PIK3CB Inhibitor GSK2636771 in Cancers With Mutation/Deletion or Loss of PTEN Protein Expression: Results From the NCI-MATCH ECOG-ACRIN Trial (EAY131) Subprotocols N and P.

Purpose: PTEN loss contributes to aberrant signaling of the phosphatidylinositol 3-kinase (PI3K)/protein kinase B/mammalian target of rapamycin pathway and may confer sensitivity to therapies targeting the PI3K pathway. The PIK3CB inhibitor GSK2636771 demonstrated efficacy in tumors with mutations and may similarly show efficacy in patients with PTEN loss.

Methods: Two nonrandomized, open-label phase II subprotocols within the context of the NCI-MATCH trial targeted PTEN tumor alterations in patients with advanced relapsed/refractory solid tumors, lymphoma, or myeloma: mutation/deletion (arm N) or loss of PTEN protein expression (arm P).

Ten-year survival rates by PSA nadir in patients with metastatic hormone-sensitive prostate cancer: long-term survival analysis from the ECOG-ACRIN 3805 (CHAARTED) trial.

Background: The CHAARTED trial investigated the long-term survival of patients with metastatic hormone-sensitive prostate cancer (mHSPC) treated with androgen deprivation therapy (ADT) with or without docetaxel (D). This analysis focuses on 10-year overall survival (OS) stratified by disease volume and on-therapy PSA levels at 6 months.

Methods: OS was calculated using the Kaplan-Meier method from randomization to death or last known alive date.

Randomized phase II clinical trial of cisplatin/carboplatin and etoposide (PE) alone or in combination with nivolumab as frontline therapy for extensive-stage small cell lung cancer (ES-SCLC): ECOG-ACRIN EA5161.

Purpose: Nivolumab showed durable responses in patients with small cell lung cancer (SCLC). A randomized phase II study investigating nivolumab plus cisplatin/carboplatin and etoposide (PE) versus PE for patients with untreated extensive-stage (ES) SCLC was conducted.

Methods: Patients with untreated ES-SCLC, Eastern Cooperative Oncology Group performance status 0-1, were randomized 1:1 to nivolumab 360 mg intravenously (IV) plus cisplatin 75 mg/m or carboplatin area under the curve 5 on day 1 and etoposide 100 mg/m (PE) on days 1-3 every 21 days for four cycles followed by nivolumab 240 mg intravenously (arm A) every 2 weeks on a 6-week cycle for up to 2 years or PE alone (Arm B) for 4 cycles followed by observation.

Long-Term Follow-Up of E3311, an ECOG-ACRIN Cancer Research Group Phase II Trial of Transoral Surgery and Risk-Based Adjuvant Treatment in Human Papillomavirus-Initiated Oropharynx Cancer.

This phase II trial of transoral surgery (TOS) with deintensified postoperative management in human papillomavirus (HPV)-associated oropharynx cancer (OPC) enrolled patients with resectable cT1-2 stage III/IV American Joint Committee on Cancer (AJCC) seventh edition p16+ OPC without matted neck nodes. Those with clear margins, 0-1 + nodes (LN), and no extranodal extension (ENE) were observed (arm A); those with clear margins, 2-4 + LN, or ENE ≤1 mm were randomly assigned to 50 Gy (arm B) or 60 Gy (arm C); and those with involved margins, >4 + LN, or >1 mm ENE received weekly cisplatin and 60-66 Gy (arm D). Among 359 evaluable patients, the 54-month progression-free (PFS) and overall survival (OS) were 90.

A Phase II Randomized Study of Paclitaxel Alone or Combined with Pelareorep with or without Avelumab in Metastatic Hormone Receptor-Positive Breast Cancer: The BRACELET-01/PrE0113 Study.

Purpose: Pelareorep (Pel) is a type 3 oncolytic reovirus that upregulates PD-L1 expression. We determined the objective response rate (ORR) with paclitaxel (Pac), Pac + Pel, or Pac + Pel + avelumab (Ave).

Patients And Methods: Patients with hormone receptor-positive, HER2-negative metastatic breast cancer who had progressed on at least one line of endocrine therapy with a cyclin-dependent kinase 4/6 inhibitor and had not received chemotherapy for metastatic breast cancer were eligible.

Genetic Drivers of Quality of Life in Prostate Cancer: An Evaluation of Genetic Polymorphisms and Patient-reported Outcomes in the E3805 CHAARTED trial.

Background And Objective: The rs4680 single-nucleotide polymorphism (SNP) of the COMT gene leads to a reduction in dopamine clearance, resulting in better mood and a decrease in symptoms in noncancer populations, but its influence on quality of life (QOL) during cancer treatment is undefined. We hypothesized that in comparison to wildtype (WT) COMT, the rs4680 SNP is associated with better QOL among men with metastatic hormone-sensitive prostate cancer receiving androgen deprivation therapy ± docetaxel (ADT ± D).

