Median On Overall Survival For Patients Research Articles

Potentially inappropriate medications, their adverse events, and impact on geriatric vulnerabilities, frailty, and survival in older Indian patients with cancer: A retrospective observational study

Background: Older adults often have chronic diseases for which they receive multiple drugs, which may be potentially inappropriate. Objectives: We aimed to describe the potentially inappropriate medications (PIMs) leading to adverse drug events (ADEs) in older patients with cancer. Our secondary objectives were to evaluate the association of nutrition, cognition, and frailty with PIM-related ADEs and to assess the impact of PIM-related ADEs on overall survival (OS). We also investigated the cut-off for defining polypharmacy as related to ADEs. Materials and Methods: This was a retrospective observational study on patients with cancer aged 60 years and over who were assessed in the geriatric oncology clinic at the Tata Memorial Hospital (Mumbai, India) from June 2018 to August 2022. Medications, PIM assessment, nutrition (assessed by Mini Nutritional Assessment [MNA]), cognition (assessed by Mini Mental State Examination [MMSE] and Hindi Mental State Examination), and frailty (assessed by the Clinical Frailty Scale [CFS]) were extracted from the geriatric oncology clinic database. PIMs were identified using the Beers criteria, European Union-7 (EU[7])-PIM, Screening Tool of Older person’s Prescriptions/Screening tool to Alert to Right Treatment (STOPP/START), Fit fOR The Aged (FORTA), and PRISCUS list. Results: In total, 1472 patients were assessed in the geriatric oncology clinic, of which 823 (55.9%) were enrolled in the study. There were 1287 PIMs detected in 823 patients, of which 431 (33.5%) led to ADEs and 856 (66.5%) did not. Proton pump inhibitors and tramadol were the most common PIMs identified. ADEs were noted in 54 (14.7%) patients on proton pump inhibitors and in 145 (61.1%) patients on tramadol. ADEs were significantly associated with malnutrition, lower cognition, and frailty. The median MNA score in patients without and with ADEs was 20.5 (interquartile range [IQR], 17.5-24.0) and 19.5 (IQR, 15.5–23.5), respectively; P, 0.001. The median MMSE score for the patients without and with ADEs was 28 (IQR, 26-29) and 27 (IQR: 25-29), respectively; P, 0.001. The median CFS scores for the patients without and with ADEs were 3 (IQR, 2-4) and 4 (IQR, 3-5), respectively; P < 0.001. The median OS in patients without and with ADEs was 13.1 months (95% confidence interval [CI], 10.64-17.87) and 10.2 months (95% CI, 8.80-12.85), respectively; P, 0.002. The optimal cut-off for polypharmacy leading to ADEs was 4.5 medications. Conclusions: There is a dire need to recognize and appropriately manage PIMs in older patients with cancer as PIM-related toxicities may negatively impact survival. Monitoring PIMs and following the recommendations to optimize the dose, avoid the drug, and find alternatives may improve the oncologic outcomes. Future studies should focus on adding a control group of patients not on PIMs, following up on PIM after recommendations, and investigating the impact of these recommendations on oncologic outcomes (Clinical Trials Registry-India: CTRI/2020/04/024675).

DNA Mutational Profiling in Patients With Colorectal Cancer Treated With Standard of Care Reveals Differences in Outcome and Racial Distribution of Mutations.

CALGB (Alliance)/SWOG 80405 was a randomized phase III trial that in first-line patients with metastatic colorectal cancer (mCRC) treated with bevacizumab or cetuximab with chemotherapy. We aimed to discover novel mutated genes associated with prognosis and differential response to therapy with the biologics. Primary tumor DNA from 548 patients was sequenced using FoundationOne. The effect of mutated genes and mutations on overall survival (OS) was tested adjusting for microsatellite instability status, BRAF V600E, all RAS mutations, arm, sex, and age. The median number (lower-upper quartile) of mutated genes was 5 (3-7), 5 (3-6) in microsatellite stable and 12.5 (4.5-32) in microsatellite instability-high tumors. Mutated KRAS and APC were more frequent in Black (53% and 85%) than White (27% and 65%, respectively) patients while BRAF V600E was less frequent in Black (5%) than White (14%) patients. The median OS in patients with BRAF non-V600E (2.2% of patients) was 31.9 months (95% CI, 15.1 to not applicable [NA]) similar to that of BRAF wild-type (WT) patients (31.2 months [95% CI, 29.0 to 33.9]). Mutated LRP1B (10.7% of patients) was associated with improved OS compared with WT LRP1B (hazard ratio, 0.57 [95% CI, 0.40 to 0.80]). RNF43 (5.6% of patients) interacted with treatment arms as, in the cetuximab arm, patients with mutated RNF43 had a median OS of 11.5 (95% CI, 10.8 to NA) months compared with 30.1 (95% CI, 24.9 to 35.3) months in patients with WT RNF43, whereas in the bevacizumab arm, patients with mutated RNF43 had a median OS of 25.0 (95% CI, 14.2 to NA) months compared with 31.3 (95% CI, 29.0 to 34.3) months in patients with WT RNF43. These results can provide new tools to predict patient outcome and improve therapeutic decisions and trial participation in patient minorities. The molecular alterations identified in this study may direct biomarker-driven studies.

