Eastern Cooperative Oncology Group Performance Status Score Research Articles

Prognosis related to treatment plan in patients with biliary tract cancer: A nationwide database study

BackgroundBiliary tract cancer (BTC) is a malignancy characterized by a low 5-year survival rate (<20 %). Clinical aspects such as tumor resectability, Eastern Cooperative Oncology Group performance status score (ECOG-PS), and molecular profiling are used to determine the treatment for these patients. Diagnosis and treatment are typically established by a multidisciplinary team (MDT). However, standardized practices for BTC are lacking, and there is a need to assess the impact of current MDT treatment decisions on BTC outcomes. The purpose of this study was to investigate the role of the treatment plan proposed by the first MDT conference on survival in patients with BTC, and to identify risk factors for poor survival in this population. MethodThis nationwide, multicenter, retrospective cohort study examined data from the Danish Liver Cancer Group (2013–2020) with confirmed BTC diagnoses. Multiple imputation was used to handle missing data. Survival and variable-survival rate relationships were analyzed using the Kaplan-Meier estimator, and the Cox regression model, respectively. ResultsEligible BTC-confirmed cases: n=1923. The overall median survival was 7.7 months (95 % CI: 7.1–8.5), with a 5-year survival rate of 16.3 %. Patients over 70 years of age, with ECOG-PS 3 or 4, non-operable cases, and with unresectable tumors had lower survival rates. Surgery as the first therapeutic option showed the highest median survival (33.1 months, 95 % CI: 27.2–41.6; p < 0.0001). Multivariable analysis showed that poor ECOG-PS, palliative and neoadjuvant chemotherapy, stereotactic radiotherapy, and best supportive care significantly increased mortality risk in patients with BTC (p=0.05). ConclusionAmong the therapeutic options prescribed by the MDT for patients with BTC, surgery offered the best survival rates, likely due to patient-related prognostic factors. High ECOG-PS was linked to an increased mortality risk regardless of age, highlighting the importance of this criterion in treatment decisions.

Real‑world evidence of advanced non‑small cell lung carcinoma treated with an immune checkpoint inhibitor plus chemotherapy.

Immunotherapy is an effective treatment strategy for patients with advanced non-small cell lung cancer (NSCLC). Although clinical trials on immunotherapy have provided promising results, real-world research in clinical practice is needed to assess the effectiveness and safety of immunotherapy. The present study aimed to characterize real-world outcomes in patients with advanced NSCLC treated with immune checkpoint inhibitor (ICI)-based regimens. The medical records of patients with advanced NSCLC, who were treated with programmed cell death protein-1 (PD-1)/programmed cell death 1 ligand 1 (PD-L1) inhibitors, were reviewed for data collection. The primary objectives were to evaluate progression-free survival (PFS) and overall survival (OS). Therefore, multiple Cox regression models were used to investigate the predictive factors for survival outcomes. Furthermore, survival curves for PFS and OS were created using Kaplan-Meier estimates and compared using the log-rank test. The present study included a total of 133 patients with advanced NSCLC who received therapy with ICIs between January 1, 2019 and December 31, 2022. The final follow-up date was August 24, 2023. The median PFS and OS times were 9.8 and 27.2 months, respectively. Univariate Cox regression analysis demonstrated that sex, clinical stage, PD-L1 status, previous systemic therapy, and brain and liver metastases were associated with PFS, while Eastern Cooperative Oncology Group (ECOG) status, clinical stage, PD-L1 status and brain metastasis were associated with OS. Furthermore, multivariate Cox regression analysis demonstrated that a PD-L1 tumor proportion score (TPS) of ≥50% was an indicator of favorable PFS and OS. An ECOG performance status score of ≥1 was also associated with poor OS but not with PFS. Furthermore, brain metastasis was an indicator for poor PFS and OS, while liver metastasis was only associated with a poor PFS. Finally, the results of the present study demonstrated that PD-L1 status was an independent predictor for PFS and OS in patients with advanced NSCLC, especially adenocarcinoma, who were treated with ICIs plus chemotherapy. The results also suggested that patients with a PD-L1 TPS of ≥50% could benefit when the aforementioned regimens were administrated as a first-line or later-line therapy.

