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.

Abstract

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.

• Authors: Edward B Garon, Giorgio Vittorio Scagliotti, Oliver Gautschi, Martin Reck, Michael Thomas, Lara Iglesias Docampo, Haralabos Kalofonos, Joo-Hang Kim, Steven Gans, Odd Terje Brustugun, Sergey V Orlov, Gebra Cuyun Carter, Annamaria H Zimmermann, Ana B Oton, Ekaterine Alexandris, Pablo Lee, Katharina Wolff, Victoria Jennifer Stefaniak, Mark A Socinski, Maurice Pérol
• Journal: ESMO open (ESMO Open) Vol. 5 Issue 1 (01 2020) ISSN: 2059-7029 [Electronic] England
• PMID: 31958290 (Publication Type: Clinical Trial, Phase III, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: © Author (s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. Published by BMJ on behalf of the European Society for Medical Oncology.

Chemical References

• Antibodies, Monoclonal, Humanized
• Docetaxel
• Platinum
• ramucirumab

Topics

• Antibodies, Monoclonal, Humanized (pharmacology, therapeutic use)
• Antineoplastic Combined Chemotherapy Protocols (pharmacology, therapeutic use)
• Carcinoma, Non-Small-Cell Lung (drug therapy)
• Disease Progression
• Docetaxel (pharmacology, therapeutic use)
• Female
• Humans
• Lung Neoplasms (drug therapy)
• Neoplasm Staging
• Platinum (therapeutic use)