Genomic and Immune Landscape Comparison of MET Exon 14 Skipping and MET-Amplified Non-small Cell Lung Cancer.

Background: Mutation or amplification of the mesenchymal-epithelial transition (MET) tyrosine kinase receptor causes dysregulation of receptor function and stimulates tumor growth in non-small cell lung cancer (NSCLC) with the most common mutation being MET exon 14 (METex14). We sought to compare the genomic and immune landscape of MET-altered NSCLC with MET wild-type NSCLC.

Methods: 18,047 NSCLC tumors were sequenced with Tempus xT assay.

Combining Dual Checkpoint Immunotherapy with Ablative Radiation to All Sites of Oligometastatic Non-Small Cell Lung Cancer: Toxicity and Efficacy Results of a Phase 1b Trial.

Purpose: Ablative local treatment of all radiographically detected metastatic sites in patients with oligometastatic non-small cell lung cancer (NSCLC) increases progression-free survival (PFS) and overall survival (OS). Prior studies demonstrated the safety of combining stereotactic body radiation therapy (SBRT) with single-agent immunotherapy. We investigated the safety of combining SBRT to all metastatic tumor sites with dual checkpoint, anticytotoxic T-lymphocyte-associated protein 4 (anti-CTLA-4), and anti-programmed cell death ligand 1 (anti-PD-L1) immunotherapy for patients with oligometastatic NSCLC.

A phase 2 trial of chemotherapy plus pembrolizumab in patients with advanced non-small cell lung cancer previously treated with a PD-1 or PD-L1 inhibitor: Big Ten Cancer Research Consortium BTCRC-LUN15-029.

Background: Immunotherapy using a checkpoint inhibitor (CPI) alone or in combination with chemotherapy is the standard of care for treatment-naive patients with advanced non-small cell lung cancer (NSCLC) without driver mutations for which targeted therapies have been approved. It is unknown whether continuing CPI treatment beyond disease progression results in improved outcomes.

Methods: Patients who experienced progressive disease (PD) after a clinical benefit from chemotherapy plus a CPI were enrolled.

An International Phase 2 Study of Pazopanib in Progressive and Metastatic Thyroglobulin Antibody Negative Radioactive Iodine Refractory Differentiated Thyroid Cancer.

Multikinase inhibitors have clinical activity in radioactive iodine refractory (RAIR) differentiated thyroid cancers (DTCs) but are not curative; optimal management and salvage therapies remain unclear. This study assessed clinical effects of pazopanib therapy in RAIR-DTC patients with progressive disease, examining in parallel biomarker that might forecast/precede therapeutic response. Assessment of responses and toxicities and of any association between thyroglobulin (Tg) changes cycle 1 and RECIST (response evaluation criteria in solid tumors) response to pazopanib therapy were prospectively undertaken in Tg antibody negative RAIR-DTC patients.

VcR-CVAD Induction Chemotherapy Followed by Maintenance Rituximab Produces Durable Remissions in Mantle Cell Lymphoma: A Wisconsin Oncology Network Study.

Introduction: VcR-CVAD was developed as an intermediate-intensity induction regimen with maintenance rituximab (MR) to improve remission durations after first-line therapy for mantle cell lymphoma (MCL) in older and younger patients with MCL.

Patients And Methods: Patients with previously untreated MCL received VcR-CVAD induction chemotherapy for 6 cycles (21-day cycles). Patients achieving at least a partial response received rituximab consolidation (375 mg/m × 4 weekly doses) and MR (375 mg/m every 12 weeks × 20 doses).

Adjuvant chemotherapy with or without bevacizumab in patients with resected non-small-cell lung cancer (E1505): an open-label, multicentre, randomised, phase 3 trial.

Background: Adjuvant chemotherapy for resected early-stage non-small-cell lung cancer (NSCLC) provides a modest survival benefit. Bevacizumab, a monoclonal antibody directed against VEGF, improves outcomes when added to platinum-based chemotherapy in advanced-stage non-squamous NSCLC. We aimed to evaluate the addition of bevacizumab to adjuvant chemotherapy in early-stage resected NSCLC.

Assessment of adherence and relative dose intensity with oral chemotherapy in oncology clinical trials at an academic medical center.

Background/Aims Oral chemotherapy is increasingly utilized leaving the patient responsible for self-administering an often complex regimen where adverse effects are common. Non-adherence and reduced relative dose intensity are both associated with poorer outcomes in the community setting but are rarely reported in clinical trials. The purpose of this study is to quantify adherence and relative dose intensity in oncology clinical trials and to determine patient and study related factors that influence adherence and relative dose intensity.

Phase I Dose-Escalation Study of Pilaralisib (SAR245408, XL147) in Combination with Paclitaxel and Carboplatin in Patients with Solid Tumors.

Lessons Learned: Despite involvement of PI3K pathway activation in tumorigenesis of solid tumors, single-agent PI3K inhibitors have shown modest clinical activity.Preclinical evidence suggests that combining PI3K pathway inhibitors and chemotherapy can enhance antitumor effects.In patients with solid tumors, the PI3K inhibitor pilaralisib had a favorable safety profile but did not enhance the antitumor activity of paclitaxel plus carboplatin.

