Oncology Group Research Articles

Clinical efficacy and safety of immune checkpoint inhibitors plus anlotinib as secondline or subsequent therapy in extensive stage small cell lung cancer: a retrospective study.

Treatments are limited for extensive stage small cell lung cancer (ES-SCLC) patients in secondline or subsequent setting. This study aimed to explore the clinical efficacy and safety of immune checkpoint inhibitors (ICIs) plus anlotinib as secondline or subsequent therapy in ES-SCLC. We retrospectively analyzed 116 patients with ES-SCLC at Shandong Provincial Qianfoshan Hospital between January 2019 and March 2024. According to the different therapy regimes, they were divided into three groups, ICI plus anlotinib as secondline or subsequent therapy group (ICI + anlotinib group), single ICI as secondline or subsequent therapy group (single ICI therapy group), single chemotherapy as secondline therapy group (single chemotherapy group). Kaplan-Meier method was used to compare the progression-free survival (PFS) and the overall survival time (OS) among these three groups. Cox regression analysis was used to analyze different factors which correlated to PFS and OS. The adverse events were assessed according to the Common Terminology Criteria for Adverse Events version 5.0. Kaplan-Meier analysis showed that patients in ICI + anlotinib group had a longer PFS and OS compared to patients in single ICI therapy group (median PFS [mPFS]: 6.7months vs. 4.6months, P = 0.007; median OS [mOS]:12.4months vs. 8.4months, P = 0.041) and single chemotherapy group (mPFS: 6.7months vs. 3.0months, P < 0.001; mOS: 12.4months vs. 7.2months, P = 0.002). The Cox regression analysis showed that the Eastern Cooperative Oncology Group performance status (ECOG PS), liver metastasis, brain metastasis and treatment regimes were independent predictors that affecting the PFS and OS of all the enrolled patients. The common adverse events (AEs) were wleukopenia and fatigue. There was no significant statistical difference in other AEs among the three groups except for leukopenia. ICI + anlotinib as secondline or subsequent therapy has better efficacy than single ICI group and single chemotherapy group and with tolerable toxicities for patients with ES-SCLC.

Biomarker-stratified first-line treatment of right-sided metastatic colon cancer with interdisciplinary collaboration in the IVOPAK II trial.

Patients with right-sided metastatic colon carcinoma have a significantly worse prognosis than those with left-sided colorectal cancer (CRC), regardless of treatment. The aim of the prospective IVOPAK II study was to implement an interdisciplinary guideline-conform personalized CRC palliative therapy of metastatic colorectal carcinoma and to improve the overall survival (OS) by multidisciplinary approach via secondary metastatic resection. We present the efficacy data of first-line treatment and the benefit of interdisciplinary collaboration of right-sided metastatic colon carcinoma patients: n = 25. RAS mutation: n = 20 (80%): received systemic first-line treatment: FOLFIRI plus bevacizumab. All-RAS-wildtype: n = 5 (20%): received systemic first-line treatment: FOLFIRI plus cetuximab. Last date evaluation: 31 January 2024. Median age: 59.6 years (range 42-71), men/women: 14/11. Eastern Cooperative Oncology Group (ECOG) index: 0/1/2 : 11/10/4. Evaluable for response: n = 25. Complete response: n = 0, partial response: n = 14 (56%), stable disease: n = 8 (32%), progressive disease: n = 3 (12%), early tumor shrinkage: n = 13 (52%), estimates progression-free survival: 13 months (95% CI 8-17 months), estimated OS: 48 months (95% CI 25-71 months), median follow-up: 26 months (1-61 months), no evidence of disease: n = 4 (16%). A chemotherapy doublette regimen with FOLFIRI plus a biological as first-line treatment shows promising efficacy and secondary metastatic resection after interdisciplinary discussion was associated with a survival benefit in right-sided metastatic colon carcinoma.

Comparison of augmented Berlin-Frankfurt-Münster (BFM) and BFM 2000 treatment protocols in children diagnosed with high-risk acute lymphoblastic leukemia