Risks and benefits of phase 1 clinical trials for patients with relapsed or refractory lymphoma, from 2008 to 2023

Introduction: Previous reviews of phase 1 trials in oncology have reported a treatment response rate of 4%–6% and a toxicity-related mortality rate of 0.5%. These results may not reflect current Phase 1 trial rates for patients with lymphoma. Methods: All non-pediatric phase 1 trials for relapsed or refractory (R/R) lymphoma approved by the Cancer Therapy Evaluation Program of the Institut Gustave Roussy between 2008 and 2023 (cut-off date 05 January 2023) were reviewed. We reported on overall survival (OS), treatment response rates, treatment-related deaths, and the number of patients who benefit to have received a drug in clinical trial which was further approved by the health authorities (FDA or EMA). Results: We analyzed 50 trials involving 447 participants (pts) with R/R lymphoma who received at least one dose of treatment. All patients were assessed for toxicity and 382/447 (85%) for treatment response. The median (range) age of patients was 64.9 (19.2–88.5) years. The median of treatments received before entering the trial was 3 (1–13). The main types of lymphoma were DLBCL (n = 253; 56.6%), PTCL (n = 45; 10.1%), Hodgkin (n = 40; 8.9%) and FL (n = 39; 8.7%). The overall response rate (i.e complete and partial responses) was 23.6%. Drug classes in trials included epigenetic modifiers (n = 99 pts; 22.1%), Proteolysis Targeting Chimeras (PROTAC) (n = 90; 20.1%), IO (n = 77; 17.2%), anti-apoptotic inhibitor (n = 50; 11.2%), molecular targeted therapy (n = 46; 10.3%), T-Cell Engagers (n = 23; 5.1%), antibody drug conjugated (n = 20; 4.5%), monoclonal antibody (n = 17; 3.8%), cycle cellular inhibitor (n = 8; 1.8%), gamma secretase inhibitor (n = 8; 1.8%), chemotherapy (n = 5; 1.1%), antiangiogenic (n = 4; 0.9%). Trials including drug further approved by health authorities involved 84/447 (18.8%) of patients and had an overall response rate of 32.9% (26/79 evaluable pts). The overall rate of deaths due to toxic events was 0.45% (2/447 pts). The median OS of patients was 14.1 (CI95% 11.7–17.9) months, with significant variation among lymphoma types (p < 0.0001) (Figure 1). Poor OS was observed for patients with relapsed or refractory with peripheral T-cell lymphoma (8.9 months CI95% 6.9–9.6) (Figure 1). Overall survival of patients with relapsed or refractory lymphoma included in phase 1 trials from 2008 to 2023, according to the lymphoma type (CLL = Chronic lymphoid leukemia; DLBCL = Diffuse large B cell lymphoma; FL = Follicular lymphoma; MCL = Mantle cell lymphoma; MZL = Marginal zone lymphoma; WD = Waldenstrom disease; PTCL = Peripheral T cell lymphoma). Conclusion: Overall response rates among phase 1 trials for patients with R/R lymphoma are higher than those reported with phase 1 in oncology. Toxicity-related mortality rates are similar those reported with phase 1 in oncology. The research was funded by: Ideogen (funding for clinical data analysis) Keywords: Aggressive B-cell non-Hodgkin lymphoma, Aggressive T-cell non-Hodgkin lymphoma, Indolent non-Hodgkin lymphoma Conflicts of interests pertinent to the abstract. J. M. Michot Honoraria: Ideogen (clinical data analysis)

Immunotherapy-related adverse events in real-world patients with advanced non-small cell lung cancer on chemoimmunotherapy: a Spinnaker study sub-analysis.

The Spinnaker study evaluated survival outcomes and prognostic factors in patients with advanced non-small-cell lung cancer receiving first-line chemoimmunotherapy in the real world. This sub-analysis assessed the immunotherapy-related adverse effects (irAEs) seen in this cohort, their impact on overall survival (OS) and progression-free survival (PFS), and related clinical factors. The Spinnaker study was a retrospective multicentre observational cohort study of patients treated with first-line pembrolizumab plus platinum-based chemotherapy in six United Kingdom and one Swiss oncology centres. Data were collected on patient characteristics, survival outcomes, frequency and severity of irAEs, and peripheral immune-inflammatory blood markers, including the neutrophil-to-lymphocyte ratio (NLR) and systemic immune-inflammation index (SII). A total of 308 patients were included; 132 (43%) experienced any grade irAE, 100 (32%) Grade 1-2, and 49 (16%) Grade 3-4 irAEs. The median OS in patients with any grade irAES was significantly longer (17.5 months [95% CI, 13.4-21.6 months]) than those without (10.1 months [95% CI, 8.3-12.0 months]) (p<0.001), either if Grade 1-2 (p=0.003) or Grade 3-4 irAEs (p=0.042). The median PFS in patients with any grade irAEs was significantly longer (10.1 months [95% CI, 9.0-11.2 months]) than those without (6.1 months [95% CI, 5.2-7.1 months]) (p<0.001), either if Grade 1-2 (p=0.011) or Grade 3-4 irAEs (p=0.036). A higher rate of irAEs of any grade and specifically Grade 1-2 irAEs correlated with NLR <4 (p=0.013 and p=0.018), SII <1,440 (p=0.029 ad p=0.039), response to treatment (p=0.001 and p=0.034), a higher rate of treatment discontinuation (p<0.00001 and p=0.041), and the NHS-Lung prognostic classes (p=0.002 and p=0.008). These results confirm survival outcome benefits in patients with irAEs and suggest a higher likelihood of Grade 1-2 irAEs in patients with lower NLR or SII values or according to the NHS-Lung score.

