Phase I/II Trial of Carboplatin, Nab-paclitaxel, and Pembrolizumab for Advanced Non-Small Cell Lung Cancer: Hoosier Cancer Research Network LUN13-175.

BACKGROUND: Combination chemotherapy and immunotherapy regimens have significantly improved survival for patients with previously untreated advanced non-small cell lung cancer (NSCLC). Improvements in overall survival (OS) in two separate pembrolizumab trials have demonstrated survival improvements over chemotherapy alone, regardless of PD-L1 status. The optimal chemotherapy backbone for combination with immunotherapy is unknown. We hypothesized nab-paclitaxel may be a well-suited platinum partner to use in combination with checkpoint inhibitor therapy for both adenocarcinoma and squamous histology and conducted a phase I/II trial to assess the efficacy of this regimen in advanced NSCLC. METHODS: Adult patients with previously untreated, stage IIIB/IV NSCLC (any histology) with an Eastern Cooperative Oncology Group performance status of 0-1, any PD-L1 expression, and no EGFR mutations or ALK translocations, received carboplatin area under the curve (AUC) 6 day 1, nab-paclitaxel 100 mg/m2 days 1, 8, 15, and pembrolizumab 200 mg day 1 q21 days for 4 cycles followed by maintenance pembrolizumab q3w. Co-primary endpoints were progression-free survival (PFS) and overall response rate (ORR). RESULTS: Forty-six evaluable patients enrolled, 14 in phase I and 32 in phase II, from June 2015 to July 2018 with a median duration of follow-up of 35.4 months. Median time from enrollment to data lock was 42 months. In the ITT population, the ORR was 35%, median PFS was 5.6 months (95% CI, 4.6-8.2), and median OS was 15.4 months (CI, 12.4-28.1). There were no statistical differences in PFS or OS by PD-L1 status. The 2- and 3-year landmark OS rates were 33% and 24%, respectively. CONCLUSION: Carboplatin, nab-paclitaxel, and pembrolizumab are a safe and effective regimen for patients with both squamous and nonsquamous NSCLC. Although this study did not meet the prespecified endpoints, the median and landmark OS results are consistent with durable benefit of this regimen as seen in phase III trials for first-line treatment of advanced 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. Patients received pembrolizumab (200 mg every 3 weeks) plus next-line chemotherapy. The primary end point was progression-free survival (PFS) according to the Response Evaluation Criteria in Solid Tumors (version 1.1). Key secondary end points included the overall survival (OS), clinical benefit rate, and toxicity. The authors' hypothesis was that continuing pembrolizumab beyond progression would improve the median PFS to 6 months in comparison with a historical control of 3 months with single-agent chemotherapy alone. RESULTS: Between May 2017 and February 2020, 35 patients were enrolled. The patient and disease characteristics were as follows: 51.4% were male; 82.9% were current or former smokers; and 74.3%, 20%, and 5.7% had adenocarcinoma, squamous cell carcinoma, and NSCLC not otherwise specified, respectively. The null hypothesis that the median PFS would be 3 months was rejected (p < .05). The median PFS was 5.1 months (95% confidence interval [CI], 3.6-8.0 months). The median OS was 24.5 months (95% CI, 15.6-30.9 months). The most common treatment-related adverse events were fatigue (60%), anemia (54.3%), and nausea (42.9%). There were no treatment-related deaths. CONCLUSIONS: Pembrolizumab plus next-line chemotherapy in patients with advanced NSCLC who experienced PD after a clinical benefit from a CPI was associated with statistically significant higher PFS in comparison with historical controls of single-agent chemotherapy alone.

Surveillance after Complete Response to First-Line Chemotherapy in Patients with Metastatic Nonseminomatous Germ Cell Tumor.

