Weekly nab-Paclitaxel in Combination With Carboplatin Versus Solvent-Based Paclitaxel Plus Carboplatin as First-Line Therapy in Patients With Advanced Non–Small-Cell Lung Cancer: Final Results of a Phase III Trial Mark A. Socinski, Igor Bondarenko, Nina A. Karaseva, Anatoly M. Makhson, Igor Vynnychenko, Isamu Okamoto, Jeremy K. Hon, Vera Hirsh, Paul Bhar, Hui Zhang, Jose L. Iglesias, and Markus F. Renschler See accompanying editorial on page 2025 and articles on pages 2046 and 2063 Mark A. Socinski, Lineberger Compre- hensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC; Igor Bondarenko, City Hospital #4, Dnepropetrovsk; Igor Vynnychenko, Regional Oncology Center, Sumy, Ukraine; Nina A. Karaseva, City Oncol- ogy Center, St. Petersburg; Anatoly M. Makhson, City Oncology Hospital #62, Moscow, Russia; Isamu Okamoto, Kinki University Faculty of Medicine, Osaka- Sayama, Japan; Jeremy K. Hon, Clear- view Cancer Institute, Huntsville, AL; Vera Hirsh, McGill University, Montreal, Quebec, Canada; Paul Bhar, Hui Zhang, Jose L. Iglesias, and Markus F. Renschler, Celgene, Summit, NJ. Submitted September 20, 2011; accepted February 22, 2012; published online ahead of print at www.jco.org on April 30, 2012. Supported by Celgene, Summit, NJ. Presented at the 46th Annual Meeting of the American Society of Clinical Oncology (ASCO), Chicago, IL, June 4-8, 2010; the 47th Annual Meeting of ASCO, Chicago, IL, June 2-7, 2011, and 14th World Conference on Lung Cancer, Amsterdam Rai, the Nether- lands, July 3-7, 2011. Authors’ disclosures of potential con- flicts of interest and author contribu- tions are found at the end of this article. Clinical Trials repository link available on JCO.org Corresponding author: Mark A. Socin- ski, MD, University of Pittsburgh Medi- cal Center, Cancer Pavilion, 5150 Centre Ave, Fifth Floor, Pittsburgh, PA 15232; e-mail: socinskima@upmc.edu. © 2012 by American Society of Clinical Oncology 0732-183X/12/3017-2055/$20.00 DOI: 10.1200/JCO.2011.39.5848 A B S T R A C T Purpose This phase III trial compared the efficacy and safety of albumin-bound paclitaxel (nab-paclitaxel) plus carboplatin with solvent-based paclitaxel (sb-paclitaxel) plus carboplatin in advanced non– small-cell lung cancer (NSCLC). Patients and Methods In all, 1,052 untreated patients with stage IIIB to IV NSCLC were randomly assigned 1:1 to receive 100 mg/m 2 nab-paclitaxel weekly and carboplatin at area under the concentration-time curve (AUC) 6 once every 3 weeks (nab-PC) or 200 mg/m 2 sb-paclitaxel plus carboplatin AUC 6 once every 3 weeks (sb-PC). The primary end point was objective overall response rate (ORR). Results On the basis of independent assessment, nab-PC demonstrated a significantly higher ORR than sb-PC (33% v 25%; response rate ratio, 1.313; 95% CI, 1.082 to 1.593; P = .005) and in patients with squamous histology (41% v 24%; response rate ratio, 1.680; 95% CI, 1.271 to 2.221; P  .001). nab-PC was as effective as sb-PC in patients with nonsquamous histology (ORR, 26% v 25%; P = .808). There was an approximately 10% improvement in progression-free survival (median, 6.3 v 5.8 months; hazard ratio [HR], 0.902; 95% CI, 0.767 to 1.060; P = .214) and overall survival (OS; median, 12.1 v 11.2 months; HR, 0.922; 95% CI, 0.797 to 1.066; P = .271) in the nab-PC arm versus the sb-PC arm, respectively. Patients  70 years old and those enrolled in North America showed a significantly increased OS with nab-PC versus sb-PC. Significantly less grade  3 neuropathy, neutropenia, arthralgia, and myalgia occurred in the nab-PC arm, and less thrombocytopenia and anemia occurred in the sb-PC arm. Conclusion The administration of nab-PC as first-line therapy in patients with advanced NSCLC was efficacious and resulted in a significantly improved ORR versus sb-PC, achieving the primary end point. nab-PC produced less neuropathy than sb-PC. J Clin Oncol 30:2055-2062. © 2012 by American Society of Clinical Oncology INTRODUCTION Non–small-cell lung cancer (NSCLC) is the leading cause of cancer death, with only 1% 5-year survival for stage IV NSCLC. 1,2 The current standard of care in advanced NSCLC is a platinum agent com- bined with a third-generation therapeutic, most commonly taxanes, gemcitabine, vinorelbine, or pemetrexed. 1-3 However, therapy with platinum- based doublets has reached a therapeutic plateau. In a large randomized study (N = 1,155) comparing four platinum-based regimens, none of them of- fered a significant clinical advantage over the others, with an overall response rate (ORR) of 19% and a median overall survival (OS) of 7.9 months for all patients. 4 Similarly, a phase III study in patients with advanced NSCLC treated with cisplatin plus pem- etrexed showed no improvement in tumor response rate and survival over cisplatin plus gemcitabine for all histologies; however, an improvement in survival was noted in the nonsquamous histology subset with a decrement in the squamous histology sub- set. 5,6 In general, solvent-based paclitaxel (sb- paclitaxel) plus carboplatin, the most commonly JOURNAL OF CLINICAL ONCOLOGY O R I G I N A L R E P O R T VOLUME 30  NUMBER 17  JUNE 10 2012 © 2012 by American Society of Clinical Oncology 2055 Downloaded from ascopubs.org by 44.200.81.239 on June 6, 2022 from 044.200.081.239 Copyright © 2022 American Society of Clinical Oncology. 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