Receptor tyrosine-protein kinase ERBB3 (HER3) is expressed in most
-mutated lung cancers but is not a known mechanism of resistance to EGFR inhibitors. HER3-DXd is an antibody-drug conjugate ...consisting of a HER3 antibody attached to a topoisomerase I inhibitor payload via a tetrapeptide-based cleavable linker. This phase I, dose escalation/expansion study included patients with locally advanced or metastatic
-mutated non-small cell lung cancer (NSCLC) with prior EGFR tyrosine kinase inhibitor (TKI) therapy. Among 57 patients receiving HER3-DXd 5.6 mg/kg intravenously once every 3 weeks, the confirmed objective response rate by blinded independent central review (Response Evaluation Criteria in Solid Tumors v1.1) was 39% 95% confidence interval (CI), 26.0-52.4, and median progression-free survival was 8.2 (95% CI, 4.4-8.3) months. Responses were observed in patients with known and unknown EGFR TKI resistance mechanisms. Clinical activity was observed across a broad range of HER3 membrane expression. The most common grade ≥3 treatment-emergent adverse events were hematologic toxicities. HER3-DXd has clinical activity in EGFR TKI-resistant cancers independent of resistance mechanisms, providing an approach to treat a broad range of drug-resistant cancers. SIGNIFICANCE: In metastatic
-mutated NSCLC, after disease progression on EGFR TKI therapy, treatment approaches include genotype-directed therapy targeting a known resistance mechanism or chemotherapy. HER3-DXd demonstrated clinical activity spanning known and unknown EGFR TKI resistance mechanisms. HER3-DXd could present a future treatment option agnostic to the EGFR TKI resistance mechanism.
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Gemcitabine plus cisplatin is active in malignant mesothelioma (MM), although single-arm phase II trials have reported variable outcomes. Vascular endothelial growth factor (VEGF) inhibitors have ...activity against MM in preclinical models. We added the anti-VEGF antibody bevacizumab to gemcitabine/cisplatin in a multicenter, double-blind, placebo-controlled randomized phase II trial in patients with previously untreated, unresectable MM.
Eligible patients had an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 and no thrombosis, bleeding, or major blood vessel invasion. The primary end point was progression-free survival (PFS). Patients were stratified by ECOG performance status (0 v 1) and histologic subtype (epithelial v other). Patients received gemcitabine 1,250 mg/m(2) on days 1 and 8 every 21 days, cisplatin 75 mg/m(2) every 21 days, and bevacizumab 15 mg/kg or placebo every 21 days for six cycles, and then bevacizumab or placebo every 21 days until progression.
One hundred fifteen patients were enrolled at 11 sites; 108 patients were evaluable. Median PFS time was 6.9 months for the bevacizumab arm and 6.0 months for the placebo arm (P = .88). Median overall survival (OS) times were 15.6 and 14.7 months in the bevacizumab and placebo arms, respectively (P = .91). Partial response rates were similar (24.5% for bevacizumab v 21.8% for placebo; P = .74). A higher pretreatment plasma VEGF concentration (n = 56) was associated with shorter PFS (P = .02) and OS (P = .0066), independent of treatment arm. There were no statistically significant differences in toxicity of grade 3 or greater.
The addition of bevacizumab to gemcitabine/cisplatin in this trial did not significantly improve PFS or OS in patients with advanced MM.
