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.
