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Nab-Paclitaxel-Based Therapy in Underserved Patient Populations: The ABOUND.70+ Study in Elderly Patients With Advanced NSCLC.

ABSTRACT: The phase 4 ABOUND.70+ trial assessed the safety and efficacy of nab-paclitaxel/carboplatin continuously or with a 1-week break between cycles in elderly patients with advanced non-small cell lung cancer (NSCLC). Patients ?70?years with locally advanced/metastatic NSCLC were randomized 1:1 to first-line nab-paclitaxel days 1, 8, 15 plus carboplatin day 1 of a 21-day cycle (21d) or the same nab-paclitaxel/carboplatin regimen with a 1-week break between cycles (21d?+?break; 28d). The primary endpoint was the percentage of patients with grade???2 peripheral neuropathy (PN) or grade???3 myelosuppression. Other key endpoints included progression-free survival (PFS), overall survival (OS), and overall response rate (ORR). A total of 143 patients were randomized (71 to 21d, 72 to 21d?+?break). The percentage of patients with grade???2 PN or grade???3 myelosuppression was similar between the 21d and 21d?+?break arms (76.5 and 77.1%; P?=?0.9258). Treatment exposure was lower in the 21d arm compared with the 21d?+?break arm. Median OS was 15.2 and 16.2?months [hazard ratio (HR) 0.72, 95% CI 0.44-1.19; P?=?0.1966], median PFS was 3.6 and 7.0?months (HR 0.48, 95% CI 0.30-0.76; P?

SUBMITTER: Langer CJ

PROVIDER: S-EPMC6066531 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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nab-Paclitaxel-Based Therapy in Underserved Patient Populations: The ABOUND.70+ Study in Elderly Patients With Advanced NSCLC.

Langer Corey J CJ Kim Edward S ES Anderson Eric C EC Jotte Robert M RM Modiano Manuel M Haggstrom Daniel E DE Socoteanu Matei P MP Smith David A DA Dakhil Christopher C Konduri Kartik K Berry Tymara T Ong Teng J TJ Sanford Alexandra A Amiri Katayoun K Goldman Jonathan W JW Weiss Jared J

Frontiers in oncology 20180724

The phase 4 ABOUND.70+ trial assessed the safety and efficacy of nab-paclitaxel/carboplatin continuously or with a 1-week break between cycles in elderly patients with advanced non-small cell lung cancer (NSCLC). Patients ≥70 years with locally advanced/metastatic NSCLC were randomized 1:1 to first-line nab-paclitaxel days 1, 8, 15 plus carboplatin day 1 of a 21-day cycle (21d) or the same nab-paclitaxel/carboplatin regimen with a 1-week break between cycles (21d + break; 28 ...[more]

PMID: 30087851

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Project description:IntroductionDespite improvements in the treatment of advanced non-small cell lung cancer (NSCLC), certain patient populations remain underrepresented in clinical trials. Many patients have benefited from platinum doublets, including nab-paclitaxel-based regimens, but there are patients with comorbidities who particularly require careful balancing of efficacy and safety. Clinical trial data are limited for patients who are elderly or have renal impairment, diabetes, or impaired performance status.MethodsTo better understand outcomes in these patient populations, we performed a pooled analysis using data from the ABOUND clinical trial program (ABOUND.SQM, ABOUND.PS2, ABOUND.70+) and the key phase III trial of nab-paclitaxel/carboplatin in advanced NSCLC. The populations included in this pooled analysis consisted of elderly patients (≥ 70 years) and patients with renal impairment (eGFR < 60 ml/min/1.73 m2), diabetes, or poor performance status (ECOG PS 2).ResultsMedian progression-free survival (PFS) ranged from 4.1 months in patients with ECOG PS 2 (95% CI, 2.04-5.09 months) to 7.7 months in patients with diabetes (95% CI, 5.88-10.12 months). PFS for elderly patients and patients with renal impairment was 6.9 months each (95% CI, 6.01-7.98 months and 4.47-9.79 months, respectively). Median overall survival (OS) was 18.2 months (95% CI, 10.94-28.22 months), 17.4 months (95% CI, 14.59-20.14 months), and 16.1 months (95% CI, 14.09-18.50 months) in patients with renal impairment, patients with diabetes, and elderly patients, respectively. Patients with ECOG PS 2 exhibited the shortest median OS: 5.6 months (95% CI, 3.98-11.37 months). Overall response rates were 56.9%, 54.6%, 45.9%, and 29.4% in patients with diabetes, elderly patients, patients with renal impairment, and patients with ECOG PS 2, respectively. Most treatment-related adverse events were hematologic. The most common grade 3/4 hematologic adverse events in patients with renal impairment, elderly patients, patients with diabetes, and patients with poor performance status included neutropenia, anemia, and thrombocytopenia.ConclusionsAlthough survival data in patients with ECOG PS 2 were notably inferior to the other cohorts, our findings are consistent with those previously reported in the population-specific studies of the ABOUND trials and lend additional support for the use of nab-paclitaxel-based regimens in historically understudied and vulnerable populations.