Effect of ABO Mismatch and RBC Alloimmunization on the Outcomes of Patients with Sickle Cell Disease Undergoing Hematopoietic Stem Cell Transplantation

Background: Hematopoietic stem cell transplantation (HSCT) remains the only well-established curative option for sickle cell disease (SCD) patients. Non-myeloablative (NMA) conditioning has been used to improve the outcomes and reduce toxicities in adult SCD patients. However, Recipient/Donor (R/D) ABO incompatibility and alloimmunization could be significant impediments to successful outcomes when transplanting SCD patients due to risks of hemolysis, delayed engraftment, poor graft function and graft failure (GF). Herein, we report our experience with allogeneic HSCT for SCD and the effects of RBC groups mismatch and alloimmunization on the outcome of transplanted patients. Methods: We conducted a retrospective analysis of all adolescents and adult SCD patients (age >14 year) that underwent HSCT from January 2015 to February 2022 at our center. All patients received Intravenous alemtuzumab (1 mg/kg divided over 5 days on days -7 to -3) and 300 cGy TBI on day -2 or -1 for conditioning. Pre-transplant preparation consisted of hydroxyurea at maximum tolerated dose for 2-3 months and one session of exchange transfusion. Peripherally mobilized stem cells targeting 10x106 /kg of CD34 cells were used. For graft versus host disease (GVHD) prophylaxis sirolimus was started on day -1 and continued for one year with tapering if lymphoid chimerism was > 50%. For Patients with major ABO incompatibility, we administered 2 doses of rituximab (375 mg/m2) and 3 sessions of plasmapheresis before starting the conditioning regimen targeting an isoheamagglutinin titer < 1/32. The primary objective was to determine the impact of RBC groups mismatch and alloimmunization on the outcome of transplanted patients. The secondary objective was to assess the impact of GF on overall survival (OS). Logistic regression was done to evaluate predictors for GF. Kaplan-Meier method was used for survival analysis. Results: A total of 194 patients were included with a median age of 26 years and 55.6% being males. The median baseline Hgb and HbS were 93 g/L and 71.3%, respectively. Indications of stem cell transplantations were most commonly due to recurrent vaso-occlusive crisis in 52.57% of patients, CNS disease in 19.58%, and acute chest syndrome in 17.01%. Other indications included sickle nephropathy, sickle hepatopathy, priapism and AVN in 10.82% of patients collectively. Around 59% of donors were sickle cell disease carriers, and 41% were healthy donors. After a median follow up of 28.8 months (5-83), sixteen patients (8%) experienced graft failure (3 with primary GF and 13 with secondary GF). On univariate analysis (table 1a), ABO minor incompatibility (odds ratio (OR), 3.63; 95% confidence interval (CI), 1.13 -11.65, P=0.029, and RBC alloantibodies against donor non-ABO antigens (OR, 4.22; 95% CI, 1.17 -15.14, P=0.039) were predictive for GF. However, on multivariate analysis (table 2a), only RBC alloantibodies against donor non-ABO antigens (OR, 8.29; 95% CI, 2.01 to 34.05, P=0.0033) was predictive of GF. None of the 16 patients with major ABO incompatibility developed GF. Two-years OS for all patients was 95%. The median OS for patients with GF was 98% compared to 74% patients without GF, P<0.0001) (Figure 1). Conclusion: In our SCD transplanted patients, RBC alloantibodies against donor non-ABO antigens was an independent risk factor for GF. Patients with GF had an inferior survival and strategies for decreasing the risks are needed. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Impact of Comorbidity Scores on the Overall Survival of Patients With Advanced Non-small Cell Lung Cancer: A Real-World Experience From Eastern India.

