Science and Research

Exploratory analysis of front-line therapies in REVEL: a randomised phase 3 study of ramucirumab plus docetaxel versus docetaxel for the treatment of stage IV non-small-cell lung cancer after disease progression on platinum-based therapy

INTRODUCTION: Non-small-cell lung cancer (NSCLC) is a heterogeneous disease. Front-line therapy may affect responses to subsequent treatment regimens, thus influencing second-line therapy decision making. In the randomised phase 3 REVEL study, second-line ramucirumab plus docetaxel (ram+doc) versus docetaxel (doc) improved survival of patients with metastatic NSCLC. We explore efficacy, safety and quality-of-life (QoL) in REVEL based on front-line therapy. METHODS: Patients were grouped by specific front-line therapy received. Overall survival (OS), progression-free survival (PFS), objective response rate, safety and QoL were assessed descriptively. Kaplan-Meier estimation and Cox proportional hazards modelling were used; frequencies reported in percentages. RESULTS: Baseline characteristics of 1253 patients were generally well balanced between treatment arms within each front-line therapy subgroup. For patients with non-squamous disease (n=912), induction therapies included platinum-based chemotherapy plus a taxane (n=227; 25%) or pemetrexed (n=449; 49%), with (n=172; 19%) or without bevacizumab. For patients with squamous disease (n=328), induction therapies included platinum-based chemotherapy plus gemcitabine (n=176; 54%) or a taxane (n=69; 21%). A highly selected subgroup (n=127; 14%) received pemetrexed continuation maintenance therapy. Ram+doc improved median OS and PFS versus doc across front-line therapy subgroups, as reflected by HRs ranging from 0.78 to 0.91 and 0.66 to 0.92, respectively, similar to results in the overall intention-to-treat cohort (HRs: 0.86 and 0.76, respectively). High-grade treatment-emergent adverse events of special interest (including neutropenia, febrile neutropenia, leucopenia and hypertension) were generally higher in ram+doc-treated patients relative to doc-treated patients regardless of front-line therapy. No clear differences in safety or QoL were seen across front-line therapy subgroups; outcomes were consistent with those reported in the overall intention-to-treat cohort. CONCLUSIONS: Results of this exploratory analysis suggest that second-line ram+doc may be effective regardless of prior treatment with platinum-based chemotherapy plus a taxane, pemetrexed, gemcitabine or bevacizumab. Overall, ram+doc is clinically beneficial across a wide range of patients with metastatic NSCLC who have progressed after various front-line therapies. TRIAL REGISTRATION NUMBER: NCT01168973.

  • Garon, E. B.
  • Scagliotti, G. V.
  • Gautschi, O.
  • Reck, M.
  • Thomas, M.
  • Iglesias Docampo, L.
  • Kalofonos, H.
  • Kim, J. H.
  • Gans, S.
  • Brustugun, O. T.
  • Orlov, S. V.
  • Cuyun Carter, G.
  • Zimmermann, A. H.
  • Oton, A. B.
  • Alexandris, E.
  • Lee, P.
  • Wolff, K.
  • Stefaniak, V. J.
  • Socinski, M. A.
  • Perol, M.

Keywords

  • chemotherapy
  • metastatic
  • non-squamous
  • squamous
  • vascular endothelial growth factor receptor
  • AHZ, ABO, PL, KW, and VJS are full-time employees and stockowners of Eli Lilly
  • and Company. EA is a former employee and stockowner of Eli Lilly and Company. EBG
  • has received honoraria from Dracen and EMD Serono, and his institution has
  • received research funding from AstraZeneca, Bristol Myers Squibb, Merck, Eli
  • Lilly and Company, Novartis, Genentech, Dynavax, Iovance, Mirati, and Neon. GVS
  • has received honoraria from Eli Lilly and Company, AstraZeneca, Clovis Oncology,
  • Regeneron, Novartis, Merck Sharp and Dohme, Pfizer, and Roche and has served on
  • the speaker's bureaus of Eli Lilly and Company, AstraZeneca, Merck Sharp and
  • Dohme, and Novartis. MR has received honoraria for lectures from and functions in
  • an advisory/consulting role for Eli Lilly and Company, AstraZeneca, Boehringer
  • Ingelheim, Bristol Myers Squibb, Celgene, Hoffman-La Roche, Merck, Novartis, and
  • Pfizer. MT has received Advisory Board honoraria from AbbVie, Bristol Myers
  • Squibb, Boehringer, Celgene, Eli Lilly and Company, Merck Sharp and Dohme,
  • Novartis, Roche, Takeda
  • speaker's honoraria from Eli Lilly and Company, Merck
  • Sharp and Dohme, Takeda
  • research funding from AstraZeneca, Bristol Myers Squibb,
  • Celgene, Roche
  • and travel grants from Bristol Myers Squibb, Boehringer, Merck
  • Sharp and Dohme, and Novartis. HK has received reimbursement for meeting expenses
  • and/or has functioned in an advisory/consultancy role for Eli Lilly and Company,
  • Genesis Pharma, GlaxoSmithKline, Merck, Novartis, Pfizer, and Roche and has
  • received reimbursement for meeting expenses from Enorasis. J-HK serves in an
  • advisory/consultancy role for and his institution has received grant funding for
  • clinical trials from Eli Lilly and Company, including during the conduct of this
  • study, and from AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, and
  • Roche. OTB has received honoraria from Eli Lilly and Company, AstraZeneca,
  • Boehringer Ingelheim (for research funding and advisory/consultancy role),
  • GlaxoSmithKline (for research funding), Merck (for advisory/consultancy role),
  • Novartis, Pfizer, and Roche (for research funding). MP has received honoraria for
  • speaking, advisory and consultancy roles for Eli Lilly and Company.
Publication details
DOI: 10.1136/esmoopen-2019-000567
Journal: ESMO Open
Number: 1
Work Type: Original
Location: ARCN, TLRC
Disease Area: LC
Partner / Member: Ghd, UKHD
Access-Number: 31958290
See publication on PubMed

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