Pemetrexed, bevacizumab, or the combination as maintenance therapy for advanced nonsquamous non–small-cell lung cancer: ECOG-ACRIN 5508

Suresh S. Ramalingam, Suzanne E. Dahlberg, Chandra P. Belani, Joel N. Saltzman, Nathan A. Pennell, Gopakumar S. Nambudiri, John C. McCann, Jerome D. Winegarden, Mohammed A. Kassem, Mohamed K. Mohamed, Jan M. Rothman, Alan P. Lyss, Leora Horn, Thomas E. Stinchcombe, Joan H. Schiller

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Abstract

PURPOSE Pemetrexed or bevacizumab is used for maintenance therapy of advanced nonsquamous non–small-cell lung cancer (NSCLC). The combination of bevacizumab and pemetrexed has also demonstrated efficacy. We conducted a randomized study to determine the optimal maintenance therapy. PATIENTS AND METHODS Patients with advanced nonsquamous NSCLC and no prior systemic therapy received carboplatin (area under the curve, 6), paclitaxel (200 mg/m2), and bevacizumab (15 mg/kg) for up to four cycles. Patients without progression after four cycles were randomly assigned to maintenance therapy with bevacizumab (15 mg/kg), pemetrexed (500 mg/m2), or a combination of the two agents. The primary end point was overall survival, with bevacizumab serving as the control group. RESULTS Of the 1,516 patients enrolled, 874 (57%) were randomly assigned after induction therapy to one of the three maintenance therapy groups. With a median follow-up of 50.6 months, median survival with pemetrexed was 15.9 months, compared with 14.4 months with bevacizumab (hazard ratio [HR], 0.86; P = .12); median survival with pemetrexed and bevacizumab was 16.4 months (HR, 0.9; P = .28); median progression-free survival was 4.2, 5.1 (HR, 0.85; P = .06), and 7.5 months (HR, 0.67; P, .001) for the three groups, respectively. Incidence of worst grade 3 to 4 toxicity was 29%, 37%, and 51%, respectively, for bevacizumab, pemetrexed, and the combination regimen. CONCLUSION Single-agent bevacizumab or pemetrexed is efficacious as maintenance therapy for advanced nonsquamous NSCLC. Because of a lack of survival benefit and higher toxicity, the combination of bevacizumab and pemetrexed cannot be recommended.

Original languageEnglish (US)
Pages (from-to)2360-2367
Number of pages8
JournalJournal of Clinical Oncology
Volume37
Issue number26
DOIs
StatePublished - Sep 10 2019

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Pemetrexed
Non-Small Cell Lung Carcinoma
Therapeutics
Survival
Bevacizumab
Carboplatin
Group Psychotherapy
Paclitaxel
Disease-Free Survival
Area Under Curve