PURPOSE: The optimal management of patients with metastatic germ cell tumors who achieve a complete response (CR) after first-line chemotherapy remains unsettled. This study reports long-term outcomes of patients with metastatic germ cell tumor managed with surveillance after achieving a CR to first-line chemotherapy. MATERIALS AND METHODS: Patients with metastatic nonseminomatous germ cell tumor treated at Indiana University between 1990 and 2017 who achieved a CR after first-line chemotherapy and were monitored with surveillance were retrospectively analyzed. CR was defined as normalization of tumor markers AFP and hCG, and no residual mass >1 cm in long axis. Kaplan-Meier methods were used to analyze progression-free survival (PFS) and overall survival (OS). RESULTS: Three hundred sixty-seven patients achieved a CR and were managed with surveillance. After a median followup of 4.97 years, 34 patients had disease progression. At most recent followup, 346 (94%) patients were alive with no evidence of disease, 10 patients (2.7%) died of their disease, 5 (1.4%) died of other causes and 6 (1.6%) were lost to followup. The estimated 2-year PFS was 91% (95% CI: 87%-94%) and 2-year OS was 98% (95% CI: 96%-99%). The estimated 2-year PFS by International Germ Cell Cancer Collaborative Group risk category was 92% for good vs 90% for intermediate vs 87% for poor risk (p=0.15), and the estimated 2-year OS was 99% for good vs 96% for intermediate vs 93% for poor risk disease (p=0.001). CONCLUSIONS: Patients with metastatic nonseminomatous germ cell tumor who achieve a CR after first-line chemotherapy can be observed. Most patients who relapse can be salvaged with surgery and/or chemotherapy.

A phase II study assessing the safety and efficacy of ASP1650 in male patients with relapsed refractory germ cell tumors.

Claudin6(CLDN6) is a tight junction protein of claudin-tetraspanin family and is of the earliest molecules expressed in embryonic epithelium. CLDN6 is frequently aberrantly expressed in testicular germ-cell tumors(GCT). ASP1650 is a chimeric-mouse/human-IgG1 antibody directed against CLDN6. Two-part, open-label, phase-II trial investigating ASP1650 in patients with relapsed/refractory GCT and no curable options. Part1 was a safety lead-in to establish the recommended-phase-II-dose(RP2D). Part2 was a phase-II study designed to evaluate the antitumor effects of ASP1650. CLDN6 expression was centrally assessed on archival tumor tissue using immunohistochemistry. The primary objectives were to establish the RP2D(safety lead-in) and the antitumor activity(phase-II) of ASP1650. Nineteen male patients were enrolled: 6 patients in 1000 mg/m2 safety lead-in group, and 13 in 1500 mg/m2 group. Median age 37.2 years(range,20-58). Histology was non-seminoma in 17/19 patients. Median number of previous chemotherapy regimens was 3. Thirteen patients had prior high-dose chemotherapy. No dose-limiting toxicity events were reported at any study drug dose. A RP2D of 1500 mg/m2 every 2 weeks was established. No partial or complete responses were observed. The study was stopped at the end of Simon Stage-I due to lack of efficacy. 15/16 subjects with available tissue had CLDN6 positive staining. The mean percent membrane staining was 71.6% and the mean membrane H score was 152.6(SD 76). ASP1650 did not appear to have clinically meaningful single-agent activity in relapsed/refractory GCT. CLDN6 expression seems ubiquitous in all elements of GCT and is worthy of investigation as a diagnostic biomarker and therapeutic target. (Clinical trial information: NCT03760081).

Lung Cancer Screening Knowledge in Four Internal Medicine Programs.

INTRODUCTION: Lung cancer remains the leading cause of cancer-related death in the United States. Low density CT (LDCT) has been shown to reduce mortality in high-risk populations. Recognizing and mitigating gaps in knowledge in early medical training could result in increased utilization of screening CT in high risk-populations. METHODS: An electronic survey was conducted among Internal Medicine (IM) residents at 4 academic programs in the Midwestern United States. A survey was distributed to evaluate knowledge about high-risk populations, mortality benefits, and a comparison in mortality benefits between LDCT and other screening modalities using number needed to screen (NNS). Results: There was a 46.6% (166/360) response rate. Residents correctly answered an average of 2.9/7 (43.1%) questions. PGY-1 (post-graduate year) and PGY-2 residents performed better than PGY-3 (P = .022). Only 1/3 rd of all respondents correctly identified the population needed to be screened. Over 80% of residents thought screening with LDCT had a cancer-specific mortality benefit but were evenly split (except Program 2 residents), on recognizing an all-cause mortality benefit with LDCT, (P = .016). Only 7.7% thought women benefited the most from LDCT. Self-assess and attained knowledge were similar among programs. CONCLUSIONS: LDCT is a noninvasive intervention with a substantial mortality reduction, especially in states with high rates of smoking, and is widely covered by insurers. With average knowledge score less than 50%, this study shows there is a substantial need to increase the knowledge of LCS in IM residency programs.

Relations of perceived injustice to psycho-spiritual outcomes in advanced lung and prostate cancer: Examining the role of acceptance and meaning making.