Advancing screening tool for hospice needs and end-of-life decision-making process in the emergency department

BackgroundPredicting mortality in the emergency department (ED) is imperative to guide palliative care and end-of-life decisions. However, the clinical usefulness of utilizing the existing screening tools still leaves something to be desired.MethodsWe advanced the screening tool with the A-qCPR (Age, qSOFA (quick sepsis-related organ failure assessment), cancer, Performance Status Scale, and DNR (Do-Not-Resuscitate) risk score model for predicting one-year mortality in the emergency department of Taipei City Hospital of Taiwan with the potential of hospice need and evaluated its performance compared with the existing screening model. We adopted a large retrospective cohort in conjunction with in-time (the trained and the holdout validation cohort) for the development of the A-qCPR model and out-of-time validation sample for external validation and model robustness to variation with the calendar year.ResultsA total of 10,474 patients were enrolled in the training cohort and 33,182 patients for external validation. Significant risk scores included age (0.05 per year), qSOFA ≥ 2 (4), Cancer (5), Eastern Cooperative Oncology Group (ECOG) Performance Status score ≥ 2 (2), and DNR status (2). One-year mortality rates were 13.6% for low (score ≦ 3 points), 29.9% for medium (3 < Score ≦ 9 points), and 47.1% for high categories (Score > 9 points). The AUROC curve for the in-time validation sample was 0.76 (0.74–0.78). However, the corresponding figure was slightly shrunk to 0.69 (0.69–0.70) based on out-of-time validation. The accuracy with our newly developed A-qCPR model was better than those existing tools including 0.57 (0.56–0.57) by using SQ (surprise question), 0.54 (0.54–0.54) by using qSOFA, and 0.59 (0.59–0.59) by using ECOG performance status score. Applying the A-qCPR model to emergency departments since 2017 has led to a year-on-year increase in the proportion of patients or their families signing DNR documents, which had not been affected by the COVID-19 pandemic.ConclusionsThe A-qCPR model is not only effective in predicting one-year mortality but also in identifying hospice needs. Advancing the screening tool that has been widely used for hospice in various scenarios is particularly helpful for facilitating the end-of-life decision-making process in the ED.

Predictors of efficacy of anamorelin in patients with non‑small cell lung cancer and cachexia: A retrospective study.

Anamorelin, a ghrelin receptor agonist, is approved in Japan for the treatment of cachexia in patients with lung and gastrointestinal cancer. However, there is limited research on the usefulness of anamorelin in clinical settings, therefore, the present study evaluated its efficacy using patient characteristics. A total of 40 patients with non-small cell lung cancer and cachexia who were prescribed anamorelin in the Department of Respiratory Medicine, Hirosaki University Graduate School of Medicine (Aomori, Japan) between July 2021 and November 2022, were retrospectively assessed. Anamorelin was prescribed at a dose of 100 mg once daily to patients who had lost >5% of their body weight within 6 months. All patients were weighed before treatment and those who continued anamorelin treatment for 12 weeks were also weighed at 12 weeks. A logistic regression analysis was used to analyze the association between background characteristics and early discontinuation of treatment with anamorelin (within 4 weeks). The median age was 67 years (range, 36-88), and 65% of the patients were male. There were 24 patients (60.0%) with an Eastern Cooperative Oncology Group Performance Status (ECOG-PS) score 1, 11 patients (27.5%) with an ECOG-PS score 2 and five patients (12.5%) with an ECOG-PS score 3. The early discontinuation group included 11 patients (27.5%). An ECOG-PS score ≥2 (odds ratio, 7.85; 95% confidence interval, 1.43-43.21; P=0.018) was associated with early discontinuation. A total of 18/40 patients (45.0%) were able to continue anamorelin treatment for 12 weeks, and the mean change in body weight was +2.31 kg, which was a significant change from the weight recorded at baseline (P=0.027). The mean changes in lean body mass and soft lean mass between baseline and 12 weeks were +1.97 kg (P=0.14) and +1.26 kg (P=0.15), respectively. The results from the present study indicate that anamorelin is unlikely to be useful for patients with a poor general condition (ECOG-PS score ≥2).

Clinical Outcomes of Cabozantinib in Patients Previously Treated with Atezolizumab/Bevacizumab for Advanced Hepatocellular Carcinoma-Importance of Good Liver Function and Good Performance Status.

(1) Background: This study aimed to investigate clinical outcomes for cabozantinib in clinical practice in patients with advanced hepatocellular carcinoma (HCC) previously treated with atezolizumab plus bevacizumab (Atz/Bev), with a focus on whether patients met criteria of Child-Pugh Class A and Eastern Cooperative Oncology Group performance status (ECOG-PS) score 0/1 at baseline. (2) Methods: Eleven patients (57.9%) met the criteria of both Child-Pugh class A and ECOG-PS score 0/1 (CP-A+PS-0/1 group) and eight patients (42.1%) did not (Non-CP-A+PS-0/1 group); efficacy and safety were retrospectively evaluated. (3) Results: Disease control rate was significantly higher in the CP-A+PS-0/1 group (81.1%) than in the non-CP-A+PS-0/1 group (12.5%). Median progression-free survival, overall survival and duration of cabozantinib treatment were significantly longer in the CP-A+PS-0/1 group (3.9 months, 13.4 months, and 8.3 months, respectively) than in the Non-CP-A+PS-0/1 group (1.2 months, 1.7 months, and 0.8 months, respectively). Median daily dose of cabozantinib was significantly higher in the CP-A+PS-0/1 group (22.9 mg/day) than in the non-CP-A+PS-0/1 group (16.9 mg/day). (4) Conclusions: Cabozantinib in patients previously treated with Atz/Bev has potential therapeutic efficacy and safety if patients have good liver function (Child-Pugh A) and are in good general condition (ECOG-PS 0/1).

