapy in locally advanced neuroendocrine carcinoma of the cervix: a single-center retrospective cohort study

Objective: To evaluate the surgery combined chemotherapy and radiation in locally advanced neuroendocrine carcinoma of the cervix (NECC) . Methods: This is a single-center retrospective cohort study. Locally advanced NECC patients admitted to Peking Union Medical College Hospital, Chinese Acadmy of Medical Sciences from January 2011 to April 2022 were enrolled. They were divided into concurrent chemoradiotherapy group, and surgery combined with chemotherapy and radiation group. The Kaplan-Meier method was used to analyze the progression free survival (PFS), overall survival (OS), recurrence rate, and mortality rate. Results: (1) Forty-six cases were included, 22 in concurrent chemoradiotherapy group, 24 in surgery combined chemotherapy and radiation group. With 16 patients (35%, 16/46) received neoadjuvant chemotherapy (NACT), the NACT effective rate was 15/16. (2) The median follow-up time was 27.5 months (range: 10-106 months), with 26 (57%, 26/46) experienced recurrences. There were 4 (9%, 4/46) pelvic recurrences and 25 (54%, 25/46) distant recurrences, and 3 (7%, 3/46) both pelvic and distant recurrences. Compared with concurrent chemoradiotherapy group, surgery combined chemotherapy and radiation group had lower pelvic recurrence rate [14% (3/22) vs 4% (1/24); χ2=1.296, P=0.255] but without statistic difference. Both groups had similar distant recurrence rate [55% (12/22) vs 54% (13/24); χ2=0.001, P=0.979] and overall recurrence rate [59% (13/22) vs 54% (13/24); χ2=0.113, P=0.736]. (3) During the follow-up period, 22 cases (48%, 22/46) died, with 11 cases (50%, 11/22) in concurrent chemoradiotherapy group and 11 cases (46%, 11/24) in surgery combined chemotherapy and radiation group, without significant difference (χ2=0.080, P=0.777). The postoperative 3-year and 5-year OS rates were 62.3% and 36.9%. Compared with concurrent chemoradiotherapy group, the patients in surgery combined chemotherapy and radiation group showed an extended trend in PFS (17.0 vs 32.0 months) and OS (37.0 vs 50.0 months) but without statistic differences (P=0.287, P=0.125). Both groups had similar 3-year OS rate (54.2% vs 69.9%; P=0.138) and 5-year OS rate (36.1% vs 38.8%; P=0.217). Conclusions: Our study supports the multi-modality treatment strategy (including surgery, chemotherapy and radiation) as an important component in the treatment of locally advanced NECC. The combination of surgery, chemotherapy and radiation seems to have advantages in the treatment of locally advanced NECC, but needs to be confirmed by further multicenter studies.

Abstract 4871: Colorectal cancer incidence and overall survival by race, stage, and age: A SEER database analysis, 2009-2020

Abstract Introduction: In the United States, colorectal cancer (CRC) is the fourth most common cancer and the second leading cause of cancer-related deaths. Although incidence rates of CRC have been decreasing overall, recent studies suggest a shift in demographics, specifically an increase in the number of new CRC cases among younger individuals and a higher incidence among those who identify as non-Hispanic Native American/Alaska Native. To examine the latest trends in incidence and overall survival (OS) among adults with CRC in the United States, we conducted an observational study using the Surveillance, Epidemiology, and End Results (SEER) Program database. Methods: Patients aged ≥18 years with newly diagnosed CRC between January 1, 2009, and December 31, 2020 were identified in the SEER 17 database. Age-adjusted incidence rates for CRC were calculated by race/ethnicity and age groups (18-49, 50-64, and ≥65 years) from 2009 to 2020. Kaplan-Meier curves were generated to examine 5-year OS by race/ethnicity, stage, and age groups. Results: There were 429,218 CRC cases identified with a median age of 67 years. Most were male (52.4%) with stage 0-II CRC (51.4%). Most patients identified as non-Hispanic White (66.3%), followed by non-Hispanic Black (11.5%), non-Hispanic Asian/Pacific Islander (8.9%), non-Hispanic Native American/Alaska Native (0.7%), and Hispanic of any race (12.7%). The age-adjusted incidence rate between 2009 and 2020 was 51.9 per 100,000 persons; incidence decreased from 59.5 per 100,000 persons in 2009 to 44.2 per 100,000 persons in 2020, with male patients having a higher incidence rate than female patients. By 2020, non-Hispanic Native American/Alaska Native patients had the highest incidence rate (54.5 per 100,000 persons) followed by non-Hispanic Black patients (50.6 per 100,000 persons). CRC incidence rates increased slightly for age &amp;lt;50 years (10.5 to 12.9 per 100,000 persons) and decreased for ages 50-64 (74.6 to 63.9 per 100,000 persons) and ≥65 years (222.4 to 136.1 per 100,000 persons). Non-Hispanic Black patients (53%), age ≥65 years (47%), and those with stage III-IV CRC (41%) had a lower 5-year OS from 2015 to 2019 compared to patients who were non-Hispanic White (57%), aged 50-64 (68%) and &amp;lt;50 years (70%), and with stage 0-II CRC (77%). Conclusion: Our results confirm a slight increase in CRC incidence among younger (&amp;lt;50 years) individuals over the 2009-2020 time period. Patients who were non-Hispanic Native American/Alaska Native had the highest CRC incidence rate and patients who were non-Hispanic Black had the poorest OS. Targeted preventative efforts such as CRC screening programs in addition to improved access to care/treatment may be needed to reduce the number of new cases and improve outcomes among historically underserved groups. Citation Format: Alicia C. McDonald, Seongjung Joo, Jiemin Ma, Mayur M. Amonkar, Changxia Shao, Kaushal Desai, Anne C. Deitz. Colorectal cancer incidence and overall survival by race, stage, and age: A SEER database analysis, 2009-2020 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4871.