OBJECTIVE: Many advanced cancer patients struggle with anxiety, depressive symptoms, and anger toward God and illness-related stressors. Patients may perceive their illness as an injustice (i.e., appraise their illness as unfair, severe, and irreparable or blame others for their illness), which may be a risk factor for poor psychological and spiritual outcomes. This study examined relations between cancer-related perceived injustice and psycho-spiritual outcomes as well as potential mediators of these relationships. METHODS: Advanced lung (n = 102) and prostate (n = 99) cancer patients completed a one-time survey. Using path analyses, we examined a parallel mediation model including the direct effects of perceived injustice on psycho-spiritual outcomes (i.e., anxiety, depressive symptoms, anger about cancer, anger towards God) and the indirect effects of perceived injustice on psycho-spiritual outcomes through two parallel mediators: meaning making and acceptance of cancer. We then explored whether these relations differed by cancer type. RESULTS: Path analyses indicated that perceived injustice was directly and indirectly-through acceptance of cancer but not meaning making-associated with psycho-spiritual outcomes. Results did not differ between lung and prostate cancer patients. CONCLUSIONS: Advanced cancer patients with greater perceived injustice are at higher risk for poor psycho-spiritual outcomes. Acceptance of cancer, but not meaning making, explained relationships between cancer-related perceived injustice and psycho-spiritual outcomes. Findings support testing acceptance-based interventions to address perceived injustice in advanced cancer patients.

Survival outcomes and toxicity in patients 40 years old or older with relapsed metastatic germ cell tumors treated with high-dose chemotherapy and peripheral blood stem cell transplantation.

BACKGROUND: High-dose chemotherapy (HDCT) plus peripheral blood stem cell transplantation (PBSCT) is effective salvage therapy for relapsed metastatic germ cell tumors (GCTs) but has potential toxicity. Historically, an age of ≥40 years has been associated with greater toxicity and worse outcomes. METHODS: This is a retrospective analysis of 445 consecutive patients with relapsed GCT treated with HDCT and PBSCT with tandem cycles at Indiana University from between 2004-2017 per our institutional regimen. Kaplan-Meier methods and log-rank tests were used for progression-free survival (PFS) and overall survival (OS) analysis. RESULTS: A total of 329 patients were <40 years of age, whereas 116 patients were ≥40 years of age; HDCT was used as second-line therapy in 85% and 79%, respectively. Median follow-up time was 42.5 months (range, 0.3-173.4 months). Grade ≥3 toxicities were similar between either group, except for greater pulmonary (P = .02) and renal toxicity (P = .01) in the ≥40-years-of-age group. Treatment-related mortality was similar between both age groups: 10 patients (3%) in the <40-years-of-age group and 4 patients (3.5%) in ≥40-years-of-age group died from complications of HDCT. Two-year PFS for <40 years of age versus ≥40 years of age was 58.7% versus 59.6% (P = .76) and 2-year OS was 63.9% versus 61.5% (P = .93). Factors predicting worse PFS included Eastern Cooperative Oncology Group performance status ≥1, platinum refractory disease, nonseminoma histology, and not completing 2 cycles of HDCT. Age was not an independent predictor of worse outcomes. CONCLUSIONS: HDCT plus PBSCT is effective salvage therapy in patients ≥40 years of age with relapsed metastatic GCT. Patients ≥40 years of age experience similar rates of toxicity and treatment-related mortality as those <40 years of age.

Phase II trial of brentuximab vedotin in relapsed/refractory germ cell tumors.

Background CD-30 is highly expressed in some patients with non-seminomatous germ-cell tumors. Brentuximab vedotin is an antibody-drug conjugate directed to CD-30. We report a phase 2 trial of brentuximab vedotin in patients with chemo-refractory GCT. Patients and methods This is a single arm, two cohort phase 2 trial investigating brentuximab vedotin 1.8 mg/kg IV every 3 weeks until disease progression or intolerable toxicities in patients with relapsed GCT who have no curative options. Patients with mGCT who progressed after first line cisplatin-based chemotherapy and after at least 1 salvage regimen (high-dose or standard-dose chemotherapy) were eligible. CD30 expression was assessed and two cohorts defined: CD30 positive and CD30 negative/unknown. Results 18 patients were enrolled. Median age 34.7 (range, 23-56). All patients had non-seminoma. Median AFP 4.9 (range, 1-219,345) and hCG 282 (range, 0.6-172,064). Five patients had late relapse (> 2 years). Median number of previous chemotherapy regimens was 3 (range, 2-7). Ten patients received prior high-dose chemotherapy. Seven patients had positive CD30 staining. There were two grade 3 treatment-related adverse events. No partial or complete responses were observed. 6 patients achieved radiographic stable disease (range, 9-14.9 weeks), 5 had elevated AFP or hCG at trial entry and all 5 had transient > 50% decline in baseline AFP/hCG: 4 had CD30 -ve and 2 had CD30 + ve staining; 10 patients had progression of disease as their best response; 2 were not evaluable for response. Conclusion Brentuximab vedotin does not appear to have clinically meaningful single-agent activity in patients with refractory GCT.