Efficacy of immunotherapy in mismatch repair-deficient advanced colorectal cancer in routine clinical practice. An AGEO study

Immunotherapy demonstrated remarkable efficacy in metastatic colorectal cancers (mCRCs) with mismatch repair deficiency (MMRd)/microsatellite instability (MSI). However, data regarding efficacy and safety of immunotherapy in the routine clinical practice are scarce. This is a retrospective, multicenter study aiming to evaluate efficacy and safety of immunotherapy in routine clinical practice and to identify predictive markers for long-term benefit. Long-term benefit was defined as progression-free survival (PFS) exceeding 24 months. All patients who received immunotherapy for an MMRd/MSI mCRC were included. Patients who received immunotherapy in combination with another known effective therapeutic class agent (chemotherapy or tailored therapy) were excluded. Overall, 284 patients across 19 tertiary cancer centers were included. After a median follow-up of 26.8 months, the median overall survival (mOS) was 65.4 months [95% confidence interval (CI) 53.8 months-not reached (NR)] and the median PFS (mPFS) was 37.9 months (95% CI 30.9 months-NR). There was no difference in terms of efficacy or toxicity between patients treated in the real-world or as part of a clinical trial. Overall, 46.6% of patients had long-term benefit. Independent markers associated with long-term benefit were Eastern Cooperative Oncology Group-performance status (ECOG-PS) 0 (P= 0.025) and absence of peritoneal metastases (P= 0.009). Our study confirms the efficacy and safety of immunotherapy in patients with advanced MMRd/MSI CRC in the routine clinical practice. ECOG-PS score and absence of peritoneal metastases provide simple markers that could help identify patients who benefit the most from this treatment.

Early mortality factors in immune checkpoint inhibitor monotherapy for advanced or metastatic non-small cell lung cancer

PurposeImmune checkpoint inhibitors (ICI) are a promising treatment, but may cause hyperprogressive disease and early death. The present study investigated early mortality factors in ICI monotherapy for lung cancer.Patients and methodsWe retrospectively reviewed all patients diagnosed with advanced or metastatic non-small cell lung cancer (NSCLC) and treated with ICI monotherapy (nivolumab, pembrolizumab, and atezolizumab) between March 2016 and August 2021 at National Hospital Organization Kochi Hospital and Tokushima University. Early death was defined as patients who died within 60 days of ICI treatment.ResultsA total of 166 patients were included. The majority of patients (87%) had an Eastern cooperative oncology group (ECOG) Performance status (PS) of 0/1. There were 21 early deaths. Significant differences were observed in ECOG PS, the histological type, liver metastasis, tumor size, the white blood cell count, neutrophils (%), lymphocytes (%), the neutrophil-to-lymphocyte ratio in serum (sNLR), C-reactive protein (CRP), and albumin between the groups with or without early death. Univariate logistic regression analyses identified ECOG PS score ≥ 2, liver metastasis, tumor size ≥ 5 cm, neutrophils ≥ 69%, lymphocytes < 22%, sNLR ≥ 4, CRP ≥ 1 mg/dl, and albumin < 3.58 g/dl as significant risk factors for early death. A multivariate logistic regression analysis revealed that liver metastasis (Odds ratio [OR], 10.3; p = 0.008), ECOG PS score ≥ 2 (OR, 8.0; p = 0.007), and a smoking history (OR, 0.1; p = 0.03) were significant risk factors for early death.ConclusionLiver metastases, ECOG PS score ≥ 2, and a non-smoking history are early mortality factors in ICI monotherapy for advanced or metastatic NSCLC.

Nutrition-inflammation marker enhances prognostic value to ECOG performance status in overweight or obese patients with cancer.

Overweight or obese cancer patients are more likely to develop a proinflammatory status. The aim of this study was to investigate whether the nutrition-inflammation marker can provide additional prognostic information on top of well-established Eastern Cooperative Oncology Group performance status (ECOG-PS) in overweight or obese patients with cancer. A total of 1667 overweight or obese cancer patients were enrolled in this study. We assessed the prediction accuracy of 10 nutrition-inflammation markers by time-dependent receiver operating characteristic (ROC) and elucidated their association with overall survival by the Kaplan-Meier method and a Cox model. In this analysis, the majority of patients had a good performance status (ECOG-PS score ≤1; 88.3%). Both the area under ROC curves and the C-index of the lymphocyte-C-reactive protein ratio (LCR) demonstrated that LCR was the most significant nutrition-inflammation marker correlated with survival. In patients with good ECOG-PS, a low LCR was significantly associated with poorer prognosisand enhanced the predictive ability of one-year mortality. For specific tumor types, a low LCR was an independent prognostic factor for lung cancer, upper gastrointestinal cancer, and colorectal cancer, and it tended to be a significant predictor for breast cancer. In addition, those patients with a combined low LCR and poorer ECOG-PS (ECOG-PS score >1) showed the worst prognosis. The LCR is more strongly associated with overall survival than other nutrition-inflammation markers, and it is able to further detect patients with worse prognosis on top of ECOG-PS in overweight or obese patients with cancer.

