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Table of Contents
ORIGINAL ARTICLE
Year : 2021  |  Volume : 4  |  Issue : 4  |  Page : 634-641

A multicenter, double-blind, randomized phase III trial of ramucirumab plus docetaxel versus placebo plus docetaxel for treatment of Stage IV non-small cell lung cancer after disease progression on or after platinum-based therapy (REVEL): An Indian patient subgroup analysis


1 Department of Medical Oncology, Tata Memorial Hospital, Mumbai, Maharashtra, India
2 Department of Medical Oncology, Rajiv Gandhi Cancer Institute, Coimbatore, Tamil Nadu, India
3 Department of Medical Oncology, KMCH Institute of Health Sciences and Research, Coimbatore, Tamil Nadu, India
4 Department of Medical Oncology, Bhagwan Mahaveer Cancer Hospital & Research Centre, Jaipur, India
5 Eli Lilly and Company, Gurgaon, Haryana, India
6 Eli Lilly and Company, Indianapolis, Indiana, USA

Date of Submission09-Jul-2021
Date of Decision17-Aug-2021
Date of Acceptance24-Nov-2021
Date of Web Publication29-Dec-2021

Correspondence Address:
Kumar Prabhash
Department of Medical Oncology, Tata Memorial Hospital, Mumbai, Maharashtra
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/crst.crst_159_21

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  Abstract 


Background: Ramucirumab plus docetaxel has been shown to improve survival as a second-line treatment for patients with Stage IV non-small-cell lung cancer (NSCLC) in the multicenter, double-blind, randomized, Phase III trial, REVEL.
Objective: In this exploratory analysis, we aimed to assess the safety and efficacy of ramucirumab plus docetaxel in the Indian patient subgroup of the REVEL study.
Materials and Methods: Adult patients with histologically or cytologically confirmed NSCLC of either squamous or non-squamous histology, who progressed during or after first-line platinum-based chemotherapy were randomized to receive either ramucirumab plus docetaxel or placebo plus docetaxel. We performed a descriptive analysis of the baseline characteristics, safety, and efficacy of the Indian subgroup of the overall REVEL study (NCT01168973). The analyses presented here are not intended for comparison purposes either between treatment arms or to the overall REVEL study.
Results: Fifty-five Indian patients were included in the REVEL study. Baseline characteristics and prior therapies of these patients were well-balanced between the treatment arms. Almost 80% patients had non-squamous histology, and 78.2% were men. All patients had received prior standard platinum-based therapy: 25.5% of patients received maintenance, while 18.2% received taxane (paclitaxel only) as part of their first-line therapy. The incidence of treatment-emergent adverse events regardless of grade was similar between the two arms in the Indian safety subgroup. Patients treated with ramucirumab plus docetaxel experienced a median overall survival (OS) of 13.5 months (95% confidence interval [CI], 5.7–17.6) and progression-free survival (PFS) of 5.6 months (95% CI, 2.8–7.0) relative to a median OS of 5.3 months (95% CI: 3.6–9.9) and PFS of 1.5 months (95% CI: 1.3–5.2), for those treated with placebo plus docetaxel.
Conclusion: In this exploratory analysis, Indian patients enrolled in the REVEL study demonstrated prolonged OS and PFS when treated with ramucirumab plus docetaxel, consistent with the overall results of the REVEL study. Ramucirumab plus docetaxel appears to be well tolerated by Indian patients, as the rates for most adverse events were similar with and without ramucirumab.

Keywords: Carcinoma, non-small cell lung, docetaxel; progression-free survival, ramucirumab, overall survival


How to cite this article:
Prabhash K, Doval D C, Rangarajan B, Somani N, Pruthi A, Dyachkova Y, Puri T. A multicenter, double-blind, randomized phase III trial of ramucirumab plus docetaxel versus placebo plus docetaxel for treatment of Stage IV non-small cell lung cancer after disease progression on or after platinum-based therapy (REVEL): An Indian patient subgroup analysis. Cancer Res Stat Treat 2021;4:634-41

How to cite this URL:
Prabhash K, Doval D C, Rangarajan B, Somani N, Pruthi A, Dyachkova Y, Puri T. A multicenter, double-blind, randomized phase III trial of ramucirumab plus docetaxel versus placebo plus docetaxel for treatment of Stage IV non-small cell lung cancer after disease progression on or after platinum-based therapy (REVEL): An Indian patient subgroup analysis. Cancer Res Stat Treat [serial online] 2021 [cited 2022 Jan 21];4:634-41. Available from: https://www.crstonline.com/text.asp?2021/4/4/634/334176