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Ramalingam, Suresh S. ; Dahlberg, Suzanne E. ; Belani, Chandra P. ; Saltzman, Joel N. ; Pennell, Nathan A. ; Nambudiri, Gopakumar S. ; McCann, John C. ; Winegarden, Jerome D. ; Kassem, Mohammed A. ; Mohamed, Mohamed K. ; Rothman, Jan M. ; Lyss, Alan P. ; Horn, Leora ; Stinchcombe, Thomas E. ; Schiller, Joan H. / Pemetrexed, bevacizumab, or the combination as maintenance therapy for advanced nonsquamous non–small-cell lung cancer : ECOG-ACRIN 5508. In: Journal of Clinical Oncology. 2019 ; Vol. 37, No. 26. pp. 2360-2367.
@article{67de693d074944dfbf4a1a476d5934fa,
title = "Pemetrexed, bevacizumab, or the combination as maintenance therapy for advanced nonsquamous non–small-cell lung cancer: ECOG-ACRIN 5508",
abstract = "PURPOSE Pemetrexed or bevacizumab is used for maintenance therapy of advanced nonsquamous non–small-cell lung cancer (NSCLC). The combination of bevacizumab and pemetrexed has also demonstrated efficacy. We conducted a randomized study to determine the optimal maintenance therapy. PATIENTS AND METHODS Patients with advanced nonsquamous NSCLC and no prior systemic therapy received carboplatin (area under the curve, 6), paclitaxel (200 mg/m2), and bevacizumab (15 mg/kg) for up to four cycles. Patients without progression after four cycles were randomly assigned to maintenance therapy with bevacizumab (15 mg/kg), pemetrexed (500 mg/m2), or a combination of the two agents. The primary end point was overall survival, with bevacizumab serving as the control group. RESULTS Of the 1,516 patients enrolled, 874 (57{\%}) were randomly assigned after induction therapy to one of the three maintenance therapy groups. With a median follow-up of 50.6 months, median survival with pemetrexed was 15.9 months, compared with 14.4 months with bevacizumab (hazard ratio [HR], 0.86; P = .12); median survival with pemetrexed and bevacizumab was 16.4 months (HR, 0.9; P = .28); median progression-free survival was 4.2, 5.1 (HR, 0.85; P = .06), and 7.5 months (HR, 0.67; P, .001) for the three groups, respectively. Incidence of worst grade 3 to 4 toxicity was 29{\%}, 37{\%}, and 51{\%}, respectively, for bevacizumab, pemetrexed, and the combination regimen. CONCLUSION Single-agent bevacizumab or pemetrexed is efficacious as maintenance therapy for advanced nonsquamous NSCLC. Because of a lack of survival benefit and higher toxicity, the combination of bevacizumab and pemetrexed cannot be recommended.",
author = "Ramalingam, {Suresh S.} and Dahlberg, {Suzanne E.} and Belani, {Chandra P.} and Saltzman, {Joel N.} and Pennell, {Nathan A.} and Nambudiri, {Gopakumar S.} and McCann, {John C.} and Winegarden, {Jerome D.} and Kassem, {Mohammed A.} and Mohamed, {Mohamed K.} and Rothman, {Jan M.} and Lyss, {Alan P.} and Leora Horn and Stinchcombe, {Thomas E.} and Schiller, {Joan H.}",
year = "2019",
month = "9",
day = "10",
doi = "10.1200/JCO.19.01006",
language = "English (US)",
volume = "37",
pages = "2360--2367",
journal = "Journal of Clinical Oncology",
issn = "0732-183X",
publisher = "American Society of Clinical Oncology",
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}

Ramalingam, SS, Dahlberg, SE, Belani, CP, Saltzman, JN, Pennell, NA, Nambudiri, GS, McCann, JC, Winegarden, JD, Kassem, MA, Mohamed, MK, Rothman, JM, Lyss, AP, Horn, L, Stinchcombe, TE & Schiller, JH 2019, 'Pemetrexed, bevacizumab, or the combination as maintenance therapy for advanced nonsquamous non–small-cell lung cancer: ECOG-ACRIN 5508', Journal of Clinical Oncology, vol. 37, no. 26, pp. 2360-2367. https://doi.org/10.1200/JCO.19.01006

Pemetrexed, bevacizumab, or the combination as maintenance therapy for advanced nonsquamous non–small-cell lung cancer : ECOG-ACRIN 5508. / Ramalingam, Suresh S.; Dahlberg, Suzanne E.; Belani, Chandra P.; Saltzman, Joel N.; Pennell, Nathan A.; Nambudiri, Gopakumar S.; McCann, John C.; Winegarden, Jerome D.; Kassem, Mohammed A.; Mohamed, Mohamed K.; Rothman, Jan M.; Lyss, Alan P.; Horn, Leora; Stinchcombe, Thomas E.; Schiller, Joan H.

In: Journal of Clinical Oncology, Vol. 37, No. 26, 10.09.2019, p. 2360-2367.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Pemetrexed, bevacizumab, or the combination as maintenance therapy for advanced nonsquamous non–small-cell lung cancer

T2 - ECOG-ACRIN 5508

AU - Ramalingam, Suresh S.

AU - Dahlberg, Suzanne E.