Contemporary real-world associations between performance status and clinical outcomes in patients with cancer: A retrospective cohort study.

6578 Background: The ECOG-PS (Eastern Cooperative Oncology Group Performance Status) scale is often used to guide cancer care, but the degree to which it predicts contemporary real-world clinical outcomes, in general and within certain patient groups, is relatively unknown. This retrospective cohort study examined associations between ECOG-PS levels and adverse outcomes in cancer patients with diverse patient characteristics. Methods: Various patient characteristics and nurse-rated ECOG-PS scores (range: 0-4) were recorded for all 21,730 adult patients with cancer receiving intravenous systemic therapy between 01/01/2017 and 12/31/2019 at 18 Kaiser Permanente Northern California cancer centers. Differences in baseline characteristics by ECOG-PS scores were evaluated using chi-square tests for categorical variables and ANOVA for continuous variables. Univariable and multivariable Cox Proportional Hazard models were used to test the ability of ECOG-PS to predict the occurrence of adverse clinical outcomes, including 1-month emergency department (ED) visits and hospitalizations, and 6-month mortality. Results: Overall, 42.5% of patients had ECOG-PS = 0, 42.5% had ECOG-PS = 1, 10.5% had ECOG-PS = 2, 4% had ECOG-PS = 3 and 0.4% had ECOG-PS = 4. Most patients were women (58%), non-Hispanic White (61%), English speakers (93%) and married/domestic partners (63%). African Americans, men, older patients, and those with higher Charlson comorbidity index or Stage IV cancer were found to have higher ECOG-PS levels (all p &lt; 0.001). In multivariable analysis, ECOG-PS of 3-4 were associated with higher ED visits (HR 3.85, 95% CI [3.47-4.26]), hospitalizations (HR 4.7, [4.12-5.36]) and mortality (HR 7.34, [6.64-8.11]), compared with ECOG-PS = 0. Upper gastrointestinal (GI) and Stage IV cancers were associated with a higher risk of ED (upper GI: HR 2.39, [2.12-2.68], (stage IV: HR 1.31, [1.21-1.42]), hospitalization (HR 2.67, [2.27-3.13], (HR 1.51, [1.35-1.68]), and mortality rates (HR 3.37, [2.97-3.81], (HR 1.82, [1.68-1.98]), compared to Breast and Stage I cancers; however, advanced age was not associated with these outcomes. Interactions between ECOG-PS and cancer type as well as ECOG-PS and age group were statistically significant (p &lt; 0.001), such that ECOG-PS was more predictive of adverse outcomes in younger patients and those with breast cancer. Conclusions: In this contemporary real-world cohort, multivariable analysis showed that ECOG-PS, cancer type and stage were strong predictors of ED visits, hospitalizations and mortality; however, advanced age was not. These results also show that ECOG-PS is more predictive of clinical outcomes in certain patient groups. Our findings may have implications on the use of ECOG-PS for clinical decision making.

Comparison of Abiraterone and Combined Androgen Blockade Therapy for High-Risk Metastatic Hormone-Sensitive Prostate Cancer: A Propensity Score-Matched Analysis.

This study aimed to compare the effects of abiraterone acetate plus prednisone (AAP) with androgen deprivation therapy (ADT) with those of combined androgen blockade (CAB) therapy in patients with high-risk metastatic hormone-sensitive prostate cancer (mHSPC). This study retrospectively identified 163 patients with high-risk mHSPC at Kindai University and affiliated hospitals between January 2014 and December 2020. Kaplan-Meier analysis was used to summarize progression-free survival (PFS) and overall survival (OS). Multivariate Cox proportional hazard modeling was used to identify the prognostic factors in the overall cohort. Propensity score matching was used to adjust the clinical characteristics, and log-rank test was applied to these propensity score–matched cohorts. Seventy-four patients who received AAP with ADT and 89 patients who received CAB were included in this study. The median follow-up duration was 27 months (range, 2–89 months). The median PFS and OS were not reached by the AAP+ADT group and 15 and 79 months, respectively, in the CAB group. The Eastern Cooperative Oncology Group (ECOG) performance status (PS) score and AAP+ADT were significant prognostic factors for PFS, whereas ECOG PS score, visceral metastasis, and AAP+ADT were significant prognostic factors for OS. The 2-year PFS was 76.1% in the AAP+ADT group and 38.6% in the CAB group (P < 0.0001), and the 2-year OS was 90.2% in the AAP+ADT group and 84.8% in the CAB group (P = 0.015). In conclusion, AAP+ADT had better PFS and OS than CAB in patients with high-risk mHSPC.

