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A randomised phase II clinical trial of nab-paclitaxel and carboplatin compared with gemcitabine and carboplatin as first-line therapy in advanced squamous cell lung carcinoma (C-TONG1002)

Published:February 07, 2019DOI:https://doi.org/10.1016/j.ejca.2019.01.007

      Highlights

      • Nab-paclitaxel/carboplatin and gemcitabine/carboplatin had the same efficacy in advanced squamous cell lung carcinoma.
      • Both progression-free survival and overall survival had no difference between the two arms.
      • Both nab-PC and GC are well tolerated.
      • Nab-PC had advantage of improving quality of life.

      Abstract

      Background

      Nab-paclitaxel/carboplatin (nab-PC) and gemcitabine/carboplatin (GC) are the standard first-line chemotherapy in non–small cell lung carcinoma. Up to now, there is no head to head trial to compare nab-PC with GC in advanced squamous cell lung carcinoma.

      Patients and methods

      A multicentre randomised phase II trial was performed to compare the efficacy and safety for nab-PC with GC in previously untreated patients with advanced squamous cell lung carcinoma. The primary end-point was objective response rate (ORR). Progression-free survival (PFS), overall survival (OS), treatment-related adverse events and quality of life (QoL) were also analysed.

      Results

      Totally 127 participants were eligible for this study (62/65 nab-PC/GC). Nab-PC has higher ORR than GC without statistical significance (42% versus 27%, P > 0.05). After a median follow-up of 14.5 months, both PFS and OS had no difference between the two arms (6.7 versus 5.8 months, hazard ratio [HR] 0.75, P = 0.143; 11.6 versus 14.4 months, HR 0.92, P = 0.846). Both regimens were well tolerated; however, more dose reduction occurred after cycle 2 in GC (27%) than in nab-PC (12%) (P < 0.05). Significant QoL improvement measured by trial outcome index was seen in nab-PC than in GC (P < 0.05).

      Conclusions

      The first-line nab-PC and GC had the same response, PFS, and OS in patients with advanced squamous cell lung carcinoma. Nab-PCM has advantage over GC in QoL improvement.

      Trial registration number

      NCT01236716.