AU - Belani, Chandra P.

AU - Saltzman, Joel N.

AU - Pennell, Nathan A.

AU - Nambudiri, Gopakumar S.

AU - McCann, John C.

AU - Winegarden, Jerome D.

AU - Kassem, Mohammed A.

AU - Mohamed, Mohamed K.

AU - Rothman, Jan M.

AU - Lyss, Alan P.

AU - Horn, Leora

AU - Stinchcombe, Thomas E.

AU - Schiller, Joan H.

PY - 2019/9/10

Y1 - 2019/9/10

N2 - PURPOSE Pemetrexed or bevacizumab is used for maintenance therapy of advanced nonsquamous non–small-cell lung cancer (NSCLC). The combination of bevacizumab and pemetrexed has also demonstrated efficacy. We conducted a randomized study to determine the optimal maintenance therapy. PATIENTS AND METHODS Patients with advanced nonsquamous NSCLC and no prior systemic therapy received carboplatin (area under the curve, 6), paclitaxel (200 mg/m2), and bevacizumab (15 mg/kg) for up to four cycles. Patients without progression after four cycles were randomly assigned to maintenance therapy with bevacizumab (15 mg/kg), pemetrexed (500 mg/m2), or a combination of the two agents. The primary end point was overall survival, with bevacizumab serving as the control group. RESULTS Of the 1,516 patients enrolled, 874 (57%) were randomly assigned after induction therapy to one of the three maintenance therapy groups. With a median follow-up of 50.6 months, median survival with pemetrexed was 15.9 months, compared with 14.4 months with bevacizumab (hazard ratio [HR], 0.86; P = .12); median survival with pemetrexed and bevacizumab was 16.4 months (HR, 0.9; P = .28); median progression-free survival was 4.2, 5.1 (HR, 0.85; P = .06), and 7.5 months (HR, 0.67; P, .001) for the three groups, respectively. Incidence of worst grade 3 to 4 toxicity was 29%, 37%, and 51%, respectively, for bevacizumab, pemetrexed, and the combination regimen. CONCLUSION Single-agent bevacizumab or pemetrexed is efficacious as maintenance therapy for advanced nonsquamous NSCLC. Because of a lack of survival benefit and higher toxicity, the combination of bevacizumab and pemetrexed cannot be recommended.

AB - PURPOSE Pemetrexed or bevacizumab is used for maintenance therapy of advanced nonsquamous non–small-cell lung cancer (NSCLC). The combination of bevacizumab and pemetrexed has also demonstrated efficacy. We conducted a randomized study to determine the optimal maintenance therapy. PATIENTS AND METHODS Patients with advanced nonsquamous NSCLC and no prior systemic therapy received carboplatin (area under the curve, 6), paclitaxel (200 mg/m2), and bevacizumab (15 mg/kg) for up to four cycles. Patients without progression after four cycles were randomly assigned to maintenance therapy with bevacizumab (15 mg/kg), pemetrexed (500 mg/m2), or a combination of the two agents. The primary end point was overall survival, with bevacizumab serving as the control group. RESULTS Of the 1,516 patients enrolled, 874 (57%) were randomly assigned after induction therapy to one of the three maintenance therapy groups. With a median follow-up of 50.6 months, median survival with pemetrexed was 15.9 months, compared with 14.4 months with bevacizumab (hazard ratio [HR], 0.86; P = .12); median survival with pemetrexed and bevacizumab was 16.4 months (HR, 0.9; P = .28); median progression-free survival was 4.2, 5.1 (HR, 0.85; P = .06), and 7.5 months (HR, 0.67; P, .001) for the three groups, respectively. Incidence of worst grade 3 to 4 toxicity was 29%, 37%, and 51%, respectively, for bevacizumab, pemetrexed, and the combination regimen. CONCLUSION Single-agent bevacizumab or pemetrexed is efficacious as maintenance therapy for advanced nonsquamous NSCLC. Because of a lack of survival benefit and higher toxicity, the combination of bevacizumab and pemetrexed cannot be recommended.

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