Remote Monitoring of the Performance Status and Burden of Symptoms of Patients With Gastrointestinal Cancer Via a Consumer-Based Activity Tracker: Quantitative Cohort Study.

BackgroundThe number of older patients with gastrointestinal cancer is increasing due to an aging global population. Minimizing reliance on an in-clinic patient performance status test to determine a patient’s prognosis and course of treatment can improve resource utilization. Further, current performance status measurements cannot capture patients' constant changes. These measurements also rely on self-reports, which are subjective and subject to bias. Real-time monitoring of patients' activities may allow for a more accurate assessment of patients’ performance status while minimizing resource utilization.ObjectiveThis study investigates the validity of consumer-based activity trackers for monitoring the performance status of patients with gastrointestinal cancer.MethodsA total of 27 consenting patients (63% male, median age 58 years) wore a consumer-based activity tracker 7 days before chemotherapy and 14 days after receiving their first treatment. The provider assessed patients using the Eastern Cooperative Oncology Group Performance Status (ECOG-PS) scale and Memorial Symptom Assessment Scale-Short Form (MSAS-SF) before and after chemotherapy visits. The statistical correlations between ECOG-PS and MSAS-SF scores and patients’ daily step counts were assessed.ResultsThe daily step counts yielded the highest correlation with the patients' ECOG-PS scores after chemotherapy (P<.001). The patients with higher ECOG-PS scores experienced a higher fluctuation in their step counts. The patients who walked more prechemotherapy (mean 6071 steps per day) and postchemotherapy (mean 5930 steps per day) had a lower MSAS-SF score (lower burden of symptoms) compared to patients who walked less prechemotherapy (mean 5205 steps per day) and postchemotherapy (mean 4437 steps per day).ConclusionsThis study demonstrates the feasibility of using inexpensive, consumer-based activity trackers for the remote monitoring of performance status in the gastrointestinal cancer population. The findings need to be validated in a larger population for generalizability.

Clinician-Based Performance Status and Its Correlation with Patient-Reported Outcomes: Findings from a Prospective Observational Study in Patients with Mantle Cell Lymphoma

Clinician-Based Performance Status and Its Correlation with Patient-Reported Outcomes: Findings from a Prospective Observational Study in Patients with Mantle Cell Lymphoma

Limitations and usefulness of biopsy techniques for the diagnosis of metastatic bone and soft tissue tumors

BackgroundBiopsies are widely used for diagnosing metastatic tumors in the bone and soft tissues; however, their usefulness and limitations remain unclear. Patients and methodsBiopsies of patients (13 men, 8 women, mean age 76 years) with metastatic tumors in the bone (19 patients) and soft tissues (2 patients) were reviewed retrospectively. Investigators surveyed the lesion sites, medical histories, Eastern Cooperative Oncology Group (ECOG) Performance Status (PS), biopsy sites, methods, comorbidities, diagnoses, treatments, and outcomes. ResultsFive patients had multiple lesions, and 16 patients had one lesion. The ECOG PS scores were PS0 (11 patients), PS1 (7 patients), PS2 (2 patients), and PS3 (1 patient). Biopsy sites included pelvic bone (6 cases), rib bone (5 cases), spinal vertebra (7 cases), soft tissue of the shoulder (2 cases), and inner retroperitoneum (1 case). Diagnostic methods included open biopsy (8 patients), core needle biopsy under general (7 patients) or local (3 patients) anesthesia, and computed tomography–guided core needle biopsy under local anesthesia (3 patients). Histology indicated hematological malignancies (9 cases); breast cancer (3 patients); lung cancer, renal cell cancer, cancer of unknown primary (2 cases each); prostate cancer, endometrial (uterine) cancer, and myxoid liposarcoma (1 case each). The primary site identification rate was 90.5%. Outcomes included three patients “dead of disease.“ ConclusionBiopsies are useful for early diagnosis and for the scrutiny of primary lesions of metastatic bone and soft tissue tumors. If the primary tumor is still unknown after biopsy, evidence-based treatment should be initiated promptly.

Performance status as prognostic factor in phase III trials of first-line chemotherapy of unresectable or metastatic pancreatic cancer: A trial-level meta-analysis.