A Randomized Phase II Study of Linsitinib (OSI-906) Versus Topotecan in Patients With Relapsed Small-Cell Lung Cancer.

Lessons Learned: Targeted therapy options for SCLC patients are limited; no agent, thus far, has resulted in a strategy promising enough to progress to phase III trials.Linsitinib, a potent insulin growth factor-1-receptor tyrosine kinase inhibitor, may be one agent with activity against SCLC.Despite lack of a reliable predictive biomarker in this disease, which may have partly contributed to the negative outcome reported here, linsitinib, although safe, showed no clinical activity in unselected, relapsed SCLC patients.

High Specificity in Circulating Tumor Cell Identification Is Required for Accurate Evaluation of Programmed Death-Ligand 1.

Background: Expression of programmed-death ligand 1 (PD-L1) in non-small cell lung cancer (NSCLC) is typically evaluated through invasive biopsies; however, recent advances in the identification of circulating tumor cells (CTCs) may be a less invasive method to assay tumor cells for these purposes. These liquid biopsies rely on accurate identification of CTCs from the diverse populations in the blood, where some tumor cells share characteristics with normal blood cells. While many blood cells can be excluded by their high expression of CD45, neutrophils and other immature myeloid subsets have low to absent expression of CD45 and also express PD-L1.

Bendamustine + rituximab chemoimmunotherapy and maintenance lenalidomide in relapsed, refractory chronic lymphocytic leukaemia and small lymphocytic lymphoma: A Wisconsin Oncology Network Study.

Bendamustine + rituximab (BR) has demonstrated high response rates in relapsed/refractory (R/R) chronic lymphocytic leukaemia (CLL) and small lymphocytic lymphoma (SLL). However, progression-free survival (PFS) after BR is <18 months. This study was designed to determine if maintenance lenalidomide after BR induction could improve PFS in R/R CLL/SLL.

A pharmacodynamically guided dose selection of PF-00337210 in a phase I study in patients with advanced solid tumors.

Purpose: PF-00337210 is an oral, highly selective vascular endothelial growth factor receptor (VEGFR) inhibitor. We evaluated a composite of biomarkers in real time to identify the recommended phase 2 dose (RP2D) and preliminary anticancer activity of PF-00337210.

Patients And Methods: Patients (Pts) with advanced cancers were treated once (QD) or twice daily (BID) with escalating doses.

A phase 2 study of weekly temsirolimus and bortezomib for relapsed or refractory B-cell non-Hodgkin lymphoma: A Wisconsin Oncology Network study.

Background: Proteasome inhibitors and mammalian target of rapamycin inhibitors each have activity in various B-cell malignancies and affect distinct cellular pathways. Their combination has demonstrated synergy in vitro and in mouse models.

Methods: The authors conducted a single-arm, phase 2 trial of combined temsirolimus and bortezomib in patients with relapsed and refractory B-cell non-Hodgkin lymphoma (NHL) using a dosing scheme that was previously tested in multiple myeloma.

A phase II study of sorafenib, oxaliplatin, and 2 days of high-dose capecitabine in advanced pancreas cancer.

Purpose: Fluoropyrimidines and oxaliplatin have demonstrated some efficacy against pancreatic adenocarcinoma, but survival remains brief. Sorafenib is an oral multikinase inhibitor which we sought to combine with a unique capecitabine and oxaliplatin regimen for pancreatic adenocarcinoma.

Methods: We performed a multicenter phase II study of sorafenib 200 mg orally twice daily along with oxaliplatin 85 mg/m(2) IV on days 1 and 15, followed by capecitabine 2250 mg/m(2) orally every 8 h for six doses starting on days 1 and 15 of a 28-day cycle in patients who had no more than one previous chemotherapy regimen for their pancreatic adenocarcinoma.

Phase 1 trial of bevacizumab with concurrent chemoradiation therapy for squamous cell carcinoma of the head and neck with exploratory functional imaging of tumor hypoxia, proliferation, and perfusion.

Purpose: A phase 1 trial was completed to examine the safety and feasibility of combining bevacizumab with radiation and cisplatin in patients with locoregionally advanced squamous cell carcinoma of the head and neck (HNSCC) treated with curative intent. Additionally, we assessed the capacity of bevacizumab to induce an early tumor response as measured by a series of biological imaging studies.

Methods And Materials: All patients received a single induction dose of bevacizumab (15 mg/kg) delivered 3 weeks (±3 days) before the initiation of chemoradiation therapy.

Yttrium 90-ibritumomab tiuxetan plus rituximab maintenance as initial therapy for patients with high-tumor-burden follicular lymphoma: a Wisconsin Oncology Network study.

Introduction: Yttrium 90-ibritumomab tiuxetan (90Y-IT) radioimmunotherapy has proved to be effective in relapsed follicular lymphoma (FL). We conducted a clinical trial in which 90Y-IT followed by maintenance rituximab (MR) was evaluated as initial therapy for high-tumor-burden FL.