Introduction Lung cancer is the most common cancer, and it is the leading cause of cancer-related death. Smoking is the most common risk factor for the development of lung cancer. There is a lack of data on the comorbidities and outcomes of advanced non-small cell lung cancer (NSCLC) in the eastern part of India. This prospective study evaluated the impact of comorbidity scores on overall survival (OS) in these patients. Method This prospective cohort study was conducted on newly diagnosed advanced NSCLC patients between June 2020 and April 2021. These patients were given platinum-based doublet chemotherapy guided by histology and targeted therapy based on molecular studies. Comorbidities were assessed using the Charlson Comorbidity Index (CCI), Simplified Comorbidity Score (SCS), and Adult Comorbidity Evaluation-27 (ACE-27). The outcome assessed was OS. Overall survival was calculated in days from the date of start of anticancer therapy to the date of last follow-up or date of death. All enrolled patients were followed at regular intervals whenever they visited the hospital and telephonically until April 2022. The patients who were alive on April 30, 2022, were censored. The survival probability and median OSwere calculated by Kaplan-Meier analysis, and group differences in comorbidity scores were analyzed with the log-rank test. A Cox proportional hazard analysis was performed to look for factors affecting overall survival. Results A total of 114 patients were enrolled in the study period, and the mean age of patients was 56.54 ± 11.03 years. Most of the patients were males (68.4%), and 52.6% were smokers. Adenocarcinoma was the most common histology (73.7%), followed by squamous cell carcinoma (25.4%). The median OS was 127 days (95% CI, 60-193 days). 33.4% of the patients had a CCI score of 0, a CCI score of 1 was seen in 57%, and ≥2 scores in 9.6%. SCS scores ≤9 and >9 were seen in 92.1% and 7.9% of patients, respectively. The ACE-27 score was none in 41 subjects, mild in 59, moderate in 12, and 2 NSCLC subjects had severe ACE-27 scores. The median OS for patients with a CCI score of 0 was 275 days (95% CI, 7-543 days), 114 days (95% CI, 85-142 days) for subjects with a CCI score of 1, and 402 days (95% CI, 0-844 days) for patients with a CCI score ≥2 (log-rank p = 0.215). Individuals with an SCS score ≤9 had a median OS of 175 days (95% CI, 91-258 days), and the median OS was 92 days (95% CI, 80-103 days) for patients with an SCS score >9 (log-rank p = 0.302). Median OS of the patients with ACE-27 score 0,1,2,3 were 297 days (95% CI, 76- 517 days), 117 days (95% CI, 81-152 days), 87 days (95% CI, 49-124 days) and 66 days, respectively (log-rank p=0.457). There was no statistical significance between comorbidity scores and OS. Worse OS was independently associated with poor performance status Eastern Cooperative Oncology Group (ECOG) ≥2 (hazard ratio [HR]3.266; 95% CI 1.785-5.978; p = 0.00), neutrophil-to-lymphocyte ratio (NLR) <3 (HR, 2.35 95% CI 1.18-4.702; p = 0.015) and patients who were given compassionate tyrosine kinase inhibitors (TKIs) (HR, 7.396 95% CI 3.531-15.490; p = 0.000). Conclusions In our study, the advanced NSCLC patients who were given chemotherapy or oral TKIs showed no significant influence of comorbidities on overall survival. Factors independently associated with the worst survival were poor performance status (ECOG ≥ 2), NLR < 3, and patients who were given TKIs on a compassionate basis.

Time to first treatment is an independent prognostic factor for Multiple Myeloma (MM)

IntroductionMultiple myeloma (MM) is an incurable plasma cell neoplasm. In this study, we aimed to analyze the impact of time to initiation of systemic therapy for MM on overall survival (OS). MethodsWe identified cases diagnosed with MM from the National Cancer Database from 2004 to 2013. ResultsA total of 38,178 MM patients were included in the analysis. The median time to systemic therapy in our cohort was 17 days (range 0–120). The median OS for patients who initiated therapy > 30-days after diagnosis was longer than those who received it ≤ 7 days (46 vs. 27-month, p < 0.001). On multivariable analysis, patients who received treatment ≤ 7 days from diagnosis had worse mortality compared with those receiving treatment > 30 days (HR 1.5; 95% CI 1.4–1.6). ConclusionsIn our study, time to initiation of systemic therapy was an independent prognostic factor in MM. Similar to other lymphoid malignancies, this metric may be a surrogate for high-risk disease in MM, and future trials may need to investigate time-to-treatment as a factor to allow enrollment of potentially sick patients.

Comparative analysis of overall survival in non-small cell lung cancer patients with and without different organ metastases

Lung cancer is the leading cause of cancer death globally. Non-small cell lung cancer (NSCLC) constitutes more than 80% of all lung cancers, and patients with distant metastasis have much higher mortality. The survival times of NSCLC patients with metastasis have been reported in early studies, however, it remains unclear whether there are variations or patterns in survival times of patients with different metastases. Therefore, we assessed risk factors for distant metastases and the effects of different organ metastasis on overall survival (OS) in patients with NSCLC. Methods: demographics and clinical data of NSCLC patients with and without distant metastasis were collected from the Surveillance, Epidemiology, and End Result (SEER) database between 2010 and 2016. We investigated risk factors for distant metastasis patients and compared the difference in OS of NSCLC patients with different metastatic sites. Results: a total of 3849 patients diagnosed with NSCLC were screened from the SEER database with 41% (1577) of the patients having distant metastasis. During the follow-up period, 3221 (83.7%) patients died and, of all the deceased patients, 2935 (88.4%) died of lung cancer while only 286 (11.6%) died from other diseases or causes. The occurrence of distant metastasis was closely related to the patient’s age, primary tumour site, tumour grade, T stage, N stage, surgery of primary site, radiation therapy, and chemotherapy (p&lt;0.05). Compared to patients without metastasis, whose median OS was 13 months, the median OS of patients with metastasis was 6 months (lung), 5 months (liver), 5 months (bone), 4 months (brain), and 3 months (multiple organs). Conclusions: distant metastasis indicates a poor prognosis in NSCLC patients. There were significant differences in the prognosis of different metastatic sites and the order of their OS from high to low was: no metastasis &gt; lung metastasis, liver metastasis, bone metastasis &gt; brain metastasis, multiple organ metastasis.

Rheumatic and musculoskeletal disorders induced by immune checkpoint inhibitors: Consequences on overall survival.

