Sunitinib plus erlotinib versus placebo plus erlotinib in patients with previously treated advanced non-small-cell lung cancer: A phase III trial

Giorgio V. Scagliotti, Maciej Krzakowski, Aleksandra Szczesna, J. Strausz, Anatoly Makhson, Martin Reck, Rafal F. Wierzbicki, Istvan Albert, Michael Thomas, Jose Elias Abrao Miziara, Zsolt S. Papai, Nina Karaseva, Sumitra Thongprasert, Elsa Dalmau Portulas, Joachim Von Pawel, Ke Zhang, Paulina Selaru, Lesley Tye, Richard C. Chao, Ramaswamy Govindan

Research output: Article

159 Citations (Scopus)

Abstract

Purpose: Sunitinib plus erlotinib may enhance antitumor activity compared with either agent alone in non-small-cell lung cancer (NSCLC), based on the importance of the signaling pathways involved in tumor growth, angiogenesis, and metastasis. This phase III trial investigated overall survival (OS) for sunitinib plus erlotinib versus placebo plus erlotinib in patients with refractory NSCLC. Patients and Methods: Patients previously treated with one to two chemotherapy regimens (including one platinumbased regimen) for recurrent NSCLC, and for whom erlotinib was indicated, were randomly assigned (1:1) to sunitinib 37.5 mg/d plus erlotinib 150 mg/d or to placebo plus erlotinib 150 mg/d, stratified by prior bevacizumab use, smoking history, and epidermal growth factor receptor expression. The primary end point was OS. Key secondary end points included progression-free survival (PFS), objective response rate (ORR), and safety. Results: In all, 960 patients were randomly assigned, and baseline characteristics were balanced. Median OS was 9.0 months for sunitinib plus erlotinib versus 8.5 months for erlotinib alone (hazard ratio [HR], 0.922; 95% CI, 0.797 to 1.067; one-sided stratified log-rank P = .1388). Median PFS was 3.6 months versus 2.0 months (HR, 0.807; 95% CI, 0.695 to 0.937; one-sided stratified log-rank P =.0023), and ORR was 10.6% versus 6.9% (two-sided stratified log-rank P = .0471), respectively. Treatment-related toxicities of grade 3 or higher, including rash/dermatitis, diarrhea, and asthenia/fatigue were more frequent in the sunitinib plus erlotinib arm. Conclusion: In patients with refractory NSCLC, sunitinib plus erlotinib did not improve OS compared with erlotinib alone, but the combination was associated with a statistically significantly longer PFS and greater ORR. The incidence of grade 3 or higher toxicities was greater with combination therapy.

Original languageEnglish
Pages (from-to)2070-2078
Number of pages9
JournalJournal of Clinical Oncology
Volume30
Issue number17
DOIs
Publication statusPublished - jún. 10 2012

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Non-Small Cell Lung Carcinoma
Placebos
Disease-Free Survival
Survival
Erlotinib Hydrochloride
sunitinib
Asthenia
Dermatitis
Exanthema
Epidermal Growth Factor Receptor
Fatigue
Diarrhea
Smoking
History
Neoplasm Metastasis
Safety
Drug Therapy
Incidence

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Sunitinib plus erlotinib versus placebo plus erlotinib in patients with previously treated advanced non-small-cell lung cancer : A phase III trial. / Scagliotti, Giorgio V.; Krzakowski, Maciej; Szczesna, Aleksandra; Strausz, J.; Makhson, Anatoly; Reck, Martin; Wierzbicki, Rafal F.; Albert, Istvan; Thomas, Michael; Miziara, Jose Elias Abrao; Papai, Zsolt S.; Karaseva, Nina; Thongprasert, Sumitra; Portulas, Elsa Dalmau; Von Pawel, Joachim; Zhang, Ke; Selaru, Paulina; Tye, Lesley; Chao, Richard C.; Govindan, Ramaswamy.

In: Journal of Clinical Oncology, Vol. 30, No. 17, 10.06.2012, p. 2070-2078.