For patients with unresectable or metastatic pancreatic adenocarcinoma (mPDAC), there are no standardized prognostic and predictive factors beyond performance status (PS). A poor PS, as defined by Eastern Cooperative Oncology Group (ECOG) score of 2 or more, has been related with a detrimental effect of chemotherapy. Therefore, even more trials enrolled patients with good PS. The current analysis aims to evaluate the results of PS as a prognostic factor in phase III trials of patients with mPDAC receiving first-line chemotherapy. A literature search on two databases, from 2000 to 2019, and a further selection of clinical trials were performed by predefined criteria. Twelve phase III studies have been included in the analysis: the trials, enrolling 5619 patients, confirmed the worse prognosis of patients with higher ECOG PS scores (hazard ratio [HR] = 1.45; 95% confidence interval [CI], 1.21-1.74; p-value<0.001), and a similar trend was evident for patients with an ECOG PS 1versus 0 (HR = 1.61; 95% CI, 1.43-1.80; p-value<0.001) in six studies, enrolling 2799 patients. Heterogeneity of trials was high, with I2 =91%. Some possible moderators have been suggested, such as the number of drugs in the chemotherapy regimen and the male gender. In conclusion, a low ECOG PS score appears to be related with a longer survival even in trials that excluded patients with an ECOG PS 2 score, but the meta-analyses reported high heterogeneity and publication bias.

Effectiveness and prognostic factors of apatinib treatment in patients with recurrent or advanced cervical carcinoma: A retrospective study.

BackgroundApatinib is an oral anti‐angiogenic drug, its efficacy and prognosis in cervical carcinoma are unclear. This study evaluates the effectiveness and prognostic factors of apatinib in the treatment of recurrent or advanced cervical carcinoma.MethodsPatients with recurrent or advanced cervical cancer, who agreed to take apatinib, were recruited into this single‐center and retrospective study, and administrated apatinib with or without combination of chemo‐ or radio‐therapy until progressive disease (PD) or unacceptable toxicity.ResultsFrom March 2017 to February 2019, 53 patients were reviewed. Among them, 2 (3.77%) patients occurred complete response, 16 (30.19%) patients showed partial response, 27 (50.95%) patients had stable disease, and 8 (15.09%) patients had PD. The objective response rate and disease control rate (DCR) of these patients were 33.96% and 84.91%, respectively. The DCR of patients younger than 50, nonsquamous carcinoma, first‐line apatinib therapy, combined radiotherapy, lesions within radiation field, surgical history, and Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1 were significantly higher than other patients (p < 0.05). The median progression‐free survival (PFS) and overall survival (OS) were 6.0 months (95% CI: 4.43–7.57) and 8.0 months (95% CI: 6.52–9.48), respectively. The univariable and multivariable analysis showed that the patients with an ECOG performance status score of 2 and further line therapy were associated with poor prognosis in both PFS and OS (PFS: HR =8.35, p = 0.000; HR =6.66, p = 0.001; OS: HR = 7.40, p = 0.000; HR = 3.24, p = 0.039), respectively. The most common adverse effects (AEs) were hand‐foot syndrome (35.58%), hypertension (18.87%) and fatigue (15.09%). No grade 3 AEs and drug‐related death occurred.ConclusionThe efficacy and prognosis of patients who are in good general condition and first‐line apatinib combination therapy may be better than other patients. But further phase III clinical trials should be taken to prove this hypothesis.

Association of Performance Status With Survival in Patients With Advanced Non–Small Cell Lung Cancer Treated With Pembrolizumab Monotherapy

Despite approximately 40% of patients having Eastern Cooperative Oncology Group (ECOG) performance status (PS) scores of at least 2 in the real world, most landmark clinical trials that led to the use of pembrolizumab as standard of care in advanced non-small cell lung cancer (NSCLC) excluded this group. To evaluate whether an ECOG PS score of at least 2 at the start of therapy is associated with progression-free survival (PFS) and overall survival (OS) in advanced NSCLC treated with pembrolizumab monotherapy. This cohort study included all consecutive patients with advanced NSCLC who underwent treatment with palliative pembrolizumab monotherapy from February 2016 to October 2019 at a single academic cancer center, with data censoring on January 15, 2020. ECOG PS score at start of therapy, with 0 and 1 indicating fully active or restricted in strenuous activity and scores of 2 and higher indicating increasing disability. PFS and OS, measured from initiation of pembrolizumab monotherapy. Of 74 patients (median [range] age, 68.5 [33-87] years; 36 [48.7%] women; 53 [71.6%] White individuals) with median follow-up of 19.5 (95% CI, 13.4-27.8) months, 45 (60.8%) had an ECOG PS of 0 or 1, while 29 (39.2%) had an ECOG PS of at least 2. There were no significant differences in the baseline characteristics, except in age. Compared with patients with PS scores of 0 or 1, those with PS scores of at least 2 had significantly lower disease control rates (38 [88.4%] vs 15 [53.6%]; P = .002), shorter median PFS (7.9 [95% CI, 4.6-15.4] months vs 2.3 [95% CI, 1.8-4.8] months; P = .004), and shorter median OS (23.2 [14.0 vs 35.7] months vs 4.1 [95% CI, 2.1-6.9] months; P < .001). Among those potentially eligible for subsequent cancer-directed therapy beyond pembrolizumab monotherapy, patients in the group with PS scores of at least 2 were less likely to receive it than those with PS scores of 0 or 1 (2 [8.3%] vs 14 [45.2%]; P = .003). Multivariable adjustment for baseline characteristics confirmed ECOG PS of at least 2 as an independent risk factor for worse PFS (HR, 2.02; 95% CI, 1.09-3.74; P = .03) and worse OS (HR, 2.87; 95% CI, 1.40-5.89; P = .004). In this cohort study, having an ECOG PS score of at least 2 was associated with poorer prognosis for treatment of advanced NSCLC with palliative pembrolizumab monotherapy. Further prospective studies are needed to evaluate more objective and consistent measures of functional status to facilitate identification of patients with borderline performance status who may achieve durable clinical benefit from treatment with pembrolizumab monotherapy.