Immune checkpoint inhibitors (ICIs) frequently induce immune related adverse events (irAEs) that may be associated with more favorable clinical outcomes. We aimed to evaluate the impact of all types of rheumatic adverse events (AEs) on overall survival (OS) and tumor response in patients treated with ICIs. We performed a single-center retrospective observational study to analyze the OS and tumor response in patients receiving ICIs who experienced a rheumatic AE compared to those who did not experience any AE. From December 2010 to September 2018, 264 patients with any cancer type were included. Forty-three patients (16.3%) presented with at least one rheumatic AE. The median OS of patients with rheumatic AEs was significantly higher than that of patients without AEs, with 132 weeks (95% CI [69.3-not reached]) and 42.7 weeks (95% CI [25.6-not reached]), respectively (P<0.01). This result remained significant after multivariate analysis (HR 0.54, 95% CI [0.30-0.97], P<0.05). Also, tumor response was better in patients with rheumatic AEs. The occurrence of rheumatic AEs in patients treated with ICIs is associated with better survival and tumor response. Therefore, it seems essential to detect rheumatic AEs as early as possible to allow rapid and optimal management, given the long-term response potential of these patients.

Prior therapies as prognostic factors of overall survival in metastatic castration-resistant prostate cancer patients treated with [177Lu]Lu-PSMA-617. A WARMTH multicenter study (the 617 trial)

IntroductionThe impact of prior therapies, especially chemotherapy, on overall survival (OS) in patients with castration-resistant prostate cancer (CRPC) receiving [177Lu]Lu-PSMA-617 therapy has been the subject of controversy. Therefore, WARMTH decided to plan a multicenter retrospective analysis (the “617 trial”) to evaluate response rate and OS as well as the impact of prior therapies on OS in more than 300 patients treated with 177Lu-PSMA-617.Materials and methodsThe data of 631 metastatic CRPC (mCRPC) patients from 11 different clinics were evaluated. According to the inclusion and exclusion criteria, all patients had to have received at least abiraterone or enzalutamide prior to [177Lu]Lu-PSMA-617 therapy. The patients were divided into three groups: patients who had received prior chemotherapy, patients who avoided chemotherapy, and patients for whom a chemotherapy was contraindicated.ResultsThe analysis included the data of 416 patients, with a median age of 71.9 years. At the time of analysis, 87 patients (20,9%) were still alive. A total of 53.6% of patients had received both abiraterone and enzalutamide; 75.5% and 26.4% had a history of chemotherapy with docetaxel and cabazitaxel, respectively. A total of 20.4% had had Ra-223. The median OS was 11.1 months. Prior chemotherapy, the existence of bone and liver metastases, as well as Eastern Cooperative Oncology Group (ECOG) status, were significant prognosticators of worse overall survival in both univariate and multivariate analyses. Patients without any prior chemotherapy showed a significantly longer OS (14.6 months). The median OS in patients who received one or two lines of chemotherapy with docetaxel or docetaxel followed by cabazitaxel, respectively, was 10.9 months and 8.9 months. There was no difference in OS between patients who had not received chemotherapy and patients for whom chemotherapy was contraindicated. The other prior therapies did not have any significant impact on OS.ConclusionIn the present multicenter analysis, chemotherapy-naïve mCRPC patients receiving [177Lu]Lu-PSMA-617 therapy had a significantly longer OS than patients with a history of chemotherapy. This remained independent in the multivariate analysis besides presence of bone and liver metastases as negative prognosticators for survival, whereas an ECOG of 0–1 is associated with a longer OS.

Effect of Co-Mutations and FLT3-ITD Variant Allele Frequency (VAF) on Response to Quizartinib or Salvage Chemotherapy (SC) in Relapsed/Refractory (R/R) Acute Myeloid Leukemia (AML)

Effect of Co-Mutations and FLT3-ITD Variant Allele Frequency (VAF) on Response to Quizartinib or Salvage Chemotherapy (SC) in Relapsed/Refractory (R/R) Acute Myeloid Leukemia (AML)

Impact of pretreatment serum creatinine on outcomes in pancreatic adenocarcinoma.

e15749 Background: Pancreatic Adenocarcinoma (PA) is an aggressive malignancy with an estimated 5-year survival of 8.5%. PA was responsible for 7.3% of all cancer deaths in 2018 in the US. We aimed to evaluate the impact of pretreatment serum creatinine (SCr) level on Overall Survival (OS) in patients with PA. Methods: A retrospective review of electronic health records of patients with PA seen at our institution between 01/2014 and 01/2018 was done. We collected patients’ SCr at the time of diagnosis, and excluded patients with a glomerular filtration rate (GFR) below 60 mL/min per 1.73 m2 or SCr &gt; 1.3 mg/dL. Patients were dichotomized around a SCr of 0.5 mg/dL. Kaplan-Meier survival estimate was performed to evaluate statistical significance. Results: A total of 83 patients, including 37 females and 46 males, with a median age at diagnosis of 67 years, were included. SCr of &lt; 0.5 mg/dL was associated with a lower median OS as compared to a SCr of ≥0.5 mg/dL, (253 days versus 364 days; P = 0.035). There were more female patients in the low SCr group (71% vs 39%, P = 0.027). Patients with SCr of &lt; 0.5 mg/dL had a lower mean BMI compared to patients with a SCr of ≥0.5 mg/dL, however this was not statistically significant (BMI = 22.45 versus 25.72; P = 0.49). Conclusions: Low SCr is predictive of a lower median OS in patients with PA. SCr has been suggested as a surrogate marker for muscle mass, which is closely associated with the degree of cancer cachexia. Our finding emphasizes the need for future larger studies to evaluate the utility of SCr as a prognostic indicator, as well as a cost-effective surrogate for measuring cancer cachexia. [Table: see text]