Methods: In this post hoc analysis, we tested the association between COMT rs4680 status and Functional Assessment of Cancer Therapy-Prostate (overall QOL), Functional Assessment of Chronic Illness Therapy-Fatigue, and Brief Pain Inventory scores at baseline and at 3, 6, 9, and 12 mo using Fisher's exact test and the Wilcoxon rank-sum test.

Neoadjuvant Chemotherapy and Surgery versus Surgery for Organ Preservation of T3 and T4a Nasal and Paranasal Sinus Squamous Cell Carcinoma: ECOG-ACRIN EA3163.

Purpose: Neoadjuvant chemotherapy for structure preservation (SP) in nasal and paranasal sinus squamous cell carcinoma (NPNSCC) has been described in single-institution studies but not in randomized studies. EA3163 was a randomized study investigating whether cytoreductive neoadjuvant chemotherapy would improve SP or overall survival (OS).

Patients And Methods: Patients with T3/T4a and select T4b NPNSCC requiring orbital or base of skull (BOS) resection were randomized to surgery (arm A) versus surgery preceded by docetaxel/cisplatin for three cycles (arm B).

Comprehensive Molecular and Genomic Analysis of NCI-MATCH Subprotocol Y: Capivasertib in Patients With an -Mutated Tumor.

Purpose: NCI-MATCH (EAY131) is a precision medicine trial using genomic testing to allocate patients with advanced malignancies to targeted treatments. Arm Y evaluated capivasertib, a pan AKT inhibitor, in patients with an -mutated tumor. Here, we report on the translational objectives of the study, a molecular and genomic analysis of specimens to identify potential biomarkers of response or resistance to capivasertib.

Effectiveness of out-of-pocket cost COMmunication and financial navigation (CostCOM) in cancer patients: Study protocol for ECOG-ACRIN EAQ222CD.

Background: High out-of-pocket costs (OOPC) of cancer treatment and lost income result in financial hardship. There is compelling evidence that OOPC communication complemented by financial navigation and counseling will decrease financial hardship by enabling cancer patients to anticipate and accommodate treatment costs and proactively seek financial assistance.

Methods: This is a two-arm randomized controlled trial enrolling 720 patients with newly diagnosed solid tumors (stratified by non-metastatic vs.

Intracluster correlation coefficients from cluster randomized trials conducted within the NCI Community Oncology Research Program (NCORP).

The intracluster correlation coefficient (ICC) measures the correlation of observations within clusters and is a key parameter for power and sample size calculations for cluster randomized trials (CRTs). To facilitate the design of future CRTs within the National Cancer Institute Community Oncology Research Program (NCORP), all studies from the NCORP website were reviewed to identify completed CRTs. ICCs for primary and secondary outcomes (when available) were ascertained from these trials and summarized in this article as a resource for future trial development.

Phase II Study of Copanlisib in Patients With PTEN Loss: Results From NCI-MATCH ECOG-ACRIN Trial (EAY131) Subprotocols Z1G and Z1H.

Purpose: Copanlisib, a pan-class phosphatidylinositol 3-kinase (PI3K) inhibitor with activity predominantly against the PI3K-delta and PI3K-alpha isoforms, has shown promising results in preclinical cancer models with PTEN loss. Herein, we report the activity and safety data from the Z1G and Z1H subprotocols, which included patients with PTEN loss, of the National Cancer Institute Molecular Analysis for Therapy Choice trial.

Methods: Patients with complete loss of cytoplasmic and nuclear PTEN as determined by immunohistochemistry regardless of mutation or deletion status were included in subprotocol Z1G, and patients with a deleterious mutation in the gene and retained expression of PTEN were included in subprotocol Z1H.

Cigarette Smoking and Symptom Burden: Baseline Results From Nine ECOG-ACRIN Cancer Clinical Trials.

Context: Approximately 11% of cancer survivors smoke postdiagnosis.

Objectives: Understanding the relationship between smoking and perceived cancer-related symptoms may inform tobacco treatment interventions for this population.

Methods: From 2017 to 2021, 740 adults in 9 ECOG-ACRIN trials provided baseline data.

Phase II Study of Defactinib (VS6063) in Patients With Tumors With Loss: Results From the NCI-MATCH ECOG-ACRIN Trial (EAY131) Subprotocol U.

Purpose: The NCI-MATCH trial assigned patients with solid tumors, lymphomas, or multiple myeloma to targeted therapies on the basis of identified genetic alterations from tumor biopsies. In preclinical models, ()-inactivated tumors display sensitivity to focal adhesion kinase (FAK) inhibition. The EAY131-U subprotocol evaluated the efficacy of defactinib, a FAK inhibitor, in patients with -altered tumors.

Next-Generation Sequencing-Based MSI Scoring Predicts Benefit in Mismatch Repair-Deficient Tumors Treated with Nivolumab: Follow-up on NCI-MATCH Arm Z1D.