Clinical implications of germline BCL2L11 deletion polymorphism in pretreated advanced NSCLC patients with osimertinib therapy

IntroductionB-cell lymphoma 2-like 11 (BCL-2-like 11, BCL2L11, also known as BIM) deletion polymorphism (BIM-del) has been associated with resistance to first-generation epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs), and is a poor prognostic factor for EGFR-mutant non-small-cell lung cancer (NSCLC) patients. Nevertheless, the impact of BIM-del in advanced NSCLC patients treated with the third-generation EGFR-TKI osimertinib remains undetermined. This study aims to evaluate the relationship between BIM-del and therapeutic efficacy of osimertinib in pretreated NSCLC patients. MethodsPatients subjected to EGFR T790 M detection and prior osimertinib treatment between December 2015 and December 2019 in our hospital were enrolled in this study. Peripheral blood samples from these patients were collected to detect BIM-del by polymerase chain reaction. Cox proportional hazards models were used to analyze the clinical outcomes of patients with and without BIM-del. ResultsIn total, 152 Chinese Han NSCLC patients—including 143 T790M-positive and nine T790M-negative patients—were enrolled. BIM-del was detected in only 17.5 % of T790M-positive patients (25/143). The majority of patients were aged <65 years (81.8 %, 117/143), were female (58.7 %, 84/143), were non-smokers (82.5 %, 118/143), had Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0–1 (88.8 %, 129/143), and exhibited metastases in the central nervous system (CNS) (54.5 %, 78/143). There were no associations between the BIM-del and clinical characteristics (including age, sex, histology, smoking status, stage, ECOG PS score, and CNS metastases). Patients with BIM-del had a poorer objective response rate than those without (28.0 % versus 52.5 %, p = 0.026). Besides, BIM-del was associated with a significantly shorter progression-free survival (PFS) and a moderately shorter overall survival (OS) (8.3 versus 10.5 months, p = 0.031 and 15.9 versus 25.2 months, p = 0.1, respectively). Multivariate analysis indicated that BIM-del was an independent prognostic factor for PFS but not for OS in EGFR T790 M NSCLC patients. ConclusionsBIM-del is associated with poor clinical responses and outcomes, and might be a negative predictive and prognostic biomarker in EGFR T790 M NSCLC patients with osimertinib treatment.

Survival Analysis of Antineoplastic Treatment for Older Patients with Metastatic Non-Small-Cell Lung Cancer: A Clinical Database Study.

PurposeTo explore whether antineoplastic treatment can improve overall survival (OS) in older patients with metastatic non-small-cell lung cancer (mNSCLC).Patients and MethodsUsing the cancer registry database of a tertiary medical center in Taiwan, we followed patients 65 years old and above with pathologically proved mNSCLC. Chi-square test and Cox regression were used to analyze differences in clinical characteristics, the treatments they received, and factors predicting survival. Kaplan–Meier survival analysis was used to analyze OS differences.ResultsA total of 542 older patients were diagnosed with mNSCLC from 2011 to 2017. Multivariate Cox regression showed that patients receiving targeted therapy (TT) alone, chemotherapy (CT) alone, and crossover (CO) treatment were at significantly less risk of short OS [hazard ratio (HR) 0.351, 95% confidence interval (CI), 0.257–0.479; HR 0.517, CI 0.376–0.711; and HR 0.544, CI 0.373–0.792, respectively]. Patients at significantly increased risk of short OS were those aged ≥85 years and those assigned poorer Eastern Cooperative Oncology Group Performance Status (ECOG-PS) scores (HR 1.513, CI 1.135–2.017, and HR 2.854, CI 2.188–3.724, respectively). The result of Kaplan–Meier survival analysis of 418 patients with ECOG-PS scores 0–2 suggested that patients who received antineoplastic treatments had a significantly better median OS than those receiving supportive care (SC), those receiving TT having the best result (SC, 4.00 months; TT, 21.17 months; CT, 12.83 months; CO, 15.83 months, P<0.001).ConclusionAntineoplastic treatments, especially TT, can improve OS for selected older patients with mNSCLC.