Time to first treatment is an independent prognostic factor for multiple myeloma (MM).

e19523 Background: Previous studies have shown a disparity in outcomes of MM between clinical trials and real-world practice. This could be partly due to clinical trial exclusion of patients who need urgent treatment due to high burden of disease or significant illness. In this study, we aim to analyze the impact of time to initiation of systemic therapy for MM on overall survival (OS). Methods: We included MM patients reported to National Cancer Data Base (2004-2014). We excluded 2,860 patients with suspected smoldering MM due to initial treatment beyond 120 days. Relative risk of delayed time to systemic therapy was assessed by logistic regression model. Kaplan-Meier method and Cox multivariate analysis were used to evaluate the association between time to therapy and OS. Results: A total of 53, 519 MM patients were included. Median time to systemic therapy in our cohort was 18 days (range 0-120). Of the entire cohort, 24% patients received systemic therapy for MM &lt; 7 days from diagnosis, and 32% received it after 30 days. Factors associated with time to systemic therapy &gt; 30 days were Black race (OR 1.12, CI 1.07-1.16), female sex (OR 1.10, CI 1.06-1.14), lower Charlson comorbidity score (OR 1.36, CI 1.28-1.45), and academic facility (OR 1.18, CI 1.13-1.24). The median OS for patients who initiated therapy &gt; 30 days after diagnosis was longer than those who received it within 7 days (37 vs. 29 month, p &lt; 0.001). Similarly, on multivariate analysis, patients who received treatment &gt; 30 days after diagnosis were found to have a lower mortality as compared to those who initiated treatment &lt; 7 days (HR 0.81, CI 0.79-0.83; Table). Conclusions: In our study, time to initiation of systemic therapy was an independent prognostic factor in MM. This could be related to the high-risk nature of disease of patients treated within a short duration of diagnosis. These findings have implications for future clinical trial design, which should allow for a pragmatic approach toward enrollment of these high-risk patients to improve external validity. [Table: see text]

Survival in advanced GIST has improved over time and correlates with increased access to post-imatinib tyrosine kinase inhibitors: results from Life Raft Group Registry

BackgroundThe use of imatinib, sunitinib, and regorafenib has transformed the treatment of advanced GIST. Sunitinib and regorafenib improve progression free-survival in the second (2L) and third (3L) line, respectively, compared with placebo. However, the impact of these agents on overall survival (OS) is unclear.MethodsThe Life Raft Group (LRG) patient registry contains records from 1716 GIST patients; 526 have advanced to at least 2L treatment. Patient-reported treatment and outcome data were examined to determine treatment patterns and their impact on OS.ResultsMedian OS from start of 2L therapy was 32.4 months for sunitinib (n = 436) compared with 27.1 months for patients treated with any other 2L drug (n = 74, p = 0.023, HR 1.377) and 16.8 months for patients who never received sunitinib in any treatment line (n = 42, p = 0.028, HR 1.52). In patients reporting progression in 2L, the median OS in patients subsequently receiving 3L regorafenib (n = 53, 26.2 months) was longer than that of 3L patients who never received regorafenib in any line of therapy (n = 174, 14.3 months, p = 0.0002, HR 2.231), and was longer than that of patients who received any other 3L treatment (19.8 months, p = 0.044, HR 1.525). OS for advanced GIST patients in the LRG registry has improved over time (p = 0.0013), correlated with the increased use of TKIs in ≥ 2L settings.ConclusionsIn our analysis, sunitinib and regorafenib significantly improved OS compared with patients who never received these agents. Our data also support the hypothesis that the use of KIT/PDGFRA inhibitors, including non-approved agents, has improved OS for patients with imatinib- and sunitinib-resistant GIST.

Outcomes of Allogeneic Hematopoietic Cell Transplantation in Chronic Myelomonocytic Leukemia: A National Cancer Database Analysis

Introduction Allo-HCT is the only potentially curative therapy for Chronic Myelomonocytic Leukemia (CMML). Objectives To study the impact of allo-HCT on survival of CMML patients. Method We compared the survival outcomes of patients who received (or not) an allo-HCT as a part of their front-line treatment strategy using The National Cancer Database (NCDB) from 2004-2015. Results A total of 8,208 CMML patients were identified, but only 153 were allografted. Median follow-up of survivors was 33.6 months (95% CI=39.6-42.6). Allo-HCT recipients were more likely to be younger, of the male gender, had lower Charlson/Deyo co-morbidity score, had a higher median household income, being treated at an academic facility and having private insurance (Table 1). For survival analysis, we excluded 4484 patients who did not receive front-line therapy to better assess impact of allo-HCT on overall survival (OS). The median OS for patients who received chemotherapy alone or chemotherapy + allo-HCT was 13.3 (95% CI=12.7-14.0) months and 47.4 (14.5-80.4) months, respectively (p Conclusion Allo-HCT is an independent prognostic factor for improved OS in CMML.

Clinical outcomes of bortezomib-based therapy in myeloma.