Measurement of patients' acceptable symptom levels and priorities for symptom improvement in advanced lung cancer.

PURPOSE: Little research has assessed cancer patients' success criteria and priorities for symptom improvement to inform patient-centered care. Thus, we modified and tested a measure of these constructs for advanced lung cancer patients. We compared acceptable severity levels following symptom treatment across eight symptoms and identified patient subgroups based on symptom importance. METHODS: Advanced lung cancer patients (N=102) completed a one-time survey, including the modified Patient-Centered Outcomes Questionnaire (PCOQ), standard symptom measures, and other clinical characteristics. RESULTS: The modified PCOQ showed evidence of construct validity through associations with theoretically related constructs. Symptom severity and importance were moderately correlated. Levels of acceptable symptom severity were low and did not differ across the eight symptoms. Four patient subgroups were identified: (1) those who rated all symptoms as low in importance (n=12); (2) those who rated bronchial symptoms and sleep problems as low in importance and all other symptoms as moderately important (n=29); (3) those who rated nausea and emotional distress as low in importance and all other symptoms as moderately important (n=23); and (4) those who rated all symptoms as highly important (n=33). Subgroups were unrelated to clinical characteristics, except for functional status. CONCLUSION: The modified PCOQ showed evidence of construct validity. Patients considered low symptom severity to be acceptable, irrespective of the symptom. Findings suggest that symptom severity and importance are related yet distinct aspects of the advanced lung cancer symptom experience. Patients have heterogeneous priorities for symptom improvement, which has implications for tailoring treatment.

Lung Cancer Screening Knowledge Among Internal Medicine Residents in a University Program.

Lung cancer remains the main cause of cancer-related death. Even though several societies recommend that certain populations may benefit from lung cancer screening with low-dose computed tomography (LDCT), its nationwide adoption has been slow. Practices in primary care are closely linked to residency training. Recognizing gaps in knowledge during training may translate into increased utilization of life-saving measures. Sixty internal medicine residents training at a university-based program were presented with an anonymous online-based survey designed to measure their knowledge about lung cancer screening. In the second phase, residents were presented with an infographic containing the answers to the initial survey. They were surveyed again 30 days after this intervention. The average correct response rate among all years was 42%. PGY-1 residents performed better compared with PGY-2 and PGY-3 residents (p = 0.015). Ninety-two percent of residents did not think screening improved all-cause mortality. Less than half thought screening had a lung cancer-specific mortality benefit. Fifty-three percent rated their self-perceived knowledge above 50%. There was no difference in knowledge after the intervention. Specific populations may benefit from LDCT screening. Even if these benefits do not directly translate to population settings, the burden and mortality of lung cancer calls for urgent measures to attempt an earlier diagnosis. Internal medicine residents in this program may have several concerns about lung cancer screening including coverage, benefit, and false positive rate. Educational methods such as infographics may not be effective in improving knowledge among residents. Lung cancer screening should be a priority in medical education, especially in states with high smoking rates and lung cancer mortality.

High-dose chemotherapy plus peripheral blood stem cell transplantation for patients with relapsed germ cell tumors and active brain metastases.

