Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

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Lung Neoplasms

Carcinoma, Non-Small-Cell Lung

Carcinoma

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

Antineoplastic Agents

All Drugs and Chemicals

Lenvatinib

Protein Kinase Inhibitors

Enzyme Inhibitors

Participants received lenvatinib 24 mg orally, once daily continuously in each 28-day treatment cycle plus Best Supportive Care (BSC)

Participants received lenvatinib matched placebo orally, once daily continuously in each 28-day treatment cycle plus BSC

Lenvatinib matched placebo

Harish Dave

The purpose of this study is to compare the overall survival of patients receiving E7080 + Best Supportive Care (BSC) with those receiving placebo + Best Supportive Care.

This double-blind, placebo-controlled, multicenter, randomized Phase II study will consist of a 2-arm design, comparing E7080 + BSC (Arm 1) with placebo + BSC (Arm 2). Participants will be randomized in the ratio of 2:1 to receive either E7080 or placebo in a blinded manner.

A Study Comparing the Combination of the Best Supportive Care Plus E7080 Versus Best Supportive Care Alone, in Patients With Advanced Lung Cancer or Lung Cancer That Has Spread, Who Have Been Previously Treated, Unsuccessfully, With at Least 2 Different Treatments

A Phase II, Randomized, Double-Blind, Placebo-Controlled Study of Oral E7080 in Addition to Best Supportive Care (BSC) Versus BSC Alone in Patients With Locally Advanced or Metastatic Non-Squamous Non-Small Cell Lung Cancer Who Have Failed at Least Two Systemic Anticancer Regimens

OS was defined as the time from the date of randomization until the date of death from any cause.

An AE was defined as any untoward medical occurrence in a clinical investigation participant administered with an investigational product. A SAE was defined as any untoward medical occurrence that at any dose; resulted in death, was life-threatening (i.e., the subject was at a risk of death at the time of the event; this did not include an event that hypothetically might have caused death if it had been more severe), required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity or substantial disruption of the ability to conduct normal life functions, or was a congenital abnormality/birth defect. In this study, treatment emergent adverse events (TEAEs) (defined as an AE (serious/non-serious) that started/increased in severity on/after the first dose of study medication up to 30 days after the final dose of study medication) were assessed.

Event-free survival rate was calculated using Kaplan Meier estimations. The percentage of participants with event free survival up to 6 months and the corresponding 95% confidence interval were estimated for each treatment group. The data presented is based on the data cut-off date of 26 November 2013 while the study is still ongoing.

Event-free survival rate was calculated using Kaplan Meier estimations. The percentage of participants with event free survival up to 1 year and the corresponding 95% confidence interval were estimated for each treatment group. The data presented is based on the data cut-off date of 26 November 2013 while the study is still ongoing.

PFS was defined as the time from the date of the randomization until the date of first documented disease progression according to Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 or date of death from any cause (whichever occurred first), assessed based on investigator's assessment. Disease progression per RECIST v1.1 was defined as at least a 20% relative increase and 5 mm absolute increase in the sum of diameters of target lesions (taking as reference the smallest sum on study), recorded since the treatment started or the appearance of 1 or more new lesions. The data presented is based on the data cut-off date of 21 January 2014 while the study is still ongoing.

ORR, defined as the percentage of participants who had best overall response (BOR) of complete response (CR) or partial response (PR) as determined by investigator using RECIST 1.1. CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) had to have reduction in short axis to less than 10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. ORR = CR + PR. The data presented is based on the data cut-off date of 21 January 2014 while the study is still ongoing.

Response duration, defined as the time from the date of the first assessment demonstrating a CR or PR to the date of the first assessment demonstrating progressive disease or death, whichever occurred first. This is an investigator assessed outcome, measured using RECIST 1.1. CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) had to have reduction in short axis to less than 10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Response duration was summarized by including only subjects with events. The data presented is based on the data cut-off date of 21 January 2014 while the study is still ongoing.

The percentage of participants with CR, PR, or stable disease (SD) for greater than or equal to 12 weeks. CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) had to have reduction in short axis to less than 10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Stable disease was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on the study. The data presented is based on the data cut-off date of 21 January 2014 while the study is still ongoing.