Prognostic value of ECOG performance status and Gleason score in the survival of castration-resistant prostate cancer: a systematic review.

Eastern Cooperative Oncology Group (ECOG) performance status and Gleason score are commonly investigated factors for overall survival (OS) in men with castration-resistant prostate cancer (CRPC). However, there is a lack of consistency regarding their prognostic or predictive value for OS. Therefore, we performed this meta-analysis to assess the associations of ECOG performance status and Gleason score with OS in CRPC patients and compare the two markers in patients under different treatment regimens or with different chemotherapy histories. A systematic literature review of monotherapy studies in CRPC patients was conducted in the PubMed database until May 2019. The data from 8247 patients in 34 studies, including clinical trials and real-world data, were included in our meta-analysis. Of these, twenty studies reported multivariate results and were included in our main analysis. CRPC patients with higher ECOG performance statuses (≥ 2) had a significantly increased mortality risk than those with lower ECOG performance statuses (<2), hazard ratio (HR): 2.10, 95% confidence interval (CI): 1.68–2.62, and P < 0.001. The synthesized HR of OS stratified by Gleason score was 1.01, with a 95% CI of 0.62–1.67 (Gleason score ≥ 8 vs <8). Subgroup analysis showed that there was no significant difference in pooled HRs for patients administered taxane chemotherapy (docetaxel and cabazitaxel) and androgen-targeting therapy (abiraterone acetate and enzalutamide) or for patients with different chemotherapy histories. ECOG performance status was identified as a significant prognostic factor in CRPC patients, while Gleason score showed a weak prognostic value for OS based on the available data in our meta-analysis.

Surufatinib in advanced pancreatic neuroendocrine tumours (SANET-p): a randomised, double-blind, placebo-controlled, phase 3 study

Surufatinib showed superior efficacy in extrapancreatic neuroendocrine tumours (NETs) in the phase 3 SANET-ep study. In SANET-p, we aimed to assess the efficacy and safety of surufatinib in patients with advanced pancreatic NETs. SANET-p was a multicentre, randomised, double-blind, placebo-controlled, phase 3 study, done in 21 hospitals across China. Eligible patients were adults (aged 18 years or older) with progressive, advanced, well differentiated pancreatic NETs, Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, and progression on up to two kinds of previous systemic regimens for advanced disease. Patients were randomly assigned (2:1) via an interactive web response system to receive 300 mg of surufatinib or placebo, taken orally once per day in consecutive 4-week treatment cycles until disease progression, intolerable toxicity, withdrawal of consent, poor compliance, use of other antitumour medication, pregnancy, loss to follow-up, or if the investigator deemed discontinuation in the patient's best interest. Randomisation was done centrally using stratified block randomisation (block size three), stratified by pathological grade, previous systemic antitumour treatment, and ECOG performance status score. Patients, investigators, research staff, and the sponsor study team were masked to treatment allocation. Crossover to surufatinib was permitted for patients in the placebo group with disease progression. The primary endpoint was investigator-assessed progression-free survival in the intention-to-treat population, which included all patients in randomisation. A pre-planned interim analysis was done at 70% of the predicted progression-free survival events. This study is registered at ClinicalTrials.gov, NCT02589821. Between Feb 18, 2016, and Nov 11, 2019, of 264 patients who were screened, 172 (65%) patients were randomly assigned to receive surufatinib (n=113) or placebo (n=59). The median follow-up was 19·3 months (95% CI 9·3-19·4) in the surufatinib group and 11·1 months (5·7-35·9) in the placebo group. The median investigator-assessed progression-free survival was 10·9 months (7·5-13·8) for surufatinib versus 3·7 months (2·8-5·6) for placebo (hazard ratio 0·49, 95% CI 0·32-0·76; p=0·0011). The trial met the early stopping criteria at the interim analysis and was terminated on recommendation from the independent data monitoring committee. The most common grade 3 or worse treatment-related adverse events were hypertension (43 [38%] of 113 with surufatinib vs four [7%] of 59 with placebo), proteinuria (11 [10%] vs one [2%]), and hypertriglyceridaemia (eight [7%] vs none). Treatment-related serious adverse events were reported in 25 (22%) patients in the surufatinib group and four (7%) patients in the placebo group. There were three on-treatment deaths in the surufatinib group, including two deaths due to adverse events (gastrointestinal haemorrhage [possibly treatment-related] and cerebral haemorrhage [unlikely to be treatment-related]), and one death attributed to disease progression. One on-treatment death in the placebo group was attributed to disease progression. Surufatinib significantly improves progression-free survival and has an acceptable safety profile in patients with progressive, advanced pancreatic NETs, and could be a potential treatment option in this patient population. Hutchison MediPharma.