BACKGROUND: The optimal management of progressive brain metastases in patients with germ cell tumors (GCTs) remains unsettled. This study reports the management of 25 consecutive patients with relapsed GCTs and progressive brain metastases undergoing high-dose chemotherapy (HDCT) with peripheral blood stem cell transplantation (PBSCT) at Indiana University from 2006 to 2016. METHODS: All patients were planned to undergo HDCT, which consisted of carboplatin at 700 mg/m2 on days 1 to 3 plus etoposide at 750 mg/m2 on days 1 to 3, followed by PBSCT on day 5 for 2 cycles. Patients were treated with brain metastectomy, stereotactic radiotherapy or whole-brain radiotherapy, HDCT alone, or a combination thereof. All 25 patients had progressive brain metastases at the time of initiating HDCT. Patient and disease characteristics, management of brain metastases, and outcomes were measured. Platelet transfusions were given to maintain platelet counts > 30,000/µL; the goal was >50,000/µL when there were signs of prior or active hemorrhaging. RESULTS: Twenty-two of 25 patients completed both courses of HDCT. The median α-fetoprotein level was 7.5 ng/mL (range, 1.6-1130 ng/mL), and the human chorionic gonadotropin level was 31.3 IU/mL (range, 0.5-25,601 IU/mL). At a median follow-up of 24.5 months (range, 0.4-117 months), 11 patients (44%) were alive with no evidence of disease, 2 patients were alive with relapsed disease, and 12 patients had died of disease progression or complications from HDCT. Fifteen patients developed progressive brain metastases despite radiation and/or craniotomy before HDCT, and 8 of these patients were alive without evidence of disease. There were no intracranial hemorrhagic events leading to death. CONCLUSIONS: Patients with relapsed GCTs and progressive brain metastases are curable with multimodality therapy that includes HDCT and peripheral blood stem cell transplantation.

A phase 2 trial of consolidation pembrolizumab following concurrent chemoradiation for patients with unresectable stage III non-small cell lung cancer: Hoosier Cancer Research Network LUN 14-179.

BACKGROUND: Five-year overall survival (OS) for patients with unresectable stage III non-small cell lung cancer (NSCLC) is poor. Until recently, a standard of care was concurrent chemoradiation alone. Patients with metastatic NSCLC treated with anti-programmed death 1 antibodies have demonstrated improved OS. This trial evaluated pembrolizumab as consolidation therapy after concurrent chemoradiation in patients with unresectable stage III disease. METHODS: Patients with unresectable stage III NSCLC received concurrent chemoradiation with cisplatin and etoposide, cisplatin and pemetrexed, or carboplatin and paclitaxel and 59.4 to 66.6 Gy of radiation. Patients with nonprogression of disease were enrolled and received pembrolizumab (200 mg intravenously every 3 weeks for up to 12 months). The primary endpoint was the time to metastatic disease or death (TMDD). Secondary endpoints included progression-free survival (PFS) and OS. RESULTS: The median follow-up for 93 patients (92 for efficacy) was 32.2 months (range, 1.2-46.6 months). The median TMDD was 30.7 months (95% confidence interval [CI], 18.7 months to not reached), which was significantly longer than the historical control of 12 months (P < .0001). The median PFS was 18.7 months (95% CI, 12.4-33.8 months), and the median OS was 35.8 months (95% CI, 24.2 months to not reached). The 1-, 2-, and 3-year OS estimates were 81.2%, 62.0%, and 48.5%, respectively. Forty patients (43.5%) completed 12 months of treatment (median number of cycles, 13.5). Symptomatic pneumonitis (grade 2 or higher) was noted in 16 patients (17.2%); these cases included 4 grade 3 events (4.3%), 1 grade 4 event (1.1%), and 1 grade 5 event (1.1%). CONCLUSIONS: Consolidation pembrolizumab after concurrent chemoradiation improves TMDD, PFS, and OS in comparison with historical controls of chemoradiation alone. Rates of grade 3 to 5 pneumonitis were similar to those reported with chemoradiation alone.

Computer-Tailored Decision Support Tool for Lung Cancer Screening: Community-Based Pilot Randomized Controlled Trial.