Abstract 7650: An analysis of the prognostic role of sarcopenia derived with fully automated deep learning slice-based muscle estimation in patients with metastatic non-small cell lung cancer (NSCLC)

Abstract Introduction: Sarcopenia, progressive and generalized loss of skeletal muscle mass, is difficult and labor intensive to directly measure as it requires manual segmentations by radiologists from computed tomography (CT) scans. Sarcopenia has been shown to be a prognostic factor in some metastatic cancers. We evaluated the impact of sarcopenia derived via an automated segmentation algorithm on outcomes in the Phase 3 NSCLC clinical trial, CheckMate 227 (NCT02477826) Methods: The sarcopenia score assessment involves automated selection of the L3 vertebra level slice from abdominal or chest, abdomen, and pelvis (CAP) CT scans, followed by automated segmentation of the muscle area from that slice. Sarcopenia scores were derived from previously established definitions of sarcopenia, with values below 41 cm2/m2 for female patients (regardless of BMI) and below 43 cm2/m2 or 53 cm2/m2 for male (based on BMI &amp;lt; 25 kg/m2 or ≥ 25 kg/m2). Among the 967 patients with evaluable scans, sarcopenia at baseline was identified in 68.39% (n=329/481) patients receiving nivolumab (NIVO) with ipilimumab (IPI) and 70.2% (n=341/486) receiving chemotherapy (Chemo). Results: There was a trend of worse overall survival (OS) in patients with baseline sarcopenia across both treatment arms (minimum follow up 49.4 months). In patients with baseline sarcopenia vs ITT, median OS was 16.5 mo vs. 21.8 mo (p= 0.219) within the NIVO + IPI arm and 12.9 mo vs.15.0 mo (p= 0.273) within the Chemo arm respectively. Any increase in muscle mass from baseline to week 12 was associated with better OS for patients treated with NIVO+IPI (n=98) with sarcopenia at baseline compared to those without an increase in muscle mass (median OS 45.3 mo vs.19.5 mo, p= 0.012). This was not seen in those who received Chemo (n=87). Weight and muscle mass were moderately correlated at baseline (r=0.60). Conclusions: We found that in CheckMate 227, baseline sarcopenia is associated with numerically worse OS, regardless of treatment, leading to potential use as a negative prognostic biomarker. Patients with NSCLC receiving immunotherapy might benefit from changes in muscle mass being monitored during treatment. Validation of these findings in other studies and other tumor types is warranted. Citation Format: Wiem Safta, Rafael Santana-Davila, David Paulucci, William J. Geese, Diederik J. Grootendorst. An analysis of the prognostic role of sarcopenia derived with fully automated deep learning slice-based muscle estimation in patients with metastatic non-small cell lung cancer (NSCLC) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 7650.

Survival in Patients With De Novo Metastatic Prostate Cancer

This cross-sectional study investigates trends in overall survival among patients with newly diagnosed metastatic prostate cancer in 2 national registries in the United States.

Sequential multimodal treatments with chemotherapy and surgery for advanced soft tissue sarcoma may be associated with better survival than chemotherapy

BackgroundIn patients with advanced soft tissue sarcoma (STS), surgery had been reported to be associated with superior overall survival (OS). Chemotherapy details for such patients were less reported, and whether multimodal treatment with surgery and chemotherapy provides extra survival benefit remains unclear. MethodsWe retrospectively reviewed patients with newly diagnosed advanced STS treated at National Taiwan University Hospital from January 1, 2011, to December 31, 2017. OS was calculated from the day of diagnosis of advanced STS to the day of death or last follow-up. Baseline patient characteristics and details regarding surgery and chemotherapy were recorded. ResultsA total of 545 patients were diagnosed with STS from 2011 to 2017, of which 226 patients had advanced STS. The median age was 54.7 years, and 54% of patients were women. Approximately 38% of patients with advanced STS underwent surgery and exhibited a trend of longer OS compared with who did not (median = 18.6 vs. 11.9 months, p = 0.083). In the chemotherapy subgroup, the benefit of surgery was more prominent (median = 21.9 vs. 16.5 months, p = 0.037). Patients who received chemotherapy prior to surgery exhibited numerically longer OS than those who underwent surgery first (median = 33.9 vs. 18.3 months, p = 0.155). After adjusting other clinical factors, chemotherapy remained an independent factor associated with favourable OS. ConclusionSurgery may be more beneficial for the patients who receive chemotherapy. Our results support evaluation of sequential multimodal treatments strategy including surgery and chemotherapy in patients with advanced STS.