Abstract Context Palliative care, including symptom management and attention to quality of life (QOL) concerns, should be addressed throughout the trajectory of a serious illness such as lung cancer. ...Objectives This study tested the effectiveness of an interdisciplinary palliative care intervention for patients with Stage I–IV non–small cell lung cancer (NSCLC). Methods Patients undergoing treatments for NSCLC were enrolled in a prospective, quasi-experimental study whereby the usual care group was accrued first followed by the intervention group. Patients in the intervention group were presented at interdisciplinary care meetings, and appropriate supportive care referrals were made. They also received four educational sessions. In both groups, QOL, symptoms, and psychological distress were assessed at baseline and 12 weeks using surveys which included the Functional Assessment of Cancer Therapy–Lung and the Lung Cancer Subscale, the 12-item Functional Assessment of Chronic Illness Therapy–Spiritual Well-Being, and the Distress Thermometer. Results A total of 491 patients were included in the primary analysis. Patients who received the intervention had significantly better scores for QOL (109.1 vs. 101.4; P < 0.001), symptoms (25.8 vs. 23.9; P < 0.001) spiritual well-being (38.1 vs. 36.2; P = 0.001), and lower psychological distress (2.2 vs. 3.3; P < 0.001) at 12 weeks, after controlling for baseline scores, compared to patients in the usual care group. Patients in the intervention group also had significantly higher numbers of completed advance care directives (44% vs. 9%; P < 0.001), and overall supportive care referrals (61% vs. 28%; P < 0.001). The benefits were seen primarily in the earlier stage patients vs. those with Stage IV disease. Conclusion Interdisciplinary palliative care in the ambulatory care setting resulted in significant improvements in QOL, symptoms, and distress for NSCLC patients.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
PURPOSE Vorinostat, a histone deacetylase inhibitor, exerts anticancer effects by both histone and nonhistone-mediated mechanisms. It also enhances the anticancer effects of platinum compounds and ...taxanes in non-small-cell lung cancer (NSCLC) cell lines. This phase II randomized, double-blinded, placebo-controlled study evaluated the efficacy of vorinostat in combination with carboplatin and paclitaxel in patients with advanced-stage NSCLC. PATIENTS AND METHODS Patients with previously untreated stage IIIB (ie, wet) or IV NSCLC were randomly assigned (2:1) to carboplatin (area under the curve, 6 mg/mL x min) and paclitaxel (200 mg/m(2) day 3) with either vorinostat (400 mg by mouth daily) or placebo. Vorinostat or placebo was given on days 1 through 14 of each 3-week cycle to a maximum of six cycles. The primary end point was comparison of the response rate. Results Ninety-four patients initiated protocol therapy. Baseline patient characteristics were similar between the two arms. The median number of cycles was four for both treatment arms. The confirmed response rate was 34% with vorinostat versus 12.5% with placebo (P = .02). There was a trend toward improvement in median progression-free survival (6.0 months v 4.1 months; P = .48) and overall survival (13.0 months v 9.7 months; P = .17) in the vorinostat arm. Grade 4 platelet toxicity was more common with vorinostat (18% v 3%; P < .05). Nausea, emesis, fatigue, dehydration, and hyponatremia also were more frequent with vorinostat. CONCLUSION Vorinostat enhances the efficacy of carboplatin and paclitaxel in patients with advanced NSCLC. HDAC inhibition is a promising therapeutic strategy for treatment of NSCLC.
Introduction
Preclinical evidence suggests the feedforward cytokine loop of interleukin-6/Janus kinases (JAK)/STAT3 plays a role in epidermal growth factor receptor tyrosine kinase inhibitor (EGFR ...TKI) resistance in
EGFR
-mutated non-small cell lung cancer (NSCLC).
Methods
In this phase 1b study, the JAK1/2 and TANK-binding kinase 1 (TBK1) inhibitor momelotinib was evaluated in combination with erlotinib in patients with EGFR TKI-naive,
EGFR
-mutated NSCLC. After erlotinib lead-in (50, 75, 100, or 150 mg oral daily QD), momelotinib was combined and dose escalated in a 3 + 3 study design. The primary endpoint of maximum tolerated dose (MTD) of momelotinib was determined based on the incidence of dose-limiting toxicities (DLTs) during the first 28-day cycle. Secondary endpoints included efficacy and pharmacokinetics (PK).
Results
Eleven patients were enrolled across 3 dose levels of momelotinib (100 mg QD, 200 mg QD, and 100 mg twice daily BID). The MTD was momelotinib 200 mg QD in combination with erlotinib. Two DLTs of grade 4 neutropenia without fever and grade 3 diarrhea occurred at momelotinib 100 mg BID. Most common treatment-emergent adverse events included diarrhea, dry skin, fatigue, and decreased appetite; the vast majority being grades 1–2. The overall response rate was 54.5% (90% CI 27.1–80.0; all partial) and median progression-free survival was 9.2 months (90% CI 6.2–12.4). Momelotinib did not affect the PK of erlotinib.
Conclusions
The JAK1/2 and TBK1 inhibitor momelotinib in combination with erlotinib did not appear to enhance benefit over the historical data of erlotinib monotherapy in patients with
EGFR
-mutated NSCLC.
ClinicalTrials.gov identifier
NCT02206763.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
To describe a family caregiver communication typology and demonstrate identifiable communication challenges among four caregiver types: Manager, Carrier, Partner, and Lone.
Case studies based on ...interviews with oncology family caregivers.
Each caregiver type demonstrates unique communication challenges that can be identified. Recognition of a specific caregiver type will help nurses to adapt their own communication to provide tailored support.