Objectives: The main purpose of this study is comparing the augmented Berlin-Frankfurt-Münster (BFM) and BFM 2000 treatment protocols applied to pediatric patients diagnosed with high-risk acute lymphoblastic leukemia (ALL) in our clinic in different years in terms of relapse incidence and survival rates. Methods: When evaluated all patients considering the Children's Oncology Group (COG) criteria, 53 of our patients who were in the medium or high risk group according to the BFM 2000 protocol and were in the high risk group received treatment with Augmented BFM protocol and 17 of them received the BFM 2000 protocol. Age, gender, bone pathology, physical examination, hepatomegaly, splenomegaly, lymphadenopathy, presence of bleeding, hemogram values, immunophenotype, 8th, 14th and 33rd day treatment response, presence of translocation, central nervous system (CNS), extramedullary involvement, risk group, presence of relapse, time to relapse, follow-up period and hospital stay until maintenance treatment were examined. Results: Event-Free Survival (EFS) and Overall Survival (OS) values of patients were 83.6% and 90.1%, respectively. While EFS was 89.4% and OS was 90.6% in the group receiving the Augmented BFM treatment protocol, EFS was calculated as 71.7% and OS was 88.2% in those receiving the BFM-2000 treatment protocol. Accordingly, when the EFS values of those who received the Augmented BFM treatment protocol were compared with those who received BFM-2000, statistically significant values were found (P&amp;lt;0.01). Conclusions: It was observed that the augmented BFM treatment protocol was more protective against relapses and shortened the duration of hospitalization compared to the BFM 2000 treatment protocol.

Assessment of postoperative therapy de-escalation for early-stage, intermediate-risk cervical cancer

ObjectiveThe objective of this study was to assess the oncologic outcome of surgically-treated patients with early-stage, intermediate-risk cervical cancer according to postoperative therapy modality.MethodsThis retrospective cohort study queried the Japanese...

Pembrolizumab in Patients with Advanced Urothelial Carcinoma with ECOG Performance Status 2: A Real-World Study from the ARON-2 Project.

The benefit of immune checkpoint inhibitors (ICIs) for poor performance status patients with advanced urothelial carcinoma (UC) remains unknown. In the present sub-analysis of the ARON-2 study, we investigated the role of pembrolizumab for advanced UC patients with ECOG (Eastern Cooperative Oncology Group) performance status (ECOG-PS) 2. Patients aged ≥18 years with a cytologically and/or histologically confirmed diagnosis of advanced UC progressing or recurring after platinum-based therapy and treated with pembrolizumab between 1 January 2016 to 1 April 2024 were included. In this sub-analysis we focused on patients with ECOG-PS 2. We included 1,040 patients from the ARON-2 dataset; of these, 167 patients (16%) presented an ECOG-PS 2. The median overall survival (OS) was 14.8 months (95% confidence interval (CI) 12.5-16.1) in the overall study population, 18.2 months (95% CI 15.8-22.2) in patients with ECOG-PS 0-1, and 3.7 months (95% CI 3.2-5.2) in subjects with ECOG-PS 2 (p<0.001). The median progression-free survival (PFS) in the overall study population was 5.3 months (95% CI 4.3-97.1), 6.2 months (95% CI 5.5-97.1) in patients with ECOG-PS 0-1, and 2.8 months (95% CI 2.1-3.4) in patients with ECOG-PS 2. Among the latter, liver metastases and progressive disease during first-line therapy were significant predictors of OS at both univariate and multivariate analyses. For PFS, univariate and multivariate analyses showed a prognostic role for lung metastases, liver metastases, and progressive disease during first-line therapy. This large real-world evidence study suggests the effectiveness of second-line pembrolizumab for mUC patients with poor performance status. The presence of liver metastases and progressive disease during first-line therapy is associated with worse clinical outcomes and, thus, should be taken into account when making treatment decisions in clinical practice.

Y90 Radiation Segmentectomy versus Microwave Ablation for Hepatocellular Carcinoma in Locations Suboptimal for Percutaneous Ablation

Abstract Purpose The purpose of our study was to evaluate outcomes following percutaneous microwave ablation (MWA) versus yttrium-90 (Y90) radiation segmentectomy (RS) for tumors in suboptimal locations for ablation. Materials and Methods Retrospective review (January 2014–July 2019) was performed on patients who underwent Y90-RS or MWA (with or without prior transarterial chemoembolization [TACE]) with curative intent for early-stage hepatocellular carcinoma (HCC) lesions in suboptimal locations for percutaneous ablation, defined as locations in which needle placement is within 5 mm of critical structures (liver dome, liver capsule, gallbladder, and hilum). The primary endpoints were treatment response as per the modified Response Evaluation Criteria in Solid Tumors criteria and complications. Statistical Analysis Fischer's exact test was performed for categorical variables, and Student's t-tests for nominal variables. Results Twenty-three lesions in 20 patients (13 male, 67 ± 8.8 years) and 30 lesions in 30 patients (18 male, 62.5 ± 10.6 years) were treated with Y90-RS and MWA (19 with prior TACE), respectively. There were no differences in demographics (p &gt; 0.05). Mean tumor diameter was 2.9 ± 1.0 in those treated with Y90-RS and 2.3 ± 0.9 for MWA (p &lt; 0.05). Lesions were located adjacent to the following structures: dome (n = 22), capsule (n = 16), hilum (n = 9), and gallbladder (n = 6). All patients were Eastern Cooperative Oncology Group performance status 0 to 1. Of the MWA cohort, 19 were Child-Pugh class A, 5 were B, and 6 were C and the mean pretreatment laboratory values were as follows: Model for End-stage Liver Disease sodium (MELD-Na) 12.7 ± 4.6, alpha-fetoprotein (AFP) 848 ± 3168.0, aspartate aminotransferase (AST) 71.9 ± 49.1, alanine aminotransferase (ALT) 48.0 ± 32.4, and total bilirubin 2.4 ± 2.7. Of the Y90-RS cohort, 15 were Child-Pugh class A, 4 were B, and 1 was C and pretreatment laboratory values were as follows: MELD-Na 10.5 ± 3.3 (Y90-RS), AFP 762.2 ± 1793.8 (Y90), AST 50.3 ± 30.5 (Y90), ALT 30.1 ± 16.9 (Y90), and total bilirubin 1.6 ± 1.1 (Y90). Complete response rate following Y90 was 96 versus 76% for MWA, with no disease progression after Y90-RS within the follow-up period. Three (13%) lesions demonstrated progression of disease (time to progression 6.3 months) after MWA. No grade &gt; 2 toxicities or procedure-related complications were noted following Y90-RS. There were 7 major (arterioportal fistula with hemoperitoneum, pneumothorax, liver infarction, and capsular burn) and 3 minor complications following MWA. Conclusion Y90-RS is a valuable alternative to percutaneous MWA as a first-line therapy for early-stage HCC for tumors in suboptimal locations for ablation, offering a favorable treatment response and safety profile.

