Phase III study of carboplatin and paclitaxel alone or with sorafenib in advanced non-small-cell lung cancer

Giorgio Scagliotti, Silvia Novello, Joachim Von Pawel, Martin Reck, José Rodrigues Pereira, Michael Thomas, José Elias Abrão Miziara, Beatrix Balint, Filippo De Marinis, Alan Keller, Osvaldo Arén, Maria Csollak, Istvan Albert, Carlos Henrique Barrios, Francesco Grossi, Maciej Krzakowski, Lisa Cupit, Frank Cihon, Sandra DiMatteo, Nasser Hanna

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Abstract

Purpose: This phase III, multicenter, randomized, placebo-controlled trial assessed the efficacy and safety of sorafenib, an oral multikinase inhibitor, in combination with carboplatin and paclitaxel in chemotherapy-naïve patients with unresectable stage IIIB or IV non-small-cell lung cancer (NSCLC). Patients and Methods: Nine hundred twenty-six patients were randomly assigned to receive up to six 21-day cycles of carboplatin area under the curve 6 and paclitaxel 200 mg/m2 (CP) on day 1, followed by either sorafenib 400 mg twice a day (n = 464, arm A) or placebo (n = 462, arm B) on days 2 to 19. The maintenance phase after CP consisted of sorafenib 400 mg or placebo twice a day. The primary end point was overall survival (OS); secondary end points included progression-free survival and tumor response. Results: Overall demographics were balanced between arms; 223 patients (24%) had squamous cell histology. On the basis of a planned interim analysis, median OS was 10.7 months in arm A and 10.6 months in arm B (hazard ratio [HR] = 1.15; 95% CI, 0.94 to 1.41; P = .915). The study was terminated after the interim analysis concluded that the study was highly unlikely to meet its primary end point. A prespecified exploratory analysis revealed that patients with squamous cell histology had greater mortality in arm A than in arm B (HR = 1.85; 95% CI, 1.22 to 2.81). Main grade 3 or 4 sorafenib-related toxicities included rash (8.4%), hand-foot skin reaction (7.8%), and diarrhea (3.5%). Conclusion: No clinical benefit was observed from adding sorafenib to CP chemotherapy as first-line treatment for NSCLC.

Original languageEnglish
Pages (from-to)1835-1842
Number of pages8
JournalJournal of Clinical Oncology
Volume28
Issue number11
DOIs
StatePublished - Apr 10 2010
Externally publishedYes

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Carboplatin
Paclitaxel
Non-Small Cell Lung Carcinoma
Arm
Placebos
Histology
Epithelial Cells
Drug Therapy
Survival
sorafenib
Exanthema
Disease-Free Survival
Area Under Curve
Foot
Diarrhea
Randomized Controlled Trials
Hand
Maintenance
Demography
Safety

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Medicine(all)

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Phase III study of carboplatin and paclitaxel alone or with sorafenib in advanced non-small-cell lung cancer. / Scagliotti, Giorgio; Novello, Silvia; Von Pawel, Joachim; Reck, Martin; Pereira, José Rodrigues; Thomas, Michael; Miziara, José Elias Abrão; Balint, Beatrix; De Marinis, Filippo; Keller, Alan; Arén, Osvaldo; Csollak, Maria; Albert, Istvan; Barrios, Carlos Henrique; Grossi, Francesco; Krzakowski, Maciej; Cupit, Lisa; Cihon, Frank; DiMatteo, Sandra; Hanna, Nasser.

In: Journal of Clinical Oncology, Vol. 28, No. 11, 10.04.2010, p. 1835-1842.

Research output: Contribution to journalArticle

Scagliotti, G, Novello, S, Von Pawel, J, Reck, M, Pereira, JR, Thomas, M, Miziara, JEA, Balint, B, De Marinis, F, Keller, A, Arén, O, Csollak, M, Albert, I, Barrios, CH, Grossi, F, Krzakowski, M, Cupit, L, Cihon, F, DiMatteo, S & Hanna, N 2010, 'Phase III study of carboplatin and paclitaxel alone or with sorafenib in advanced non-small-cell lung cancer', Journal of Clinical Oncology, vol. 28, no. 11, pp. 1835-1842. https://doi.org/10.1200/JCO.2009.26.1321
Scagliotti, Giorgio ; Novello, Silvia ; Von Pawel, Joachim ; Reck, Martin ; Pereira, José Rodrigues ; Thomas, Michael ; Miziara, José Elias Abrão ; Balint, Beatrix ; De Marinis, Filippo ; Keller, Alan ; Arén, Osvaldo ; Csollak, Maria ; Albert, Istvan ; Barrios, Carlos Henrique ; Grossi, Francesco ; Krzakowski, Maciej ; Cupit, Lisa ; Cihon, Frank ; DiMatteo, Sandra ; Hanna, Nasser. / Phase III study of carboplatin and paclitaxel alone or with sorafenib in advanced non-small-cell lung cancer. In: Journal of Clinical Oncology. 2010 ; Vol. 28, No. 11. pp. 1835-1842.
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T1 - Phase III study of carboplatin and paclitaxel alone or with sorafenib in advanced non-small-cell lung cancer

AU - Scagliotti, Giorgio

AU - Novello, Silvia

AU - Von Pawel, Joachim

AU - Reck, Martin

AU - Pereira, José Rodrigues

AU - Thomas, Michael

AU - Miziara, José Elias Abrão

AU - Balint, Beatrix

AU - De Marinis, Filippo

AU - Keller, Alan

AU - Arén, Osvaldo

AU - Csollak, Maria

AU - Albert, Istvan

AU - Barrios, Carlos Henrique

AU - Grossi, Francesco

AU - Krzakowski, Maciej

AU - Cupit, Lisa

AU - Cihon, Frank

AU - DiMatteo, Sandra

AU - Hanna, Nasser

PY - 2010/4/10

Y1 - 2010/4/10

N2 - Purpose: This phase III, multicenter, randomized, placebo-controlled trial assessed the efficacy and safety of sorafenib, an oral multikinase inhibitor, in combination with carboplatin and paclitaxel in chemotherapy-naïve patients with unresectable stage IIIB or IV non-small-cell lung cancer (NSCLC). Patients and Methods: Nine hundred twenty-six patients were randomly assigned to receive up to six 21-day cycles of carboplatin area under the curve 6 and paclitaxel 200 mg/m2 (CP) on day 1, followed by either sorafenib 400 mg twice a day (n = 464, arm A) or placebo (n = 462, arm B) on days 2 to 19. The maintenance phase after CP consisted of sorafenib 400 mg or placebo twice a day. The primary end point was overall survival (OS); secondary end points included progression-free survival and tumor response. Results: Overall demographics were balanced between arms; 223 patients (24%) had squamous cell histology. On the basis of a planned interim analysis, median OS was 10.7 months in arm A and 10.6 months in arm B (hazard ratio [HR] = 1.15; 95% CI, 0.94 to 1.41; P = .915). The study was terminated after the interim analysis concluded that the study was highly unlikely to meet its primary end point. A prespecified exploratory analysis revealed that patients with squamous cell histology had greater mortality in arm A than in arm B (HR = 1.85; 95% CI, 1.22 to 2.81). Main grade 3 or 4 sorafenib-related toxicities included rash (8.4%), hand-foot skin reaction (7.8%), and diarrhea (3.5%). Conclusion: No clinical benefit was observed from adding sorafenib to CP chemotherapy as first-line treatment for NSCLC.

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