Family-centered cancer care requires attention to the communication challenges faced by family caregivers. Understanding the challenges among four family caregiver communication types will enable nurses to better address caregiver burden and family conflict.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
The purpose of this article is to review current guidelines and national initiatives to improve the quality of supportive oncology care. Review of the literature in this area has documented important ...advances in supportive oncology. This article focuses on work by the National Consensus Project for Quality Palliative Care and the National Quality Forum. The mandate to improve the quality of care in oncology has been the focus of several national reports, including those by the Institute of Medicine addressing end-of-life care in cancer and cancer survivorship. Patients with cancer face significant needs for support in areas such as pain and symptom management and psychosocial and spiritual support, as well as diverse quality-of-life concerns. These reports recommending changes in practice have been reinforced by clinical practice guidelines developed by the National Consensus Project for Quality Palliative Care and preferred practices defined by the National Quality Forum. This article applies these national mandates and guidelines to the field of supportive care in oncology. Improving the quality of supportive oncology will require commitment by oncology professionals in areas of education, clinical practice, and research.
Background Surgical procedures provide the best chance for cure and long-term survival in non-small cell cancer (NSCLC). Persistent symptoms after surgical procedures are common, and they can ...negatively affect health-related quality of life (HRQOL). The purpose of this study was to examine the long-term effect of an interdisciplinary supportive care intervention to improve HRQOL, psychological distress, and symptoms in lung cancer survivors who were treated surgically. Methods Patients undergoing curative intent resection for NSCLC were enrolled in a prospective sequential design whereby the control group was accrued first, followed by the intervention group. Patients in the intervention group were assessed and presented by nurses at weekly interdisciplinary care meetings before surgical procedures, and received four educational sessions (physical, psychological, social, and spiritual well-being) after surgical procedures. Appropriate symptom management, social work, rehabilitation, and spiritual support interventions were coordinated by the study nurse. In both groups, HRQOL, psychological distress, and symptom severity were assessed at baseline and at 6, 12, 24, 36, and 52 weeks with the use of surveys that included the validated Functional Assessment of Cancer Therapy-Lung (FACT-L), Lung Cancer Subscale (LCS), and Distress Thermometer. Mean survey scores were analyzed with factorial analysis of covariance at 12 months. Results A total of 71 survivors (control = 33; intervention = 38) were accrued. No difference was found in age, baseline performance status, or stage of disease between groups. Patients in the intervention group had significantly less distress (mean, 1.0 versus 4.0; range, 0 to 10; p < 0.001) and more favorable mean FACT-L scores (126.1 versus 98.7; range, 0 to 140; p < 0.001) and LCS scores (29.4 versus 23.6; range, 0 to 32; p < 0.001) at 12 months. The mean scores of all categories of questions in FACT-L (physical, social/family, emotional, and functional well-being) were considerably more favorable in the intervention group at 12 months. Conclusions An interdisciplinary supportive care intervention improves psychological distress and HRQOL at 12 months after lung cancer surgical procedures. This study has important implications in improving HRQOL of lung cancer survivors after surgical procedures. Further study is warranted on incorporating the interdisciplinary personalized interventions used in this study into clinical practice for lung cancer survivors.
JUNIPER compared the efficacy and safety of abemaciclib, a selective cyclin-dependent kinase 4 and 6 inhibitor, with erlotinib in patients with non-small cell lung cancer (NSCLC) harboring a Kirsten ...rat sarcoma (
) mutation.
JUNIPER was a Phase III, multicenter, randomized, open-label trial of abemaciclib versus erlotinib in patients with stage IV NSCLC and a detectable mutation in codons 12 or 13 of the
oncogene, who progressed after platinum-based chemotherapy and 1 additional therapy (could include immune checkpoint inhibitor therapy). Randomized patients (3:2) received either 200 mg abemaciclib twice daily or 150 mg erlotinib once daily with best supportive care until disease progression or unacceptable toxicity. The primary endpoint was overall survival (OS); secondary endpoints included overall response rate (ORR), progression-free survival (PFS), and safety.
Between December 2014 and April 2017, 453 patients were randomly assigned to receive abemaciclib (N = 270) or erlotinib (N = 183). Median OS was 7.4 months (95% confidence interval CI: 6.5, 8.8) with abemaciclib and 7.8 months (95% CI: 6.4, 9.5) with erlotinib (hazard ratio HR = 0.968 95% CI: 0.768, 1.219; p = .77). Median PFS was 3.6 months (95% CI: 2.8, 3.8) with abemaciclib and 1.9 months (95% CI: 1.9, 2.0) with erlotinib (HR = 0.583 95% CI: 0.470, 0.723; p <.000001). ORR was 8.9% and 2.7% (p = .010), and the disease control rate was 54.4% and 31.7% (p <.001) with abemaciclib and erlotinib, respectively. Safety results reflected the known safety profiles of abemaciclib and erlotinib.
In this study, the primary endpoint of OS was not met; PFS and ORR were improved with manageable toxicity in the abemaciclib arm. The increases in response rates and PFS support further investigation of abemaciclib in other NSCLC subpopulations or in combination with other agents.
www.ClinicalTrials.gov, identifier: NCT02152631.
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