BACKGROUND: Lung cancer screening is a US Preventive Services Task Force Grade B recommendation that has been shown to decrease lung cancer-related mortality by approximately 20%. However, making the decision to screen, or not, for lung cancer is a complex decision because there are potential risks (eg, false positive results, overdiagnosis). Shared decision making was incorporated into the lung cancer screening guideline and, for the first time, is a requirement for reimbursement of a cancer screening test from Medicare. Awareness of lung cancer screening remains low in both the general and screening-eligible populations. When a screening-eligible person visits their clinician never having heard about lung cancer screening, engaging in shared decision making to arrive at an informed decision can be a challenge. Methods to effectively prepare patients for these clinical encounters and support both patients and clinicians to engage in these important discussions are needed. OBJECTIVE: The aim of the study was to estimate the effects of a computer-tailored decision support tool that meets the certification criteria of the International Patient Decision Aid Standards that will prepare individuals and support shared decision making in lung cancer screening decisions. METHODS: A pilot randomized controlled trial with a community-based sample of 60 screening-eligible participants who have never been screened for lung cancer was conducted. Approximately half of the participants (n=31) were randomized to view LungTalk-a web-based tailored computer program-while the other half (n=29) viewed generic information about lung cancer screening from the American Cancer Society. The outcomes that were compared included lung cancer and screening knowledge, lung cancer screening health beliefs (perceived risk, perceived benefits, perceived barriers, and self-efficacy), and perception of being prepared to engage in a discussion about lung cancer screening with their clinician. RESULTS: Knowledge scores increased significantly for both groups with greater improvement noted in the group receiving LungTalk (2.33 vs 1.14 mean change). Perceived self-efficacy and perceived benefits improved in the theoretically expected directions. CONCLUSIONS: LungTalk goes beyond other decision tools by addressing lung health broadly, in the context of performing a low-dose computed tomography of the chest that has the potential to uncover other conditions of concern beyond lung cancer, to more comprehensively educate the individual, and extends the work of nontailored decision aids in the field by introducing tailoring algorithms and message framing based upon smoking status in order to determine what components of the intervention drive behavior change when an individual is informed and makes the decision whether to be screened or not to be screened for lung cancer. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.2196/resprot.8694.

Radiosurgery dose reduction for brain metastases on immunotherapy (RADREMI): A prospective phase I study protocol.

INTRODUCTION: Up to 20% of patients with brain metastases treated with immune checkpoint inhibitor (ICI) therapy and concomitant stereotactic radiosurgery (SRS) suffer from symptomatic radiation necrosis. The goal of this study is to evaluate Radiosurgery Dose Reduction for Brain Metastases on Immunotherapy (RADREMI) on six-month symptomatic radiation necrosis rates. METHODS: This study is a prospective single arm Phase I pilot study which will recruit patients with brain metastases receiving ICI delivered within 30 days before SRS. All patients will be treated with RADREMI dosing, which involves SRS doses of 18 Gy for 0-2 cm lesions, 14 Gy for 2.1-3 cm lesions, and 12 Gy for 3.1-4 cm lesions. All patients will be monitored for six-month symptomatic radiation necrosis (defined as a six-month rate of clinical symptomatology requiring steroid administration and/or operative intervention concomitant with imaging findings consistent with radiation necrosis) and six-month local control. We expect that RADREMI dosing will significantly reduce the symptomatic radiation necrosis rate of concomitant SRS + ICI without significantly sacrificing the local control obtained by the present RTOG 90-05 SRS dosing schema. Local control will be defined according to the Response Assessment in Neuro-Oncology (RANO) criteria. DISCUSSION: This study is the first prospective trial to investigate the safety of dose-reduced SRS in treatment of brain metastases with concomitant ICI. The findings should provide fertile soil for future multi-institutional collaborative efficacy trials of RADREMI dosing for this patient population. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT04047602 (registration date: July 25, 2019).

Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration Use for Subclassification and Genotyping of Lung Non-Small-Cell Carcinoma.

OBJECTIVES: Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is the primary method for the diagnosis and staging of lung cancer. The purpose of this study was to assess the yield of EBUS-TBNA in the subtyping and genotyping of lung adenocarcinoma. METHODS: Sixty-nine patients at Indiana University Hospital and Sidney and Lois Eskenazi Hospital with possible or confirmed lung adenocarcinoma underwent EBUS-TBNA using a 21-gauge Olympus needle without suction. Samples were sent for molecular testing after rapid onsite specimen evaluation. A total of 6 to 10 passes were placed in a cell block. RESULTS: Sixty-nine samples from patients with non-small-cell lung cancer were sent for molecular testing for epidermal growth factor receptor. Results were obtained in all of the patients. Mutations were found in three patients (4.3%). Fifty-eight samples were sent for V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (100% yield), 10 of which had mutations (17.2%). Fifty-one samples were sent for proto-oncogene tyrosine-protein kinase ROS testing (1 [7.8%] mutant). Tissue samples were inadequate in three patients (94.1% yield). Sixty-three samples were sent for anaplastic lymphoma receptor tyrosine kinase testing (3 [4.8%] mutant, 6 [9.5%] inadequate, 90.5% yield). CONCLUSIONS: EBUS-TBNA with a 21-gauge needle is appropriate for the analysis of multiple mutations and the genotyping of lung adenocarcinoma.