Development of a scoring system to predict local recurrence in brain metastases following complete resection and observation.

Postoperative stereotactic radiosurgery to the resection cavity in patients with brain metastases is guideline-recommended therapy. However, Japanese Clinical Oncology Group 0504 study showed that postoperative observation could be a therapeutic option in patients with completed resected brain metastases. We hereby investigated the incidence and risk factors for local recurrence after complete resection without immediate radiotherapy and developed a scoring system for its prediction. We included 53 patients with 54 brain metastases, who underwent complete resection between January 2016 and December 2021. We identified risk factors for local recurrence and developed a scoring system to predict it using the extracted risk factors, by assigning one point to each risk factor and calculating the total scores for each patient. We evaluated the correlation between the prognostic score and time to local recurrence. Local recurrence occurred in 37 of 54 tumors (68.5%), with a median follow-up duration of 21.0months. The median time to local recurrence was 5.1months. Univariate and multivariate analyses revealed that non-lung adenocarcinoma, infratentorial tumors, and no postoperative systemic therapy were identified as risk factors for local recurrence (non-lung adenocarcinoma, p = 0.035; infratentorial tumors, p = 0.044; and no postoperative systemic therapy, p = 0.0069). A score ≥ 2 showed a median time to local recurrence of 2.1months, starkly contrasting with 30.8months for a score ≤ 1 (p = 0.0002). Non-lung adenocarcinoma, infratentorial tumors, and no postoperative systemic therapy were risk factors for local recurrence. Our scoring system can predict local recurrence, thus potentially aiding treatment decisions.

36 Real-world treatment patterns and clinical outcomes of metastatic renal cell carcinoma patients post immune-oncology (IO) and Vascular Endothelial Growth Factor (VEGF) receptor targeted therapies

Abstract Background The metastatic renal cell carcinoma (mRCC) treatment landscape has rapidly evolved with approval of newer IO agents and VEGF targeted tyrosine kinase inhibitors (TKIs). However, real-world treatment patterns and clinical outcomes data for mRCC in post IO and TKI setting is limited. The objective of this study is to describe real-world treatment patterns and clinical outcomes of mRCC patients with a prior receipt of IO and TKI therapies in community oncology settings. Methods This retrospective cohort study utilized data from The US Oncology Network (iKnowMed) electronic health record database. The study cohort included adult mRCC patients receiving subsequent line of therapy (LOT; index date) post IO and TKI in combination or sequence between January-18’ and March-23’. All patients were followed from the index date until June-23’ to examine treatment pattern and estimate overall survival (OS), real-world time on treatment (rwToT), and real-world time to next treatment (rwTTNT) by line of therapy (LOT) and individual index regimen (with sample size ≥10). LOT was assigned based on patient’s absolute order of treatment regimen using start and stop dates. OS was defined as the time between Index date and the date of death due to any cause. Descriptive analyses were used to describe patient characteristics and treatment pattern. Time-to-event outcomes (OS, rwToT, and rwTTNT) from index date were summarized using Kaplan-Meier method with a log-rank test by individual regimens. A multivariate analysis using Cox proportional hazards model was performed to assess the association of index regimens with clinical outcomes after controlling for patient characteristics. Results The study cohort included 820 patients. The median age was 66 (range: 58, 72) years, 72.6% were male and 77.1% were Caucasian. Moreover, 60.0% had an Eastern Co-operative Oncology Group (ECOG) performance status of 0-1 and 74.5% had intermediate/poor IMDC risk score. Overall, 253 (30.9%) received index treatment in LOT2, 509 (62.1%) in LOT3 and 58 (7.1%) in LOT4+. The most common treatments post IO and TKI settings were cabozantinib (35.6%), everolimus plus lenvatinib (9.5%), ipilimumab plus nivolumab (7.4%), and axitinib (7.2%). The median OS for LOT2, LOT3, and LOT4 was (18.0, 17.8, and 28.6 months, respectively). The median rwTOT for LOT2 was 2.5 months, LOT3 was 3.5 months, and LOT4 was 6.2 months. The median rwTTNT for LOT2, LOT3, and LOT4 was 6.4, 7.7, and 11.5 months, respectively. Statistically significant difference across individual regimens was observed for OS, rwToT, and rwTTNT (Table). Conclusions This study presents one of the most comprehensive analysis of treatment patterns and clinical outcomes among mRCC patients in the post IO and TKI settings. TKI-with or without IO-based treatments were the most preferred treatments and associated with improved survival. Overall, clinical outcomes in the post IO and VEGF/TKI setting are limited, and novel treatments are needed in this patient population.