  Introduction Top


Despite advances in our understanding of the risk, biology, immunologic control, and newer treatment options, lung cancer continues to be the leading cause of death from cancer worldwide. According to the GLOBOCAN 2020 report, the estimated overall incidence of lung cancer in India was 72,510, making it the 4th most commonly diagnosed cancer, excluding non-melanoma skin cancer, after breast, oral cavity, and cervical cancers. In 2020, lung cancer resulted in 66,279 deaths, representing 7.8% of deaths from all cancers in India, with a cumulative risk of 0.61.[1]

Non-small cell lung cancer (NSCLC) is the most prevalent type of lung cancer, accounting for 84% of all lung cancers.[2] Globally, approximately 85% of patients with NSCLC present with advanced or metastatic disease at diagnosis; a recent large cohort analysis in India demonstrated that 95% of patients with NSCLC are diagnosed at an advanced stage,[3] with the vast majority presenting with disseminated disease.[4] The objective of treatment in this patient population is palliative and includes the slowing of disease progression, maintaining or preventing the worsening of symptoms and quality of life, and, whenever possible, to increase the overall survival (OS).[5] However, regardless of the initial treatment, most patients with advanced NSCLC experience relapse and disease progression.

For many decades, chemotherapy has been the standard of care for patients with NSCLC. In India, the recently updated guidelines state that all patients with advanced NSCLC, with a performance status (PS) of 0–2, without driver mutations or rearrangements, and programmed death-ligand 1 (PD-L1) expression of <50% should be treated with upfront chemotherapy,[6] while patients with PD-L1 ≥50% may be treated with pembrolizumab or pemetrexed and a platinum agent in the first line. The addition of bevacizumab, a recombinant humanized monoclonal antibody against vascular endothelial growth factor (VEGF), to first-line carboplatin-paclitaxel combination chemotherapy led to a significant improvement in OS in eligible patients with non-squamous NSCLC.[7] It is now a standard first-line treatment option for qualified patients with advanced non-squamous NSCLC without actionable biomarkers.[8]

In the second-line setting, the Indian guidelines indicate that for patients with NSCLC whose disease is PD-L1 negative/unknown, atezolizumab or nivolumab could be considered. For patients with PD-L1 expression >1%, pembrolizumab is an option. For patients with rapid progression (defined as progression in <9 months from the start of their first-line therapy) and those with progressive disease as the best response to first-line therapy, docetaxel in combination with either nintedanib or ramucirumab is an acceptable alternative. For patients who are unable to afford the treatment costs associated with the above agents, single-agent docetaxel or pemetrexed, if not already used in the first line, are preferred. Finally, for patients with an unknown epidermal growth factor receptor (EGFR) status, those with poor PS, and those who are unwilling to use chemotherapy/immunotherapy, EGFR-tyrosine kinase inhibitors (TKIs) may be used as second-line therapy.[6]

Although immune checkpoint inhibitors provide durable responses and extended long-term survival in patients with advanced NSCLC, the overall response rates are only about 16%–20%.[9],[10],[11] Furthermore, the high cost of immunotherapy may create access barriers. Reduced patient PS and low response rates suggest that tolerability and tumor control are paramount in the second line. Furthermore, following progression on first-line treatment, the disease often becomes more symptomatic, meaning that control of symptoms and their alleviation is highly desirable. A review of recently published observational studies demonstrated that, worldwide, the proportion of patients with advanced NSCLC receiving second-line treatment was 53% or less.[12] Although the reasons for the lack of second-line treatment were not addressed in the original studies, poor PS, advanced age, and poor response to first-line treatment may all be contributing factors. Therefore, treatments with different mechanisms of action such as EGFR or angiogenesis inhibition may offer previously treated patients with advanced NSCLC an opportunity to receive second-line therapy.