Purpose: Mismatch repair-deficient (dMMR) tumors have demonstrated favorable responses to immune checkpoint inhibition targeting PD-1. However, more in-depth identification of predictors of response could further refine patient selection for immunotherapy treatment.

Patients And Methods: We undertook integrated evaluation performed on samples collected from 28 of 42 patients enrolled on the NCI-Molecular Analysis for Therapy Choice arm Z1D trial that evaluated PD-1 inhibition treatment with nivolumab in patients with noncolorectal dMMR tumors.

Phase II Study of Sunitinib in Tumors With Mutations: Results From the NCI MATCH ECOG-ACRIN Trial (EAY131) Subprotocol V.

Purpose: The NCI-MATCH study is a tumor-agnostic platform trial enrolling patients to targeted therapies on the basis of genomic alterations. Subprotocol V investigated sunitinib in patients with tumors harboring - mutations.

Methods: EAY131-V, is an open-label, single-arm, phase II study.

Phase II Study of Palbociclib in Patients with Tumors with CDK4 or CDK6 Amplification: Results from the NCI-MATCH ECOG-ACRIN Trial (EAY131) Subprotocol Z1C.

Purpose: Amplification of cyclin-dependent kinase 4 (CDK4) and CDK6 is a feature of a variety of malignancies, and preclinical evidence suggests that inhibition of CDK4/6 is a plausible treatment strategy in these tumors. Subprotocol Z1C of the NCI-Molecular Analysis for Therapy Choice trial was designed to evaluate the CDK4/6 inhibitor palbociclib in CDK4- or CDK6-amplified tumors.

Patients And Methods: Patients had a solid malignancy or lymphoma with progression on at least one systemic therapy for advanced disease or with no standard-of-care therapy available.

Primary Results of NRG-RTOG1106/ECOG-ACRIN 6697: A Randomized Phase II Trial of Individualized Adaptive (chemo)Radiotherapy Using Midtreatment F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography in Stage III Non-Small Cell Lung Cancer.

Purpose: NRG-RTOG0617 demonstrated a detrimental effect of uniform high-dose radiation in stage III non-small cell lung cancer. NRG-RTOG1106/ECOG-ACRIN6697 (ClinicalTrials.gov identifier: NCT01507428), a randomized phase II trial, studied whether midtreatment F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) can guide individualized/adaptive dose-intensified radiotherapy (RT) to improve and predict outcomes in patients with this disease.

Phase II Trial of Afatinib in Patients With -Mutated Solid Tumors Excluding Lung Cancer: Results From NCI-MATCH ECOG-ACRIN Trial (EAY131) Subprotocol A.

Purpose: National Cancer Institute-Molecular Analysis for Therapy Choice (NCI-MATCH) was a multicohort phase 2 trial that assigned patients with advanced pretreated cancers to molecularly targeted therapies on the basis of tumor genomic testing. NCI-MATCH Arm A evaluated afatinib, an EGFR tyrosine kinase inhibitor (TKI) approved for advanced non-small cell lung cancer, in patients with tumors other than lung cancer harboring mutations.

Methods: Patients with advanced pretreated cancers other than lung cancer found to have selected actionable mutations were offered participation in Arm A.

Shorter long-term post-transplant life expectancy may be due to prior chemotherapy for the underlying disease: analysis of 3012 patients with acute myeloid leukemia enrolled on 9 consecutive ECOG-ACRIN trials.

Several studies reported that patients with acute myeloid leukemia (AML) who remain in long-term remission after allogeneic or autologous transplant have a shorter life expectancy, compared to the general population. However, little is known about the life expectancy of adult long-term survivors of AML who were treated with chemotherapy alone without a transplant and there have been no comparisons with survival among the general population. The current study indicates that the life expectancy of AML patients who achieved and maintained CR for at least 3 years is shorter than expected for age in the US population.

Combining antivascular endothelial growth factor and anti-epidermal growth factor receptor antibodies: randomized phase II study of irinotecan and cetuximab with/without ramucirumab in second-line colorectal cancer (ECOG-ACRIN E7208).

Background: Early studies showed promise of combined anti-epidermal growth factor receptor (EGFR) plus anti-vascular endothelial growth factor (VEGF) antibodies for advanced colorectal cancer (CRC), yet this was later rejected as toxic and ineffective in studies not selected for RAS status. We studied advanced KRAS wild-type CRC, as second-line treatment, using irinotecan-cetuximab with or without the anti-VEGF receptor antibody ramucirumab.

Methods: Patients with 1 prior regimen including fluoropyrimidine, oxaliplatin, and bevacizumab, with KRAS wild-type tumors were stratified by Eastern Cooperative Oncology Group Performance Score, time since last chemotherapy, and progression on oxaliplatin to irinotecan-cetuximab (IC) (180 mg/m2 and 500 mg/m2 every 2 weeks) vs modified ICR (irinotecan-cetuximab with ramucirumab 150 mg/m2 and 400 mg/m2 plus 6 mg/kg, respectively).