Patient Characteristics Associated with Time to Next Treatment in Patients with Ovarian Cancer Treated with Niraparib: The PRED1CT Real-World Study.

Niraparib first-line maintenance (1LM) therapy has demonstrated clinical benefit for patients with ovarian cancer (OC) in clinical trial and real-world settings, but data on factors associated with real-world patient outcomes remain limited. This analysis identified patient characteristics associated with time to next treatment (TTNT), a proxy for real-world progression-free survival, in patients with OC treated with 1LM niraparib monotherapy. This retrospective observational study used a USA nationwide electronic health record-derived deidentified database and included adult patients diagnosed with OC who initiated 1LM niraparib monotherapy after first-line platinum-based chemotherapy. Patients were followed until the earliest occurrence of last clinical activity, death, or end of study period. TTNT was measured from 1LM niraparib initiation to the start of second-line treatment or death. Cox proportional hazards models assessed univariable and multivariable associations between baseline characteristics and TTNT. Of 7872 patients diagnosed with OC, 526 met the eligibility criteria and were included in this analysis. Median (IQR) duration of follow-up was 14.1 (7.4-23.6) months. In univariable analyses, age, BRCA/homologous recombination deficiency (HRD) status, socioeconomic status, stage at initial diagnosis, cytoreductive surgery type, and residual disease status were significantly associated with observed TTNT and were introduced into the multivariable model with other clinically relevant variables. In the multivariable analysis, BRCA/HRD status, cytoreductive surgery type, and residual disease status were significantly associated with observed TTNT after covariate adjustment. Conversely, age, Eastern Cooperative Oncology Group performance status, disease stage, niraparib starting dose status, and first-line bevacizumab use were not associated with observed TTNT. This real-world, retrospective, observational analysis offers valuable insights on prognostic factors associated with TTNT in patients with OC treated with 1LM niraparib monotherapy after first-line platinum-based chemotherapy. Future studies are needed to examine how additional patient characteristics associated with clinical outcomes may guide treatment decisions and improve outcomes.

Predictors of survival in immunotherapy-based treatments in advanced melanoma: a meta-analysis.

The introduction of immunotherapy-based strategies has significantly improved the prognosis for melanoma patients. Nevertheless, some patients still have dismal outcomes, emphasizing the significance of survival predictive indicators in immunotherapy-based approaches. We systematically searched randomized controlled clinical trials investigating dual immunotherapy or chemoimmunotherapy versus placebo or mono-immunotherapy or chemotherapy alone in advanced melanoma patients. R version 4.3.0. was employed to perform all analyses. A comprehensive analysis was conducted on a total of 13,809 patients with advanced melanoma from 19 randomized clinical trials. Immunotherapy-based strategies (alone or in combination) could significantly lengthen the overall survival(OS) and recurrence-free survival (RFS) compared with corresponding controls. Mono-immunotherapy improved RFS and OS in PD-L1 positive patients, in stage AJCC IIIC, and with 4 or morepositive lymph nodes, compared with chemotherapy. Combined immunotherapy statistically improved RFS and OS in those aged < 65, with an Eastern Cooperative Oncology Group (ECOG) status of 0, and LDH ≤ ULN at baseline compared with single treatment alone. Our findings indicated that certain clinicopathological and molecular features could assist in choosing appropriate melanoma patients for immune-based treatments.