One of the hallmarks of cancer, angiogenesis, is a major contributor to cancer growth and metastasis.[13] Blockade of VEGF receptor 2 (VEGFR2) signaling has been shown to inhibit the formation, proliferation, and migration of new blood vessels. Ramucirumab (Cyramza®, LY3009806) is a recombinant human immunoglobulin 1 (IgG1) monoclonal antibody receptor antagonist designed to bind to the extracellular domain of VEGFR2, thereby blocking the binding of multiple VEGF ligands and inhibiting receptor activation.[14] Docetaxel, approved by regulatory agencies for second-line treatment for patients with NSCLC, was considered to be an appropriate agent for combination therapy with ramucirumab, given its efficacy independent of the baseline histology or EGFR mutation status in patients with NSCLC.[15] Furthermore, based on preclinical and early clinical data, the addition of ramucirumab to docetaxel-based chemotherapy was not expected to significantly affect the rate of docetaxel-associated adverse events (AEs).[14],[16]

Response to cancer therapies and their AE profiles in the Indian population may differ from those of patients from other regions due to geographic variations in clinical practice and differences in drug metabolism. Therefore, it is important to evaluate the efficacy and safety of cancer therapies within the Indian population. This analysis was performed to enable a better understanding of ramucirumab and docetaxel amongst Indian oncologists by providing data specific to the Indian population, primarily on tolerability which may inform their treatment decisions for patients with stage IV NSCLC.


  Materials and Methods Top


General study details

The REVEL trial was a randomized, double-blind, placebo-controlled Phase III study that compared ramucirumab plus docetaxel with placebo plus docetaxel in adult (aged ≥18 years) patients with Stage IV NSCLC who had progressed during or after first-line, platinum-based chemotherapy for advanced or metastatic disease.[17] Enrollment for the REVEL study took place between December 03, 2010, and January 24, 2013, at academic medical centers and community clinics in 26 countries in 6 continents. The protocol was approved by site-specific ethics review boards. The study conduct was guided by principles of good clinical practice and the Declaration of Helsinki. All patients provided informed consent in writing before treatment initiation. The study is registered with ClinicalTrials.gov, number NCT01168973. The study sponsor, Ely Lilly, provided the study drug and collaborated with investigators on all aspects of the study, including the preparation of this report.

Participants

Eligible patients had pathologically confirmed (squamous or non-squamous) stage IV NSCLC that had progressed during or after a single platinum-based chemotherapy treatment regimen, irrespective of prior bevacizumab or maintenance therapy.

Patients with recurrent disease who had previously received adjuvant or neoadjuvant therapy or chemoradiotherapy for locally advanced disease were included if their disease had progressed in the 6 months after completion of adjuvant or neoadjuvant platinum-based therapy, or if their disease had progressed after 6 months following therapy and during or after one subsequent platinum-based chemotherapy regimen.

Patients were eligible for inclusion in REVEL if their disease was measurable or non-measurable (according to the Response Evaluation Criteria in Solid Tumors [RECIST] version 1.1)[18]) with an Eastern Cooperative Oncology Group (ECOG) PS of 0 or 1.

Key exclusion criteria included poorly controlled hypertension, a recent arterial thromboembolic event (within 6 months prior to randomization), gastrointestinal perforation or fistulae, major blood vessel involvement, intratumor cavitation, gross hemoptysis in the last 2 months, or grade 3–4 gastrointestinal bleeding (as defined by the National Cancer Institute Common Terminology Criteria for Adverse Events [NCI-CTCAE], version 4.0)[19] within the last 3 months. Patients who had only received EGFR TKI monotherapy for advanced or metastatic disease were excluded.

Variables

OS measured from randomization to death from any cause was the primary endpoint of the REVEL study. Progression-free survival (PFS) measured from randomization till progression or death due to any cause, objective response rate (ORR) defined as the percentage of patients with a complete response or partial response as assessed by investigators according to RECIST 1.1 at 6-week intervals, and disease control rate (DCR) defined as the percentage of patients with tumor response or stable disease were the secondary endpoints. AEs were reported according to NCI-CTCAE v4.03.[19]

Study methodology

Patients were randomly assigned in a 1:1 ratio to receive either:

  • Ramucirumab (10 mg/kg, 60-min intravenous [IV] infusion) in combination with docetaxel (75 mg/m2, 60-min IV infusion) administered on day 1 of a 21-day cycle
  • Placebo (10 mg/kg, 60-min IV infusion) in combination with docetaxel (75 mg/m2, 60-min IV infusion) administered on day 1 of a 21-day cycle.