Bortezomib, a first generation proteasome inhibitor, is used in both newly diagnosed and relapsed myeloma settings. Considerable differences exist in the usage of bortezomib therapy in the clinical practice setting in comparison to clinical trial setting as well manufacturer’s recommendations. These differences include route of administration (intravenous (iv) vs. subcutaneous (sc)), frequency from twice to once weekly, choice of alkylating agent used in combination with bortezomib (melphalan or cyclophosphamide), and choice of glucocorticoids (dexamethasone or prednisolone). We reviewed data from 272 consecutive bortezomib-treated myeloma patients, who received therapy within the regional Thames Valley Cancer Network for both newly diagnosed myeloma (NDMM, n = 120) and relapsed MM (RMM, n = 152). We investigated the influence of age, sex, transplant, bortezomib combinations (doublet vs. triplet), cumulative bortezomib dose per treatment line (<50mg vs. ≥50mg), and route of administration (iv vs. sc) on time to next treatment (TTNT) and on overall survival (OS). Route of bortezomib administration (iv vs. sc) influenced neither OS (41 vs 35 months, p = 0.5), nor TTNT (14 vs. 19 months, p = 0.052). Our study showed a statistically significant improvement in median OS in patients receiving a cumulative dose ≥50mg compared to <50mg (42 vs. 33months, p = 0.003), although presence of confounders need to be taken into account, such as disease stage, performance status, genetic changes and prior therapies. Median OS was longer using triplet therapies compared to a doublet in the RMM cohort (37 vs. 29 months, p = 0.06), although this did not reach statistical significance. Multivariate Cox Regression analysis showed that cumulative bortezomib dose ≥50mg (p = 0.002, HR = 1.83, 95% CI 1.25–2.67) and autologous transplant (p = 0.002, HR = 2.6, 95% CI 1.41–3.98) were both significant factors associated with improved OS. Our data argues in favour of continuing bortezomib for the recommended duration as per Summary of Product Characteristics (SPC), subject to good tolerability, in order to deepen response or extend the duration of best response.

Survival Outcomes for Breast Cancer Patients with Liver Metastases: A Population-Based Study of 3,549 Patients

There are limited published data on the risk factors, incidence, and survival in breast cancer patients with liver metastases. In this study, we aim to utilize the Surveillance, Epidemiology, and End Results (SEER) database to further explore the impact of liver metastases in patients with Stage IV breast cancer. Using the SEER 18 registries, we included 14,932 patients diagnosed with Stage IV breast cancer from 2010-2014 with metastatic disease to the lung, bone, liver, and brain. Kaplan-Meier analyses and multivariate Cox proportional hazard models were utilized to assess the impact of liver metastases on overall survival (OS). The median OS for the entire cohort was 29 months with 43.3% of patients alive at 3 years. 3,549 (23.8%) patients had metastases to liver and 1,045 (7%) patients had liver metastases without involvement of the bone, lung or brain. Patients recorded as having liver metastases in the absence of brain, lung, or bone metastases (HR = 1.36, CI 1.24-1.49, P <0.001), as well as patients recorded as having liver metastases plus additional sites had worse OS than all comers with M1 disease not recorded as in the liver. The median OS for patients with liver metastases at time of diagnosis was 20 months versus 32 months for patients without liver metastases. For patients with liver metastases without involvement of the lung, bone, or brain, median OS was 27 months with only 16% patients alive at 3 years. For patients with liver and lung metastases, median OS was 15 months with only 7.5% patients alive at 3 years. This population-based hypothesis-generating analysis suggests that Stage IV breast cancer patients with liver metastases have worse OS and may benefit from aggressive upfront therapies. These findings may inform future therapeutic investigations to improve the prognosis of breast cancer patients harboring hepatic metastases at presentation.

Abstract 2635: Differential prognostic implications of programmed death-ligand 1 expression on tumor cells and tumor-infiltrating immune cells in patients with locally advanced esophageal squamous cell carcinoma treated with preoperative chemoradiotherapy