Advancing the integration of biosignal-based automated pain assessment methods into a comprehensive model for addressing cancer pain

BackgroundTailoring effective strategies for cancer pain management requires a careful analysis of multiple factors that influence pain phenomena and, ultimately, guide the therapy. While there is a wealth of research on automatic pain assessment (APA), its integration with clinical data remains inadequately explored. This study aimed to address the potential correlations between subjective and APA-derived objectives variables in a cohort of cancer patients.MethodsA multidimensional statistical approach was employed. Demographic, clinical, and pain-related variables were examined. Objective measures included electrodermal activity (EDA) and electrocardiogram (ECG) signals. Sensitivity analysis, multiple factorial analysis (MFA), hierarchical clustering on principal components (HCPC), and multivariable regression were used for data analysis.ResultsThe study analyzed data from 64 cancer patients. MFA revealed correlations between pain intensity, type, Eastern Cooperative Oncology Group Performance status (ECOG), opioids, and metastases. Clustering identified three distinct patient groups based on pain characteristics, treatments, and ECOG. Multivariable regression analysis showed associations between pain intensity, ECOG, type of breakthrough cancer pain, and opioid dosages. The analyses failed to find a correlation between subjective and objective pain variables.ConclusionsThe reported pain perception is unrelated to the objective variables of APA. An in-depth investigation of APA is required to understand the variables to be studied, the operational modalities, and above all, strategies for appropriate integration with data obtained from self-reporting.Trial registrationThis study is registered with ClinicalTrials.gov, number (NCT04726228), registered 27 January 2021, https://classic.clinicaltrials.gov/ct2/show/NCT04726228?term=nct04726228&draw=2&rank=1

Anxiety and depression are common in surgical oncology patients: Results of a prospective cohort study

BackgroundThe oncology patient population is vulnerable to elevated levels of anxiety and depression. These states of psychological distress have been associated with negative effects on treatment course and outcomes, but reported prevalence rates are varied. The General Anxiety Disorder-7 (GAD-7) and Patient Health Questionnaire-9 (PHQ-9) questionnaires are screening tools that can be utilized to assess the levels of anxiety and depression, respectively. MethodsThis prospective, surgeon-blinded study assessed the preoperative prevalence of anxiety and depression in patients with abdominal malignancies who underwent curative-intent resection. Postoperative outcomes and survival were assessed. ResultsOverall, 218 patients were enrolled and included in the final analysis. Patients were stratified into groups by severity of anxiety and depression. 67 (31 %) patients reported at least mild anxiety as defined by GAD-7 score of 5 +, and 74 (34 %) patients reported at least mild depression, as defined by PHQ-9 score of 5 +. Functional status as defined by Eastern Cooperative Oncology Group scores was associated with anxiety (P = 0.003) and depression (P = 0.024). Depression was associated with race and ethnicity (P = 0.014) and marital status (P = 0.021), with Hispanic/Latino and unpartnered patients reporting higher rates of depression. ConclusionAnxiety and depression are common in the surgical oncology population, affecting a third of the patient population in this prospective study. In addition to a thorough social assessment, the GAD-7 and PHQ-9 questionnaires can be utilized preoperatively to identify patients with psychological distress. SynopsisAnxiety and depression were assessed preoperatively in patients with abdominal malignancies who underwent curative-intent resection. These states of psychological distress were highly prevalent, affecting a third of the population, and significantly associated with certain vulnerable groups.

Predicting septic shock in obstructive pyelonephritis associated with ureteral stones: A retrospective study.

To identify the best combination of potential predictors of septic shock in patients with obstructive acute pyelonephritis associated with ureteral stones (OAPN-US) according to Sepsis-3 criteria. Patients who underwent percutaneous nephrostomy (PCN) with OAPN-US were retrospectively evaluated. Recursive feature elimination (RFE) was applied to patients with and without septic shock to identify factors associated with the prediction of progression to septic shock. We compared combinations of the selected features based on area under the receiver operating curve (AUROC) to determine which combination was most effective. This study included 81 patients who were treated with PCN due to OAPN-US. A comparison was made between 37 patients with septic shock (SS) and 44 patients without septic shock (NSS). SS group had a higher age, poorer Eastern Cooperative Oncology Group status, and significantly higher levels of positivity in urine cultures and blood cultures. There were also differences in laboratory tests between the 2 groups. Procalcitonin (PCT), international normalized ratio (INR), and absolute lymphocyte count (ALC) were selected based on RFE. We compared the predictive power for SS when each marker was used alone, when 2 markers were combined, and when all 3 markers were combined. Among these combinations, using all 3 variables together yielded the highest AUROC of 0.942. Of the 3 variables, PCT had the highest Gini importance score, indicating that it was the most influential factor. Clinical characteristics were different between the SS and the NSS groups. In patients with OAPN-US, the combination of PCT, ALC, and INR was an excellent predictor of septic shock.