Radiological assessment of the disease status using computed tomography (CT) scan or magnetic resonance imaging (MRI) was carried out according to RECIST, v 1.1[18] every 6 weeks, from the first dose of study therapy until radiographic disease progression was noted. This method of assessment and technique was also used to characterize each identified and reported lesion at baseline and during the study. Patients were treated until radiographic or symptomatic progressive disease was evident, toxicity requiring cessation was noted, patient consent was withdrawn, or until other withdrawal criteria were met. Following the decision to discontinue study treatment, information related to AEs was collected for at least an additional 30 days. After the 30-day post-discontinuation visit, information related only to the new and ongoing serious AEs that were deemed related to the study treatment were collected.

Patient randomization and procedures for REVEL have previously been described.[17] Stratification factors included ECOG PS (0 vs. 1); sex (female vs. male); prior maintenance therapy (yes vs. no), and geographic region (East Asia vs. rest of the world). All drugs were administered through IV infusion once every 3 weeks in the absence of progressive disease or other withdrawal criteria.

Statistics

The primary endpoint of the REVEL study was OS, therefore, it was used for the overall study sample size calculation as described.[17] This report describes a subgroup analysis of Indian patients who participated in the study. Kaplan–Meier method was used to assess OS and PFS, including medians and 95% confidence intervals (CIs). Rates and proportions were used for description of ORR, DCR, and safety events. This is an exploratory analysis, and hence, P values are not reported. Descriptive statistics, including medians, ranges, frequencies, and percentages are used in this report. Safety analyses were performed on all randomized Indian patients who received any dose of study medication. SAS software, Version 9.1.2 (SAS Institute Inc., Cary, NC, USA) or higher was used for all statistical analyses.


  Results Top


In India, patients enrolled on the REVEL study were treated at nine study sites. A total of 55 Indian patients were randomized to treatment, 22 patients in the ramucirumab plus docetaxel arm and 33 patients in the placebo plus docetaxel arm, hereafter known as the REVEL India subgroup.

Baseline demographics and disease characteristics are described in [Table 1]. The median age of the patients in the REVEL India subgroup was 53 (range: 30–71) years, and all patients were <75 years of age; most patients were male (78.2%). All included patients had received prior standard platinum-based therapy: 25.5% had received maintenance therapy and 18.2% received taxane (paclitaxel only) as part of their first-line therapy. Non-squamous histology was the most prevalent (78.2%). Treatment arms in the REVEL India subgroup were balanced with respect to patient demographics and other baseline disease characteristics, with the following exceptions: there was a lower proportion of female patients in the ramucirumab plus docetaxel arm (13.6%) than in the placebo plus docetaxel arm (27.3%), and there was a higher proportion of patients who had squamous cell carcinoma in the ramucirumab plus docetaxel arm (27.3%) than in the placebo plus docetaxel arm (18.2%).
Table 1: Baseline demographics and disease characteristics of the Indian subgroup

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Of the 55 randomized patients, 54 received at least one dose of study therapy, including 22 patients in the ramucirumab plus docetaxel arm and 32 patients in the placebo plus docetaxel arm; these patients comprised the REVEL India Safety subgroup. One patient randomized to receive placebo plus docetaxel did not receive the study treatment. The overall median duration of therapy was 18.1 (range, 3–44) weeks for the ramucirumab plus docetaxel arm compared to 6.1 (range, 3–66) weeks for the placebo plus docetaxel arm.

A greater proportion of patients in the ramucirumab plus docetaxel arm compared to placebo plus docetaxel arm experienced dose delays (63.6% vs. 21.9%, respectively) and dose reductions (22.7% vs. 6.3%, respectively) for any study drug. The proportion of patients with dose omissions was low and similar between the two arms (4.5% and 3.1%, respectively).

A higher proportion of patients in the ramucirumab plus docetaxel arm compared to the placebo plus docetaxel arm experienced dose delays of ramucirumab/placebo (59.1% vs. 18.8%, respectively). The proportion of patients with dose omissions of ramucirumab/placebo was low and similar between the two arms (no patients [0%] in the ramucirumab plus docetaxel arm and 1 patient [3.1%] in the placebo plus docetaxel arm). Dose reductions of ramucirumab/placebo were also low and similar between the two arms (1 patient [4.5%] in the ramucirumab plus docetaxel arm and no patients [0%] in the placebo plus docetaxel arm).