A randomized, double-blind, phase 2 trial of platinum therapy plus etoposide with or without concurrent vandetanib (ZD6474) in patients with previously untreated extensive-stage small cell lung cancer: Hoosier Cancer Research Network LUN06-113.

BACKGROUND: This randomized, double-blind, phase 2 trial evaluated whether the addition of vandetanib to platinum plus etoposide for previously untreated extensive-stage small cell lung cancer (SCLC) prolonged the time to disease progression in comparison with chemotherapy alone. METHODS: Patients with previously untreated extensive-stage SCLC received platinum (cisplatin or carboplatin) with etoposide in combination with vandetanib (100 mg daily) or a placebo for up to 4 total cycles (no maintenance therapy). An initial safety run-in phase was conducted with the first 6 patients enrolled; all these patients received vandetanib with cisplatin and etoposide. With an overall sample size of 68 patients, the study had 80% power to detect a 3-month difference in the time to progression (TTP) from 4 to 7 months (significance level,.10 [1-sided log-rank test]). RESULTS: Seventy-four patients were enrolled between April 2008 and May 2013. Thirty-three patients were ultimately randomized to each arm. The baseline characteristics were well balanced, and the median number of treatment cycles was 4 for each arm. Thirty-one patients in each arm were evaluable for TTP; the median TTP was 5.62 months with vandetanib and 5.68 months with the placebo (P = .9518). The median overall survival was 13.24 months with vandetanib and 9.23 months with the placebo (P = .4577; 33 evaluable patients in each arm). Nonhematologic toxicity was increased with vandetanib versus the placebo. No correlation was seen between vascular endothelial growth factor polymorphisms and outcomes. CONCLUSIONS: The addition of vandetanib to platinum and etoposide did not improve outcomes for patients with newly diagnosed extensive-stage SCLC. Toxicity was increased in comparison with chemotherapy alone. Cancer 2017;123:303-311. © 2016 American Cancer Society.

Lung cancer screening: what do long-term smokers know and believe?

OBJECTIVE: To explore knowledge and beliefs of long-term smokers about lung cancer, associated risk factors and lung cancer screening. DESIGN: Qualitative study theoretically framed by the expanded Health Belief Model based on four focus group discussions. Content analysis was performed to identify themes of knowledge and beliefs about lung cancer, associated risk factors and lung cancer screening among long-term smokers' who had and had not been screened for lung cancer. METHODS: Twenty-six long-term smokers were recruited; two groups (n = 9; n = 3) had recently been screened and two groups (n = 7; n = 7) had never been screened. RESULTS: While most agreed lung cancer is deadly, confusion or inaccurate information exists regarding the causes and associated risk factors. Knowledge related to lung cancer screening and how it is performed was low; awareness of long-term smoking's association with lung cancer risk remains suboptimal. Perceived benefits of screening identified include: (i) finding lung cancer early; (ii) giving peace of mind; and (iii) motivation to quit smoking. Perceived barriers to screening identified include: (i) inconvenience; (ii) distrust; and (iii) stigma. CONCLUSIONS: Perceived barriers to lung cancer screening, such as distrust and stigma, must be addressed as lung cancer screening becomes more widely implemented. Heightened levels of health-care system distrust may impact successful implementation of screening programmes. Perceived smoking-related stigma may lead to low levels of patient engagement with medical care and decreased cancer screening participation. It is also important to determine modifiable targets for intervention to enhance the shared decision-making process between health-care providers and their high-risk patients.

Phase II study of fosaprepitant + 5HT3 receptor antagonist + dexamethasone in patients with germ cell tumors undergoing 5-day cisplatin-based chemotherapy: a Hoosier Cancer Research Network study.