Induction chemotherapy backbone in frail patients with advanced NSCLC treated with chemotherapy plus pembrolizumab: a single institution retrospective audit of dose intensities from modified regimens.

Guidelines historically recommended mono-chemotherapy for the 1st line treatment of elderly patients with non-small cell lung cancer (NSCLC) and poor performance status (PS). Nowadays, there is no clear indication whether chemo-immunotherapy (chemo-IO) combinations can be effectively delivered in this population. We collected induction chemotherapy data in consecutive patients with advanced NSCLC treated with carboplatin-based chemotherapy regimens plus pembrolizumab, to compute the received dose intensity (RDI) from standard regimens or patient-tailored regimens modified due to age, comorbidities and PS. Comorbidities were stratified according to the comorbidity-polypharmacy score (CPS). The established cut-off of ≥85% for RDI was used to define adequate delivery. 116 pts were treated from Feb-20 to July-23, of whom 96 and 20 with non-squamous and squamous NSCLC, treated with carboplatin-pemetrexed or carboplatin-paclitaxel doublets plus pembrolizumab, respectively. The majority of patients were aged ≥ 70 years (52.6%), the median CPS was 5, with 58.6% having a CPS ≥5, whilst 47.4%, 44.8% and 7.8% had an Eastern Cooperative Oncology Group (ECOG) - PS of 0, 1 and 2, respectively. PD-L1 TPS were <1% in 31.9% and 1-49% in 65.4%. Overall, 47.4% received a priori modified regimens due to poor PS, age, or comorbidities. Among patients with non-squamous NSCLC, median received doses of carboplatin and pemetrexed were 1.37 AUC/week and 138.8 mg/m2/week, with RDIs of 86% and 75% (p < 0.01) for patients treated with standard or modified regimens, respectively. Of note, the RDI was 57.9% among patients with ECOG-PS 2. However, patients treated with modified regimens experienced similar toxicities as those treated with standard regimens, despite being older (p < 0.01), with higher PS (p < 0.01) and more comorbid (p = 0.03). Patients treated with modified regimens achieved a shorter survival (7.1 vs 13.9 months), which is comparable to IO-free historical controls. Among patients with squamous NSCLC, 90% received modified regimens upfront, with median received doses of carboplatin and paclitaxel of 1.19 AUC/week and 40 mg/m2/week, and an overall RDI of 73.5%. Although regimen modifications ensure a safe administration of chemotherapy plus pembrolizumab in frail patients, the RDI seems to be subtherapeutic, especially in those with squamous histology. Dedicated trials are needed to implement combination strategies in this population.

Atezolizumab and chemotherapy for advanced or recurrent endometrial cancer (AtTEnd): a randomised, double-blind, placebo-controlled, phase 3 trial

At the time of AtTEnd trial design, standard treatment for advanced or recurrent endometrial cancer included carboplatin and paclitaxel chemotherapy. This trial assessed whether combining atezolizumab with chemotherapy might improve outcomes in this population. AtTEnd was a multicentre, double-blind, randomised, placebo-controlled, phase 3 trial done in 89 hospitals in 11 countries across Europe, Australia, New Zealand, and Asia. Enrolled patients were aged 18 years or older, and had advanced or recurrent endometrial carcinoma or carcinosarcoma, an Eastern Cooperative Oncology Group performance status of 0-2, and received no previous systemic chemotherapy for recurrence. Patients were randomly assigned (2:1) using an interactive web response system (block size of six) to either atezolizumab 1200 mg or placebo given intravenously with chemotherapy (carboplatin at area under the curve of 5 or 6 and paclitaxel 175 mg/m2 intravenously on day 1 every 21 days) for 6-8 cycles, then continued until progression. Stratification factors were country, histological subtype, advanced or recurrent status, and mismatch repair (MMR) status. Participants and treating clinicians were masked to group allocation. The hierarchically tested co-primary endpoints were progression-free survival (in patients with MMR-deficient [dMMR] tumours, and in the overall population) and overall survival (in the overall population). Primary analyses were done in the intention-to-treat population, defined as all randomly assigned patients who gave their full consent to participation in the study and data processing. Safety was assessed in all patients included in the intention-to-treat population who received at least one dose of study treatment. Here, we report the primary progression-free survival and the interim overall survival results. This study is ongoing and is registered with ClinicalTrials.gov, NCT03603184. Between Oct 3, 2018, and Jan 7, 2022, 551 patients were randomly assigned to atezolizumab (n=362) or placebo (n=189). Two patients in the atezolizumab group were excluded from all analyses due to lack of consent. Median follow-up was 28·3 months (IQR 21·2-37·6). 81 (23%) patients in the atezolizumab group and 44 (23%) patients in the placebo group had dMMR disease by central assessment. In the dMMR population, median progression-free survival was not estimable (95% CI 12·4 months-not estimable [NE]) in the atezolizumab group and 6·9 months (6·3-10·1) in the placebo group (hazard ratio [HR] 0·36, 95% CI 0·23-0·57; p=0·0005). In the overall population, median progression-free survival was 10·1 months (95% CI 9·5-12·3) in the atezolizumab group and 8·9 months (8·1-9·6) in the placebo group (HR 0·74, 95% CI 0·61-0·91; p=0·022). Median overall survival was 38·7 months (95% CI 30·6-NE) in the atezolizumab group and 30·2 months (25·0-37·2) in the placebo group (HR 0·82, 95% CI 0·63-1·07; log-rank p=0·048). The p value for the interim analysis of overall survival did not cross the stopping boundary; therefore, the trial will continue until the required number of events are recorded. The most common grade 3-4 adverse events were neutropenia (97 [27%] of 356 patients in the atezolizumab group vs 51 [28%] of 185 in the placebo group) and anaemia (49 [14%] vs 24 [13%]). Treatment-related serious adverse events occurred in 46 (13%) patients in the atezolizumab group and six (3%) patients in the placebo group. Treatment-related deaths occurred in two patients (pneumonia in one patient in each group). Atezolizumab plus chemotherapy increased progression-free survival in patients with advanced or recurrent endometrial carcinoma, particularly in those with dMMR carcinomas, suggesting the addition of atezolizumab to standard chemotherapy as first-line treatment in this specific subgroup. F Hoffmann-La Roche.