Research output: Article

Scagliotti, GV, Krzakowski, M, Szczesna, A, Strausz, J, Makhson, A, Reck, M, Wierzbicki, RF, Albert, I, Thomas, M, Miziara, JEA, Papai, ZS, Karaseva, N, Thongprasert, S, Portulas, ED, Von Pawel, J, Zhang, K, Selaru, P, Tye, L, Chao, RC & Govindan, R 2012, 'Sunitinib plus erlotinib versus placebo plus erlotinib in patients with previously treated advanced non-small-cell lung cancer: A phase III trial', Journal of Clinical Oncology, vol. 30, no. 17, pp. 2070-2078. https://doi.org/10.1200/JCO.2011.39.2993
Scagliotti, Giorgio V. ; Krzakowski, Maciej ; Szczesna, Aleksandra ; Strausz, J. ; Makhson, Anatoly ; Reck, Martin ; Wierzbicki, Rafal F. ; Albert, Istvan ; Thomas, Michael ; Miziara, Jose Elias Abrao ; Papai, Zsolt S. ; Karaseva, Nina ; Thongprasert, Sumitra ; Portulas, Elsa Dalmau ; Von Pawel, Joachim ; Zhang, Ke ; Selaru, Paulina ; Tye, Lesley ; Chao, Richard C. ; Govindan, Ramaswamy. / Sunitinib plus erlotinib versus placebo plus erlotinib in patients with previously treated advanced non-small-cell lung cancer : A phase III trial. In: Journal of Clinical Oncology. 2012 ; Vol. 30, No. 17. pp. 2070-2078.
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abstract = "Purpose: Sunitinib plus erlotinib may enhance antitumor activity compared with either agent alone in non-small-cell lung cancer (NSCLC), based on the importance of the signaling pathways involved in tumor growth, angiogenesis, and metastasis. This phase III trial investigated overall survival (OS) for sunitinib plus erlotinib versus placebo plus erlotinib in patients with refractory NSCLC. Patients and Methods: Patients previously treated with one to two chemotherapy regimens (including one platinumbased regimen) for recurrent NSCLC, and for whom erlotinib was indicated, were randomly assigned (1:1) to sunitinib 37.5 mg/d plus erlotinib 150 mg/d or to placebo plus erlotinib 150 mg/d, stratified by prior bevacizumab use, smoking history, and epidermal growth factor receptor expression. The primary end point was OS. Key secondary end points included progression-free survival (PFS), objective response rate (ORR), and safety. Results: In all, 960 patients were randomly assigned, and baseline characteristics were balanced. Median OS was 9.0 months for sunitinib plus erlotinib versus 8.5 months for erlotinib alone (hazard ratio [HR], 0.922; 95{\%} CI, 0.797 to 1.067; one-sided stratified log-rank P = .1388). Median PFS was 3.6 months versus 2.0 months (HR, 0.807; 95{\%} CI, 0.695 to 0.937; one-sided stratified log-rank P =.0023), and ORR was 10.6{\%} versus 6.9{\%} (two-sided stratified log-rank P = .0471), respectively. Treatment-related toxicities of grade 3 or higher, including rash/dermatitis, diarrhea, and asthenia/fatigue were more frequent in the sunitinib plus erlotinib arm. Conclusion: In patients with refractory NSCLC, sunitinib plus erlotinib did not improve OS compared with erlotinib alone, but the combination was associated with a statistically significantly longer PFS and greater ORR. The incidence of grade 3 or higher toxicities was greater with combination therapy.",
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T1 - Sunitinib plus erlotinib versus placebo plus erlotinib in patients with previously treated advanced non-small-cell lung cancer

T2 - A phase III trial

AU - Scagliotti, Giorgio V.

AU - Krzakowski, Maciej

AU - Szczesna, Aleksandra

AU - Strausz, J.

AU - Makhson, Anatoly

AU - Reck, Martin

AU - Wierzbicki, Rafal F.

AU - Albert, Istvan

AU - Thomas, Michael

AU - Miziara, Jose Elias Abrao

AU - Papai, Zsolt S.