Project description:BACKGROUND:Previous trials have suggested that elderly patients with non-small-cell lung cancer (NSCLC) could benefit from nanoparticle albumin-bound paclitaxel (nab-paclitaxel). Real-world data on the elderly Chinese population are lacking. This study aimed to analyze the effectiveness and tolerability of nab-paclitaxel in Chinese elderly patients (?65?years) with advanced NSCLC. METHODS:This study included 76 patients with a primary diagnosis of IIIB-IV NSCLC from January 2010 to December 2017 at Peking University Cancer Hospital, who received nab-paclitaxel (125 or 130?mg/m2 i.v.) every three?weeks. The overall survival (OS), progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and adverse events (AEs) were analyzed. RESULTS:There were 12 patients who received nab-paclitaxel as the first-line treatment (seven also received carboplatin), and 64 received nab-paclitaxel as the latter-line treatment. The overall ORR, DCR, median PFS, and median OS were 14.5%, 69.7%, 5.2?months, and 12.2?months, respectively. The Eastern Cooperative Oncology Group performance status of one and the age of 70-74?years were independently associated with longer OS, while early treatment line of nab-paclitaxel and age of 70-74?years were independently associated with longer PFS. The most common AEs were anemia, leukopenia, gastrointestinal reaction, fatigue, and peripheral neuropathy, which were all manageable. Dose adjustment or treatment discontinuation was encountered in 10 patients because of AEs. The incidence of AEs was not different among age subgroups. CONCLUSIONS:Nab-paclitaxel has a good clinical response profile in Chinese elderly patients with stage IIIB-IV NSCLC. Prospective clinical trials are needed to confirm these results. KEY POINTS:Significant findings of the study Nanoparticle albumin-bound paclitaxel (nab-paclitaxel) has a good clinical response profile in Chinese elderly (?65?years) patients with stage IIIB-IV non-small-cell lung cancer (NSCLC), with acceptable and manageable adverse events. What this study adds Preliminary evidence shows a good clinical response from treatment with nab-paclitaxel in Chinese elderly patients with advanced NSCLC.

Project description:UnlabelledIn this phase II trial, carboplatin with nanoparticle albumin-bound (nab)-paclitaxel as first-line therapy for advanced non-small-cell lung cancer (NSCLC) was evaluated. Most patients had squamous cell histology. Tumor-associated stromal caveolin-1 (Cav-1) expression was correlated with improved response rate and survival in NSCLC patients who received nab-paclitaxel in this phase II trial. These results suggest Cav-1 might serve as a potential biomarker in this patient population.BackgroundThe combination of bevacizumab with platinum-based chemotherapy results in greater response rate (RR) and overall survival (OS) in advanced non-small-cell lung cancer (NSCLC). Bevacizumab is contraindicated in patients with squamous histology or hemoptysis. Nanoparticle albumin-bound (nab)-paclitaxel is a novel formulation of paclitaxel with greater dose tolerance and improved efficacy. We hypothesized that nab-paclitaxel and carboplatin would be superior to alternative doublets in advanced NSCLC patients ineligible for bevacizumab.Patients and methodsWe conducted a single-arm phase II trial (NCT00729612) with carboplatin and nab-paclitaxel on day 1 of a 21-day cycle to evaluate RR (primary end point), safety, toxicity, and OS. Eligibility included: squamous histology, hemoptysis, or ongoing anticoagulation. Correlative studies included immunohistochemistry for secreted protein acid rich in cysteine (SPARC) and caveolin-1 (Cav-1).ResultsSixty-three patients were enrolled. Most patients had squamous cell carcinoma (n = 48); other reasons for eligibility included hemoptysis (n = 11) and anticoagulation (n = 2). Toxicity Grade ≥ 3/4 included neuropathy, cytopenias, and fatigue. RR was 38% (24 partial response/0 complete response); 20 patients had stable disease (32%). Median progression-free survival was 5 months and median OS was 9.7 months. Immunohistochemistry for SPARC and Cav-1 was performed in 38 and 37 patients respectively. Although no association was found for SPARC expression in tumor or stroma with RR or OS, we found that higher Cav-1 levels in tumor-associated stroma was associated with improved RR and OS.ConclusionCarboplatin and nab-paclitaxel every 21 days demonstrated promising efficacy with tolerable toxicity in NSCLC patients ineligible for bevacizumab therapy. Further analysis and validation of Cav-1 and SPARC expression in tumor and stromal compartments as prognostic and/or predictive biomarkers of NSCLC or nab-paclitaxel treatment is warranted.

Dataset Information

Nab-Paclitaxel-Based Therapy in Underserved Patient Populations: The ABOUND.70+ Study in Elderly Patients With Advanced NSCLC.

Publications

<i>nab</i>-Paclitaxel-Based Therapy in Underserved Patient Populations: The ABOUND.70+ Study in Elderly Patients With Advanced NSCLC.

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