Efficacy and safety of sovleplenib (HMPL-523) in adult patients with chronic primary immune thrombocytopenia in China (ESLIM-01): a randomised, double-blind, placebo-controlled, phase 3 study.

Sovleplenib, a novel spleen tyrosine kinase (SYK) inhibitor, showed promising safety and activity in patients with primary immune thrombocytopenia in a phase 1b/2 trial. We aimed to evaluate the efficacy and safety of sovleplenib in patients with chronic primary immune thrombocytopenia. This randomised, double-blind, placebo-controlled, phase 3 trial (ESLIM-01) was done in 34 clinical centres in China. Eligible patients, aged 18-75 years, had chronic primary immune thrombocytopenia, an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1, and received one or more previous treatments. Patients were randomly assigned (2:1) to receive oral sovleplenib or placebo, 300 mg once daily, for 24 weeks. Randomisation was stratified by baseline platelet counts, previous splenectomy, and concomitant treatment for anti-immune thrombocytopenia at baseline. The primary endpoint was durable response rate (proportion of patients with a platelet count of ≥50 × 109/L on at least four of six scheduled visits between weeks 14 and 24, not affected by rescue treatment) assessed by intention-to-treat. The trial is registered with ClinicalTrials.gov, NCT05029635, and the extension, open-label phase is ongoing. Between Sept 29, 2021, and Dec 31, 2022, 188 patients were randomly assigned to receive sovleplenib (n=126) or placebo (n=62). 124 (66%) were female, 64 (34%) were male, and all were of Asian ethnicity. Median previous lines of immune thrombocytopenia therapy were 4·0, and 134 (71%) of 188 patients had received previous thrombopoietin or thrombopoietin receptor agonist. The primary endpoint was met; durable response rate was 48% (61/126) with sovleplenib compared with zero with placebo (difference 48% [95% CI 40-57]; p<0·0001). The median time to response was 8 days with sovleplenib compared with 30 days with placebo. 125 (99%) of 126 patients in the sovleplenib group and 53 (85%) of 62 in the placebo group reported treatment-emergent adverse events (TEAEs), and most events were mild or moderate. Frequent TEAEs of grade 3 or higher for sovleplenib versus placebo were platelet count decreased (7% [9/126] vs 10% [6/62]), neutrophil count decreased (3% [4/126] vs 0% [0/62]), and hypertension (3% [4/126] vs 0% [0/62]). Incidences of serious TEAEs were 21% (26/126) in the sovleplenib group and 18% (11/62) in the placebo group. There were no deaths in the study. Sovleplenib showed a clinically meaningful sustained platelet response in patients with chronic primary immune thrombocytopenia, with a tolerable safety profile and improvement in quality of life. Sovleplenib could be a potential treatment option for patients with immune thrombocytopenia who received one or more previous therapy. HUTCHMED and Science and Technology Commission of Shanghai Municipality.

Improving Access to Hereditary Testing in Pancreatic Ductal Carcinoma.