The incidence of treatment-emergent adverse events regardless of the grade was similar between the two arms in the REVEL India Safety subgroup. All 22 patients in the ramucirumab plus docetaxel arm and 30 patients (93.8%) in the placebo plus docetaxel arm experienced at least 1 treatment-emergent adverse event [Table 2]. The incidence of grade ≥3 treatment-emergent adverse events, regardless of causality, was higher in the ramucirumab plus docetaxel arm (81.8%) than in the placebo plus docetaxel arm (71.9%) [Table 2]. Fatigue, cough, neutropenia, back pain, decreased appetite, and pain were the grade ≥3 adverse events that occurred more frequently in the ramucirumab plus docetaxel arm, while the incidence of diarrhea was 13.6% in the ramucirumab plus docetaxel arm relative to 0% in the placebo plus docetaxel arm.
Table 2: Treatment emergent adverse events occurring in at least 20% of patients in the ramucirumab plus docetaxel arm, by the medical dictionary for regulatory activities preferred term - any grade and Grade ≥3 - REVEL India safety subgroup

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Adverse events of special interest are pre-specified selected adverse events of clinical interest that have been associated with antiangiogenic agents. The AEs that are considered to be adverse events of special interest for ramucirumab include arterial thromboembolism, venous thromboembolism, bleeding/hemorrhage events including pulmonary hemorrhage events, hypertension, infusion-related reaction, and liver failure or liver injury. Adverse events of special interest were infrequent (<20% of the subgroup) and are therefore not included in [Table 2].

In the Indian subgroup, the proportion of patients with bleeding events of any grade was somewhat lower in the ramucirumab plus docetaxel arm compared to the placebo plus docetaxel arm (9.1% vs. 18.8%, corresponding to 2 and 6 patients, respectively). The incidence of bleeding/hemorrhagic events of epistaxis was similar between the ramucirumab plus docetaxel arm and the placebo plus docetaxel arm (4.5% and 3.1%, 1 patient in each arm, respectively). The incidence of gingival bleeding was potentially increased in the ramucirumab plus docetaxel arm relative to the placebo plus docetaxel arm (4.5% vs. 0%, respectively, corresponding to just 1 patient with an event). The incidence of hemoptysis was lower in the ramucirumab plus docetaxel arm compared to the placebo plus docetaxel arm (0% vs. 18.8%, 0 vs. 6 patients, respectively). Of these 6 hemoptysis events in the placebo plus docetaxel arm, 2 were of grade 3 or higher (both grade 5). All hemoptysis events were considered pulmonary hemorrhage events.

The proportion of patients with any grade hypertension was similar between the ramucirumab plus docetaxel arm and placebo plus docetaxel arm (4.5% vs. 3.1%, respectively, 1 patient each). There was a single report of grade ≥3 hypertension in the ramucirumab plus docetaxel arm and no reports of grade ≥3 hypertension in the placebo plus docetaxel arm.

Events of liver failure or injury, including liver infection, were identified based on the Standard Medical Dictionary for Regulatory Activities Query for hepatic disorders. No patients in the ramucirumab plus docetaxel arm experienced liver failure or injury. One patient in the placebo plus docetaxel arm experienced a Grade 4 liver-related event (laboratory) of increased gamma-glutamyl transferase.

There was a numeric improvement of 8.2 months in median OS in the ramucirumab plus docetaxel arm over the placebo plus docetaxel (13.5 months [95% confidence interval {CI}, 5.7–17.6] vs. 5.3 months [95% CI, 3.6–9.9], respectively). [Figure 1] shows the Kaplan–Meier curve for OS.
Figure 1: Kaplan–Meier curve for overall survival by treatment arm, REVEL India Subgroup. CI: confidence interval, DOC: Docetaxel, PBO: Placebo, RAM: Ramucirumab

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There was a numerically 4.1 month longer median PFS in the ramucirumab plus docetaxel arm than the placebo plus docetaxel arm (5.6 months [95% CI, 2.8–7.0] vs. 1.5 months [95% CI, 1.3–5.2], respectively) [Figure 2].
Figure 2: Kaplan–Meier curve for progression-free survival by treatment arm, REVEL India Subgroup. CI: Confidence interval, DOC: Docetaxel; PBO: Placebo; RAM: Ramucirumab

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The ORR for the REVEL India subgroup is summarized in [Table 3]. The ORR in the ramucirumab plus docetaxel arm and placebo plus docetaxel arm were 27.3% and 21.2%, respectively. The DCR (CR + PR + SD) for the ramucirumab plus docetaxel arm was 68.2% and that for the placebo plus docetaxel arm was 36.4%.
Table 3: Summary of best overall tumor responsea