PURPOSE: A phase III study adding aprepitant to a 5HT3 receptor antagonist (5HT3-RA) plus dexamethasone in germ cell tumor (GCT) patients treated with 5-day cisplatin combination chemotherapy demonstrated a significant improvement in complete response (CR) (J Clin Onc 30:3998-4003, 2012). Fosaprepitant has demonstrated non-inferiority compared to aprepitant in single-day cisplatin chemotherapy and is approved as a single-dose alternative. This single-arm phase II study is the first clinical trial evaluating fosaprepitant in patients receiving multi-day cisplatin regimen. METHODS: GCT patients receiving a 5-day cisplatin combination chemotherapy were enrolled. Fosaprepitant 150 mg was given IV on days 3 and 5. A 5HT3-RA days 1-5 (days 1, 3, and 5, if palonosetron) plus dexamethasone 20 mg days 1 and 2 and 4 mg po bid days 6, 7, and 8 was administered. Rescue antiemetics were allowed. The primary objective was to determine the CR rate-no emetic episodes or use of rescue medications. Accrual of 64 patients was planned with expected CR > 27 %. RESULTS: Sixty-five patients were enrolled of whom 54 were eligible for analysis. Median age was 33. Fifty-one patients received bleomycin, etoposide, and cisplatin (BEP) chemotherapy. CR was observed in 13 (24.1 %) patients (95 % Agresti-Coull binomial C.I. 14.5 %, 37.1 %). CONCLUSION: The data in this phase II study, in contrast to our prior phase III study, appears to indicate a lower CR rate with the substitution of fosaprepitant for aprepitant. It is unknown whether the substitution of fosaprepitant for aprepitant provides the same benefit in multi-day cisplatin that was achieved with single-day cisplatin. Trial registration Clinical trial information NCT01736917.

Three-arm, randomized, phase 2 study of carboplatin and paclitaxel in combination with cetuximab, cixutumumab, or both for advanced non-small cell lung cancer (NSCLC) patients who will not receive bevacizumab-based therapy: An Eastern Cooperative Oncology Group (ECOG) study (E4508).

BACKGROUND: Preclinical evidence supports the clinical investigation of inhibitors to the insulin-like growth factor receptor (IGFR) and the epidermal growth factor receptor (EGFR) either alone or in combination as treatment for patients with non-small cell lung cancer (NSCLC). METHODS: Patients with chemotherapy-naïve, advanced NSCLC who had an Eastern Cooperative Oncology Group performance status of 0 or 1 were eligible. Patients were randomized to receive carboplatin intravenously at an area under the plasma drug concentration-time curve of 6.0 plus paclitaxel 200 mg/m(2) intravenously on day 1 every 3 weeks combined with either intravenous cetuximab weekly (arm A), intravenous cixutumumab every 2 weeks (arm B), or both (arm C). Patients who had nonprogessing disease after 12 weeks of therapy were permitted to continue on maintenance antibody therapy until they developed progressive disease. The primary endpoint was progression-free survival (PFS). The study design required 180 eligible patients and had 88% power to detect a 60% increase in median PFS for either comparison (arm A vs arm C or arm B vs arm C) using the log-rank test. RESULTS: From September 2009 to December 2010, 140 patients were accrued. The study was closed to accrual early because of an excessive number of grade 5 events reported on arms A and C. Thirteen patients died during treatment (6 patients on arm A, 2 patients on arm B, and 5 patients on arm C), including 9 within approximately 1 month of starting therapy. The estimated median PFS for arms A, B, and C were similar at 3.4 months, 4.2 months, and 4 months, respectively. CONCLUSIONS: On the basis of the apparent lack of efficacy and excessive premature deaths, the current results do not support the continued investigation of carboplatin, paclitaxel, and cixutumumab either alone or in combination with cetuximab for patients with advanced NSCLC.

Locally Advanced Non-Small Cell Lung Cancer: Optimal Chemotherapeutic Agents and Duration.

OPINION STATEMENT: Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related mortality in the USA. The treatment of locally advanced NSCLC (LA-NSCLC) is challenging and must be individualized. For patients with completely resected stage III NSCLC, adjuvant cisplatin-based chemotherapy for 4 cycles is recommended. For patients with inoperable or unresectable stage III NSCLC, chemoradiation is the preferred treatment. Patients with a good performance status, minimal or no weight loss, and adequate pulmonary function should be offered concurrent chemoradiation. The optimal chemotherapeutic agents to be used concurrently with radiation remain undefined. In the USA, cisplatin plus etoposide or carboplatin plus paclitaxel are the most commonly used regimens. In addition, the optimal duration of therapy remains undefined, including the role of consolidation chemotherapy. Thus far, randomized phase III trials have failed to identify a survival advantage for administering chemotherapy beyond that delivered during radiation therapy. Molecularly targeted agents, angiogenesis inhibitors, and immunotherapy have a defined role for patients with metastatic disease. The role, if any, of these new classes of agents is undergoing investigation for patients with earlier stage disease, including stage III disease.