AU - Karaseva, Nina

AU - Thongprasert, Sumitra

AU - Portulas, Elsa Dalmau

AU - Von Pawel, Joachim

AU - Zhang, Ke

AU - Selaru, Paulina

AU - Tye, Lesley

AU - Chao, Richard C.

AU - Govindan, Ramaswamy

PY - 2012/6/10

Y1 - 2012/6/10

N2 - Purpose: Sunitinib plus erlotinib may enhance antitumor activity compared with either agent alone in non-small-cell lung cancer (NSCLC), based on the importance of the signaling pathways involved in tumor growth, angiogenesis, and metastasis. This phase III trial investigated overall survival (OS) for sunitinib plus erlotinib versus placebo plus erlotinib in patients with refractory NSCLC. Patients and Methods: Patients previously treated with one to two chemotherapy regimens (including one platinumbased regimen) for recurrent NSCLC, and for whom erlotinib was indicated, were randomly assigned (1:1) to sunitinib 37.5 mg/d plus erlotinib 150 mg/d or to placebo plus erlotinib 150 mg/d, stratified by prior bevacizumab use, smoking history, and epidermal growth factor receptor expression. The primary end point was OS. Key secondary end points included progression-free survival (PFS), objective response rate (ORR), and safety. Results: In all, 960 patients were randomly assigned, and baseline characteristics were balanced. Median OS was 9.0 months for sunitinib plus erlotinib versus 8.5 months for erlotinib alone (hazard ratio [HR], 0.922; 95% CI, 0.797 to 1.067; one-sided stratified log-rank P = .1388). Median PFS was 3.6 months versus 2.0 months (HR, 0.807; 95% CI, 0.695 to 0.937; one-sided stratified log-rank P =.0023), and ORR was 10.6% versus 6.9% (two-sided stratified log-rank P = .0471), respectively. Treatment-related toxicities of grade 3 or higher, including rash/dermatitis, diarrhea, and asthenia/fatigue were more frequent in the sunitinib plus erlotinib arm. Conclusion: In patients with refractory NSCLC, sunitinib plus erlotinib did not improve OS compared with erlotinib alone, but the combination was associated with a statistically significantly longer PFS and greater ORR. The incidence of grade 3 or higher toxicities was greater with combination therapy.

AB - Purpose: Sunitinib plus erlotinib may enhance antitumor activity compared with either agent alone in non-small-cell lung cancer (NSCLC), based on the importance of the signaling pathways involved in tumor growth, angiogenesis, and metastasis. This phase III trial investigated overall survival (OS) for sunitinib plus erlotinib versus placebo plus erlotinib in patients with refractory NSCLC. Patients and Methods: Patients previously treated with one to two chemotherapy regimens (including one platinumbased regimen) for recurrent NSCLC, and for whom erlotinib was indicated, were randomly assigned (1:1) to sunitinib 37.5 mg/d plus erlotinib 150 mg/d or to placebo plus erlotinib 150 mg/d, stratified by prior bevacizumab use, smoking history, and epidermal growth factor receptor expression. The primary end point was OS. Key secondary end points included progression-free survival (PFS), objective response rate (ORR), and safety. Results: In all, 960 patients were randomly assigned, and baseline characteristics were balanced. Median OS was 9.0 months for sunitinib plus erlotinib versus 8.5 months for erlotinib alone (hazard ratio [HR], 0.922; 95% CI, 0.797 to 1.067; one-sided stratified log-rank P = .1388). Median PFS was 3.6 months versus 2.0 months (HR, 0.807; 95% CI, 0.695 to 0.937; one-sided stratified log-rank P =.0023), and ORR was 10.6% versus 6.9% (two-sided stratified log-rank P = .0471), respectively. Treatment-related toxicities of grade 3 or higher, including rash/dermatitis, diarrhea, and asthenia/fatigue were more frequent in the sunitinib plus erlotinib arm. Conclusion: In patients with refractory NSCLC, sunitinib plus erlotinib did not improve OS compared with erlotinib alone, but the combination was associated with a statistically significantly longer PFS and greater ORR. The incidence of grade 3 or higher toxicities was greater with combination therapy.

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