Methods: Eligible patients had histologically confirmed FL and met the GELF (Groupe d'Etude des Lymphomes Folliculaires) criteria for high tumor burden.

Strategies to prevent brain metastasis in high-risk non-small-cell lung cancer: lessons learned from a randomized study of maintenance temozolomide versus observation.

Background: This study investigated whether maintenance temozolomide (TMZ) after definitive therapy for locally advanced non-small-cell lung cancer (NSCLC) could decrease the incidence of brain metastasis (BM).

Patients And Methods: Eligible patients included those with stage IIIA, IIIB, or IV (for stage IV, only with malignant pleural/pericardial effusion) NSCLC with no BM at diagnosis and stable disease, partial response, or complete response after first-line chemotherapy using at least 2 agents. Patients were randomized to observation or TMZ (75 mg/m(2) for 21 consecutive days followed by a 7-day rest for up to 6 cycles or progression).

A phase I study to determine the maximum tolerated dose and safety of oral LR-103 (1α,24(S)Dihydroxyvitamin D2) in patients with advanced cancer.

Background: The objective of this study was to determine the maximum tolerated dose and safety of LR-103, a Vitamin D analogue, in patients with advanced cancer.

Methods: In Step A, patients received oral LR-103 once daily in 14-day cycles with intra-patient dose escalation per accelerated dose escalation design. Dose limiting toxicity for Step A was defined as ≥grade 2 hypercalcemia and/or >grade 2 other toxicities.

Alkylphosphocholine analogs for broad-spectrum cancer imaging and therapy.

Many solid tumors contain an overabundance of phospholipid ethers relative to normal cells. Capitalizing on this difference, we created cancer-targeted alkylphosphocholine (APC) analogs through structure-activity analyses. Depending on the iodine isotope used, radioiodinated APC analog CLR1404 was used as either a positron emission tomography (PET) imaging ((124)I) or molecular radiotherapeutic ((131)I) agent.

A multicenter phase 2 trial of pazopanib in metastatic and progressive medullary thyroid carcinoma: MC057H.

Context: Pazopanib is a small molecule inhibitor of kinases principally including vascular endothelial growth factor receptors-1, -2, and -3; platelet-derived growth factor receptors-α and -β; and c-Kit. We previously reported a tumor response rate of 49% in patients with advanced differentiated thyroid cancer and 0% in patients with advanced anaplastic thyroid cancer. The present report details results of pazopanib therapy in advanced medullary thyroid cancer (MTC).

Metastasis of primary lung carcinoma to the breast: a systematic review of the literature.

Background: The purpose of this systematic review was to summarize previously published case reports of primary lung carcinoma metastasis to the breast to assess common clinical and pathologic features and management strategies.

Materials And Methods: Case reports describing breast metastasis of primary lung carcinoma were systematically evaluated in MEDLINE and EMBASE.

Results: Thirty-one reported cases of non-small-cell lung carcinoma (NSCLC) metastasized to the breast were identified, along with eight cases of small-cell lung carcinoma.

Feasibility of 4 cycles of docetaxel and cyclophosphamide every 14 days as an adjuvant regimen for breast cancer: a Wisconsin Oncology Network study.

Introduction: Dose-dense therapies have had a major effect on reducing toxicity and improving outcomes in breast cancer. A combination of TC every 3 weeks has emerged as a common chemotherapy regimen used for treatment of node-negative or lower-risk node-positive breast cancer. We tested whether it is feasible to deliver TC on a dose-dense schedule, with therapy completed within 10 weeks.

Paired diagnostic and pharmacodynamic analysis of rare non-small cell lung cancer cells enabled by the VerIFAST platform.

Lung cancer is the leading cause of cancer-related deaths in the United States and worldwide. This has led to major research initiatives focusing on improving early diagnosis rate, as well as the development of pharmacodynamic biomarkers. However, broad clinical integration of these approaches is limited due to the invasive nature of lung biopsies, needle aspirates and resections.

Dose-limiting toxicity after hypofractionated dose-escalated radiotherapy in non-small-cell lung cancer.

Purpose: Local failure rates after radiation therapy (RT) for locally advanced non-small-cell lung cancer (NSCLC) remain high. Consequently, RT dose intensification strategies continue to be explored, including hypofractionation, which allows for RT acceleration that could potentially improve outcomes. The maximum-tolerated dose (MTD) with dose-escalated hypofractionation has not been adequately defined.

A phase I study of vorinostat in combination with bortezomib in patients with advanced malignancies.

Background: A phase I study to assess the maximum-tolerated dose (MTD), dose-limiting toxicity (DLT), pharmacokinetics (PK) and antitumor activity of vorinostat in combination with bortezomib in patients with advanced solid tumors.

Methods: Patients received vorinostat orally once daily on days 1-14 and bortezomib intravenously on days 1, 4, 8 and 11 of a 21-day cycle. Starting dose (level 1) was vorinostat (400 mg) and bortezomib (0.