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  Discussion Top


REVEL was a global randomized, double-blind, placebo-controlled, multicenter phase III study that compared ramucirumab plus docetaxel with placebo plus docetaxel in patients who had progressed during or after a first-line platinum-based chemotherapy for advanced or metastatic Stage IV NSCLC.[17] In the overall REVEL study, ramucirumab plus docetaxel improved survival when used as second-line treatment for patients with Stage IV NSCLC. Following this, ramucirumab in combination with docetaxel received regulatory approval for the treatment of patients with metastatic NSCLC who had experienced disease progression on or after platinum-based chemotherapy across multiple geographic locations.[20],[21]

In India, REVEL patients were treated at 9 investigative sites, with 55 randomized patients (22 patients in the ramucirumab plus docetaxel arm and 33 patients in the placebo plus docetaxel arm), which constituted the REVEL India subgroup. Here, we report the results of an exploratory analysis of safety and efficacy in the Indian patient REVEL subgroup. Although this subgroup analysis is not designed for comparison nor powered to demonstrate statistically significant improvement in survival, the Indian patients who received docetaxel plus ramucirumab combination treatment experienced a numeric prolongation of 8.2 months in OS over the placebo plus docetaxel arm. Ramucirumab plus docetaxel extended the PFS to 5.6 months from 1.5 months for Indian patients treated with placebo plus docetaxel. These results are consistent with the treatment effect observed in the overall intent to treat (ITT) population of the REVEL study.[17]

Patients with NSCLC who progress on first-line therapy have numerous therapeutic options. The 27.3% response rate reported for the ramucirumab plus docetaxel combination is comparable to the 35% response rate evidenced in a retrospective analysis from the oncology department at the Tata Memorial Hospital in Mumbai, India, of metronomic scheduling with paclitaxel using a continuous 80 mg/m2 weekly schedule.[22] Both response rates exceed the maximal ~20% rates achieved with immune checkpoint inhibitors. The Indian retrospective analysis reported a median PFS of 4 months and an estimated median OS of 7 months for patients with NSCLC treated with paclitaxel, both of which were numerically exceeded with ramucirumab plus docetaxel treatment presented here in the REVEL study.

Studies have reported that AEs, predominantly hematological in nature, are higher in Asian patients relative to Caucasian patients receiving docetaxel,[23],[24] with neutropenia being the predominant toxicity.[24] The cause for this increase could be differences in the pharmacokinetic profiles between the two races. In contrast, the safety data in these analyses showed that ramucirumab plus docetaxel was tolerated well by Indian patients, and treatment-emergent AEs rates were similar between treatment arms.

However, there are some limitations to this subgroup analysis. First, at the time of the REVEL study enrollment, the PD-L1 status of the patients was not evaluated as immune checkpoint inhibitors were not yet available as first-line therapy. Only the EGFR mutation status was evaluated, as evaluating the status of other biomarkers was beyond the scope of the study, at the time when the study was designed. The data here, therefore, need to be interpreted in this context. In addition, REVEL was not designed or powered to show significance in exploratory subgroups, and there was a relatively small number of patients in the Indian subgroup, suggesting that the data may not be representative of the Indian population as a whole. For example, each patient in the ramucirumab plus docetaxel arm contributed 4.5% to the frequency of an event which may have led to over-interpretation of the differences between event rates or patient characteristics in the two treatment arms.


  Conclusion Top


Our analysis adds to the India-specific literature, showing here that the survival benefits observed in the patients treated with ramucirumab plus docetaxel in the Indian subgroup are consistent with those seen in the overall ITT population of the REVEL study. Furthermore, the safety profile observed for the Indian subgroup was consistent with the safety profile for ramucirumab established in the global REVEL study and with the established safety profile for docetaxel. In clinical practice, ramucirumab may therefore be considered an important therapeutic option for Indian patients with metastatic NSCLC whose disease has progressed following platinum-based chemotherapy.

Financial support and sponsorship

This study was funded by Eli Lilly and Company Ltd. Prof. Prabhash has received research funding from Dr. Reddy's Laboratories Inc., Fresenius Kabi India Pvt. Ltd., Alkem Laboratories, Natco Pharma Ltd., BDR Pharmaceuticals Intl. Pvt. Ltd, and Roche Holding AG. All research grants were paid to the institution. Dr D'yachkova, Dr Pruthi, and Dr Puri are full time employees of, and stockholders in, Eli Lilly and Company.

Conflicts of interest

There are no conflicts of interest.



 
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    Figures

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    Tables

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