Approximately 5%-10% of patients with pancreatic ductal adenocarcinoma (PDAC) have an inherited basis, yet uptake of genetic testing remains low and subject to disparities. This study compared two genetic testing pathways available to patients referred to a provincial cancer center, BC Cancer: a traditional hereditary cancer clinic-initiated testing (HCT) pathway and a new oncology clinic-initiated testing (OCT) pathway. Study subjects were patients with confirmed PDAC referred for genetic testing through the HCT or OCT pathway between June 1, 2020, and February 1, 2022. Charts were retrospectively reviewed for patient characteristics and testing outcomes. The study population was 397 patients (HCT, n = 279 and OCT, n = 118). OCT patients were more likely to have non-European ethnicity compared with HCT patients (41.9% v 25.6%, P = .004), to have earlier-stage disease (P = .012), and to have better Eastern Cooperative Oncology Group performance status than the HCT group (P = .001). A total of 306 patients completed testing (77%). OCT patients had higher test completion rates than HCT patients (odds ratio, 3.74 [95% CI, 1.66 to 9.62]). Median time for results was shorter in OCT than in HCT (53 days [IQR, 44-76] v 107 days [IQR, 63.8-158.3]). Pancreatic cancer susceptibility pathogenic gene variants were identified in 8.5% (26/306). The real-world observations in our study show that oncology clinic-initiated hereditary testing is more effective and faster than testing through hereditary cancer clinic referrals and reaches a more ethnically diverse population. This has important implications for publicly funded environments with limited resources for genetic counseling.

A randomized phase II trial to examine modified vaccinia Ankara-5T4 vaccine in patients with relapsed asymptomatic ovarian cancer (TRIOC)

BackgroundImmunotherapy directed at 5T4 tumor antigen may delay the need for further chemotherapy. An attenuated modified vaccinia Ankara virus containing the gene encoding for 5T4 (MVA-5T4) was studied in asymptomatic...

Augmented use of L-asparaginase markedly improves AYA ALL outcomes: FBMTG Prospective MRD2014 study

The enhanced utilization of native L-Asparaginase (L-Asp) aims to improve treatment outcomes for adult patients with non-Philadelphia chromosome (Ph) acute lymphoblastic leukemia (ALL). In this MRD2014 study, we modified our protocol to include an augmented dose of native L-Asp. Compared to former MRD2008, the total dose of L-Asp was raised from 36,000 U/m2 to 232,000 U/m2 in patients aged 16–35, and from 36,000 U/m2 to 132,000 U/m2 in patients aged 36–65.Adult ALL patients were enrolled between January 2014 and December 2019 based on the following eligibility criteria: non-L3 ALL, 16–65 years of age, Eastern Cooperative Oncology Group performance status of 0–2, and adequate liver and kidney function (serum bilirubin, ≤ 2.0 mg/dl and serum creatinine, ≤ 2.0 mg/dl). ResultsThe median follow-up time was 1128 days (range, 35–2400 days). A total of 81 non-Ph ALL patients (40 males and 41 females; median age 39 years, range 16 to 64 years) in whom MRD status was assessed were included. Complete remission (CR) was achieved in 72 patients (89%). The probability of three-year event-free survival (EFS) and overall survival (OS) in these patients was 55% (95%CI 43–65) and 72% (95%CI 61–81), respectively.The outcomes for patients aged 16–35 demonstrated remarkable improvement. The three-year EFS of MRD2008, at 45% (95%CI 27–62), significantly increased to 71% (95%CI 52–85) for MRD2014 (p = 0.038). Our study unequivocally demonstrated the beneficial effects of augmented use of L-Asp in this adolescent and young adult (AYA) population.This study was registered with the UMIN Clinical Trials Registry (UMIN-CTR), number UMIN000012382.

A sarcopenia screening test predicts mortality among hospitalized cancer patients.

This study investigated the ability of a sarcopenia screening test to predict mortality among cancer inpatients. We conducted a prospective study of patients admitted to the oncology ward of a teaching hospital in southern Taiwan. Over a 5-month period, 82 patients were enrolled for evaluation and were followed for 3 years. All participants received a comprehensive assessment at the time of admission, including Eastern Cooperative Oncology Group (ECOG) performance status, cognitive ability, nutrition index, body mass index, and short physical performance battery (SPPB). Age, ECOG performance status, dementia, SPPB score, and albumin level were associated with sarcopenia. Of the enrolled participants, 53 (64.6%) were diagnosed with sarcopenia. Patients with sarcopenia were associated with worse overall survival (OS) than patients without sarcopenia (28.8% vs. 82%, p = 0.01). Metastasis (hazard ratio [HR]: 5.166; 95% confidence interval [CI]: 1.358-19.656) and albumin level (HR: 4.346; 95% CI: 1.493-12.654) were independent and significant predictors of OS for the whole study population. Age was a predictor of 2-year all-cause mortality among patients aged ≥65 years but not among those aged <65 years (OS: 25.6% vs. 100%, p = 0.04). To summarize, the sarcopenia screening results were found to predict OS and all-cause mortality and may be helpful for patient stratification during in-hospital care.