Abstract Introduction Previous studies have reported inconsistent results on the prognostic implications of program death-ligand 1 (PD-L1) expression for patients with locoregional esophageal squamous cell carcinoma (ESCC). We evaluated the differential prognostic impacts of the PD-L1 expressions on tumor cells and on tumor infiltrating immune cells in a cohort of locally advanced ESCC patients, receiving neoadjuvant chemoradiotherapy (CRT). Patients and Methods A cohort of 66 patients of locally advanced ESCC have been enrolled to a phase II clinical trial of a single-cycle chemotherapy (a combination of weekly paclitaxel, cisplatin and 24 hour infusional 5-fluorouracil, 2 week on plus one week off, followed by paclitaxel/cisplatin (TP) -based preoperative CRT and radical surgery. Primary tumor tissues were retrospectively collected for PD-L1 immunohistochemical stain by the Clone SP142 antibody (Spring Bioscience, Pleasanton, CA, USA). The expression of PD-L1 was scored as previously reported. Tumor cells (TCs) were scored according to percentage of positively-stained cells: TC3≥50%, TC2≥5% and &amp;lt;50%, TC1≥1% and &amp;lt;5%, and TC0&amp;lt;1%; Immune cells (ICs): IC3≥10%, IC2≥5% and &amp;lt;10%, IC1≥1% and &amp;lt;5%, and IC0&amp;lt;1%. Results PD-L1 expression was evaluable on tumor cells in 49 patients and on immune cells in 51 patients. TC0, TC1, TC2, and TC3 were scored in 27 (55%), 9 (18%), 11 (22%), and 2 (4%) patients, respectively; and IC0, IC1, IC2, and IC3 were in 25 (49%), 9 (18%), 15 (29%), and 2 (4%) patients, respectively. Regression analysis revealed that PD-L1 expressions on TC and IC exhibited different impacts on overall survival (OS): higher PD-L1 expression on TC trended to correlate with worse OS, whereas higher PD-L1 expression on IC trended to correlated with better OS. The median OSs of patients with TC0 and those with TC 1-3 were 52 months and 21 months, respectively, with a hazard ratio (HR) 1.5 (95% confidence interval [CI]: 0.7~3.3; P= 0.27). According to the PD-L1 expressions on TC and IC, patients with TC(+)/IC(+), TC(+)/IC(-), TC(-)/IC(+), TC(-)/IC(-) exhibited median OSs of 26, 7, 42, and 43 months, respectively. Patients with TC(+)/IC(-) PD-L1 expression had significantly worse OS than other patients (HR: 2.6, P=0.03). Among patients with TC(+) PD-L1 expression, those with IC(-) had significantly worse OS than those with IC (+), too (HR: 2.5, P=0.04). Conclusion High PD-L1 expression on TC and low PD-L1 expression on IC associate with inferior prognosis in locally advanced ESCC patients treated with neoadjuvant CRT. (The study was supported by the grant NTUH 104-M2891 and the grant MOST 105-2314-B-002-186-MY3) Citation Format: Ta-Chen Huang, Cher-Wei Liang, Chia-Chi Lin, Ya-Jhen Chen, Kuan-Ling Lin, Chih-Hung Hsu. Differential prognostic implications of programmed death-ligand 1 expression on tumor cells and tumor-infiltrating immune cells in patients with locally advanced esophageal squamous cell carcinoma treated with preoperative chemoradiotherapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2635.

Evolution of Anti-Cancer Treatment and its Impact on Surrogate Prognostic Factors in Multiple Myeloma

Aim. To assess prognostic value of surrogate clinical and laboratory markers in current therapy of multiple myeloma (MM). Materials &amp; Methods. The analysis included 567 patients (215 men and 352 women), the Kirov region inhabitants with newly diagnosed MM over the period from January 1, 1994 to December 31, 2016. The median age was 64 years (range 29-90). Patients were divided into two groups: the first group received treatment from 1994 to 2005 (n = 269), the second group received treatment from 2006 to 2016 (n = 298). Impact of factors on overall survival (OS) was evaluated by multivariate logistic regression analysis using the Cox method. Results. Over the period from 2006 to 2016 the number of patients treated with traditional chemotherapy decreased from 78.4 to 32.5 %. At the same time the number of patients treated with bortezomib-based regimens increased from 1.9 to 56.3 % and autologous hematopoietic stem cell transplantation (auto-HSCT) protocols - from 1.4 to 14.0 %. Median OS over the period from 1994 to 2005 was 27 months. It increased to 55 months in the period of 2006-2016. In the reference decades 5-year overall survival increased from 21 % (95% confidence interval [95% CI] 17-27 %) to 47 % (95% CI 39-55 %), respectively (hazard ratio [HR] 0.51; 95% CI 0.41 0.64; p &lt; 0,0001). In patients treated with bortezomib-based regimens over the period from 2006 to 2016 median OS increased to 73 months compared to 27 months in 19942005. In patients aged &lt; 65 years and treated with auto-HSCT median OS was not reached, and median OS in patients without auto-HSCT treatment was 54 months. Conclusions. Surrogate prognostic markers, such as the age over 65, hemoglobin level &lt; 100 g/L, ß2-microglobulin &gt; 6 mg/L, serum creatinine &gt; 177 pmol/L and stage III according to ISS and Durie-Salmon, are unfavourable predictors of survival of MM patients.

Survival in Patients With Primary Metastatic Renal Cell Carcinoma Treated With Sunitinib With or Without Previous Cytoreductive Nephrectomy: Results From a Population-based Registry

To evaluate the effect of cytoreductive nephrectomy (CN) on overall survival (OS) in primary metastatic renal cell carcinoma (mRCC) patients treated with first-line sunitinib. Patients with primary mRCC treated with first-line sunitinib were selected from a Dutch population-based registry. A propensity score was calculated reflecting the probability of a patient undergoing CN prior to sunitinib using a set of known covariates, such as the Memorial Sloan Kettering Cancer Center and International mRCC Database Consortium risk factors. After propensity score matching, differences in OS were analyzed using the Kaplan-Meier method and a multivariable Cox proportional hazards model was used to evaluate the effect of CN on OS. A total of 227 patients met the selection criteria; 74 patients (33%) underwent CN prior to sunitinib. In the matched population, the median OS of patients who underwent CN was 17.9 months compared to 8.8 months for patients treated with sunitinib only. Multivariable analysis showed that CN was an independent predictor of OS (hazard ratio 0.61, 95% confidence interval: 0.41-0.92). A subgroup analysis of patients with a time to targeted therapy of <1 year showed a median OS of 12.7 months for patients treated with CN compared to 8.0 months for patients treated with sunitinib only. The corresponding hazard ratio was 0.67 (95% confidence interval: 0.46-0.98). This study suggests that CN may be effective. However, the benefit was modest when correcting for time from diagnosis to sunitinib. One important limitation is the use of a registry (with retrospectively collected data), which made it impossible to correct for unmeasured characteristics that could be associated with treatment choices or survival.