      Keywords

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      References

        • Reck M.
        • Rodriguez-Abreu D.
        • Robinson A.G.
        • Hui R.
        • Csoszi T.
        • Fulop A.
        • et al.
        Pembrolizumab versus chemotherapy for PD-L1-positive non-small-cell lung cancer.
        N Engl J Med. 2016; 375: 1823-1833
        • Gandhi L.
        • Rodriguez-Abreu D.
        • Gadgeel S.
        • Esteban E.
        • Felip E.
        • De Angelis F.
        • et al.
        Pembrolizumab plus chemotherapy in metastatic non-small-cell lung cancer.
        N Engl J Med. 2018; 378: 2078-2092
        • Jotte R.M.
        • Cappuzzo F.
        • Vynnychenko I.
        • Stroyakovsky D.L.
        • Abreu D.R.
        • Hussein M.A.
        • et al.
        IMpower131: primary PFS and safety analysis of a randomized phase III study of atezolizumab + carboplatin + paclitaxel or nab-paclitaxel vs carboplatin + nab-paclitaxel as 1L therapy in advanced squamous NSCLC.
        J Clin Oncol. 2018; 36 (abstr LBA9000)
        • Paz-Ares L.
        • Luft A.
        • Vicente D.
        • Tafreshi A.
        • Gumus M.
        • Mazieres J.
        • et al.
        Pembrolizumab plus chemotherapy for squamous non-small-cell lung cancer.
        N Engl J Med. 2018; 379: 2040-2051
        • Sandler A.
        • Gray R.
        • Perry M.C.
        • Brahmer J.
        • Schiller J.H.
        • Dowlati A.
        • et al.
        Paclitaxel-carboplatin alone or with bevacizumab for non-small-cell lung cancer.
        N Engl J Med. 2006; 355: 2542-2550
        • Zhou C.
        • Wu Y.L.
        • Chen G.
        • Liu X.
        • Zhu Y.
        • Lu S.
        • et al.
        BEYOND: a randomized, double-blind, placebo-controlled, multicenter, phase III study of first-line carboplatin/paclitaxel plus bevacizumab or placebo in Chinese patients with advanced or recurrent nonsquamous non-small-cell lung cancer.
        J Clin Oncol. 2015; 33: 2197-2204
        • Socinski M.A.
        • Bondarenko I.
        • Karaseva N.A.
        • Makhson A.M.
        • Vynnychenko I.
        • Okamoto I.
        • et al.
        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.
        J Clin Oncol. 2012; 30: 2055-2062
        • Socinski M.A.
        • Langer C.J.
        • Okamoto I.
        • Hon J.K.
        • Hirsh V.
        • Dakhil S.R.
        • et al.
        Safety and efficacy of weekly nab(R)-paclitaxel in combination with carboplatin as first-line therapy in elderly patients with advanced non-small-cell lung cancer.
        Ann Oncol. 2013; 24: 314-321
        • Thatcher N.
        • Hirsch F.R.
        • Luft A.V.
        • Szczesna A.
        • Ciuleanu T.E.
        • Dediu M.
        • et al.
        Necitumumab plus gemcitabine and cisplatin versus gemcitabine and cisplatin alone as first-line therapy in patients with stage IV squamous non-small-cell lung cancer (SQUIRE): an open-label, randomised, controlled phase 3 trial.
        Lancet Oncol. 2015; 16: 763-774
        • Eisenhauer E.A.
        • Therasse P.
        • Bogaerts J.
        • Schwartz L.H.
        • Sargent D.
        • Ford R.
        • et al.
        New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1).
        Eur J Cancer. 2009; 45: 228-247
        • Cella D.
        • Eton D.T.
        • Fairclough D.L.
        • Bonomi P.
        • Heyes A.E.
        • Silberman C.
        • et al.
        What is a clinically meaningful change on the functional assessment of cancer therapy-lung (FACT-L) questionnaire? Results from Eastern Cooperative Oncology Group (ECOG) study 5592.
        J Clin Epidemiol. 2002; 55: 285-295
        • Schiller J.H.
        • Harrington D.
        • Belani C.P.
        • Langer C.
        • Sandler A.
        • Krook J.
        • et al.
        Comparison of four chemotherapy regimens for advanced non-small-cell lung cancer.
        N Engl J Med. 2002; 346: 92-98
        • Cella D.F.
        • Bonomi A.E.
        • Lloyd S.R.
        • Tulsky D.S.
        • Kaplan E.
        • Bonomi P.
        Reliability and validity of the functional assessment of cancer therapy-lung (FACT-L) quality of life instrument.
        Lung Cancer. 1995; 12: 199-220
        • Lee H.
        • Jeong S.H.
        • Jeong B.H.
        • Park H.Y.
        • Lee K.J.
        • Um S.W.
        • et al.
        Incidence of brain metastasis at the initial diagnosis of lung squamous cell carcinoma on the basis of stage, excluding brain metastasis.
        J Thorac Oncol. 2016; 11: 426-431
        • Mujoomdar A.
        • Austin J.H.
        • Malhotra R.
        • Powell C.A.
        • Pearson G.D.
        • Shiau M.C.
        • et al.
        Clinical predictors of metastatic disease to the brain from non-small cell lung carcinoma: primary tumor size, cell type, and lymph node metastases.
        Radiology. 2007; 242: 882-888
        • Weiss G.J.
        • Waypa J.
        • Blaydorn L.
        • Coats J.
        • McGahey K.
        • Sangal A.
        • et al.
        A phase Ib study of pembrolizumab plus chemotherapy in patients with advanced cancer (PembroPlus).
        Br J Cancer. 2017; 117: 33-40
        • Frese K.K.
        • Neesse A.
        • Cook N.
        • Bapiro T.E.
        • Lolkema M.P.
        • Jodrell D.I.
        • et al.
        nab-Paclitaxel potentiates gemcitabine activity by reducing cytidine deaminase levels in a mouse model of pancreatic cancer.
        Cancer Discov. 2012; 2: 260-269
        • Paul K.P.
        • Aparajita S.
        • Linda Su Hyun A.
        • Andrew J.P.
        • Kenneth K.N.
        • Daniel M.
        • et al.
        A phase II trial of albumin-bound paclitaxel and gemcitabine in patients with newly diagnosed PD-L1 IHC low/unknown stage IV squamous cell lung cancers.
        J Clin Oncol. 2018; 36e21035
        • de Castria T.B.
        • da Silva E.M.
        • Gois A.F.
        • Riera R.
        Cisplatin versus carboplatin in combination with third-generation drugs for advanced non-small cell lung cancer.
        Cochrane Database Syst Rev. 2013; CD009256