The EORTC QLQ-C30 symptom score, a cancer specific self-reporting questionnaire was composed of 9-symptom scales assessing fatigue, nausea and vomiting, pain, dyspnea, insomnia, appetite loss, constipation, diarrhea and financial difficulties. All of the multi-item scales and single-item measures ranged in score from 0 to 100. For each domain and item, a linear transformation was applied to standardize the raw score to a range from 0 to 100, with a higher scale score representing a higher response level/ high level of symptomatology / problems. The data is presented as percentage of participants with EORTC QLQ-C30 symptom score achieving clinically significant deterioration on QOL. Participants were considered as deteriorated for a given symptom if the change in score from Baseline was 10 points or higher at any time point after Baseline. The data presented is based on the data cut-off date of 21 January 2014 while the study is still ongoing.

The EORTC module QLQ-LC13 symptom score was a self-reporting cancer-specific questionnaire composed of 13 questions incorporated into 1 multi-item scale designed to evaluate dyspnea and a series of single items assessing different types of pain, as well as, cough, hemoptysis, dysphagia, sore mouth, alopecia, and peripheral neuropathy. For each domain and item, a linear transformation was applied to standardize the raw score to a range from 0 to 100, with 100 representing the best possible function/QOL, and highest burden of symptoms for symptom domains and single items. The data is presented as percentage of participants with EORTC module QLQ-C13 symptom score achieving clinically significant deterioration on QOL. Participants were considered as deteriorated for a given symptom if the change in score from Baseline was 10 points or higher at any time point after Baseline. The data presented is based on the data cut-off date of 21 January 2014 while the study is still ongoing.

Blood samples were collected for lenvatinib PK analysis. Lenvatinib concentrations from sparse PK sampling were measured. The data is presented as mean nanograms per milliliter +/- Standard deviation of lenvatinib serum concentration.

Quintiles, Inc.

Eisai Inc.

Treatment emergent adverse events (TEAEs), defined as an AE (serious/non-serious) that started/increased in severity on/after the first dose of study medication up to 30 days after the final dose of study medication are presented in this section.

Participants received lenvatinib 24 mg orally, once daily continuously in each 28-day treatment cycle.

Participants received lenvatinib matched placebo orally, once daily continuously in each 28-day treatment cycle.

Lenvatinib Matched Placebo

Total

Age, Continuous

Sex: Female, Male

Treatment Emergent Non-Serious AEs

Treatment Emergent SAEs

Safety was analyzed in Safety Analysis Set defined as all subjects enrolled and randomized to treatment in study, except for those who (i) dropped out prior to receiving any study drug, or (ii) were without any safety assessment following the first dose of study drug.

Number of Participants With Treatment Emergent Non-serious Adverse Events (AEs) and Treatment Emergent Serious Adverse Events (SAEs)

The analysis was performed using the Intent-to-Treat Population, defined as all randomized subjects.

6-Month Survival Rate

1-year Survival Rate

Progression-Free Survival (PFS)

Overall Response Rate (ORR)

Overall Survival (OS)

The analysis was performed using subjects with events.

Response Duration (RD)

Disease Control Rate (DCR)

Appetite Loss (N=82, 39)

Constipation (N=82, 40)

Diarrhea (N=81, 40)

Dyspnea (N=82, 40)

Insomnia (N=82, 40)

Nausea and Vomiting (N=82, 40)

Pain (N= 82, 40)

Fatigue (N= 82, 40)

Financial Difficulties (N= 81, 40)

The Percentage of Participants With The European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 Symptom Scores Achieving Clinically Significant Deterioration on Quality of Life (QOL)

Alopecia (Hair Loss) (N= 80, 39)

Dysphagia (Trouble Swallowing) (N= 80, 39)

Haemoptysis (Coughing Up Blood) (N=80, 39)

How Much Cough (N=80, 39)

Medicine For Pain (N=43, 21)

Pain In Arm Or Shoulder (N=80, 39)

Pain In Chest (N=80, 39)

Pain In Other Parts Of Body (N=79, 39)

Peripheral Neuropathy-Tingling Hands/Feet(N=80,39)

Short Of Breath When Climbed Stairs (N=80, 39)

Short Of Breath When Rested (N=80, 39)

Short Of Breath When Walked (N=80, 39)

Sore Mouth Or Tongue (N=80, 39)

The Percentage of Participants With The European Organization for Research and Treatment of Cancer (EORTC) Module QLQ-LC13 (Lung Cancer 13) Symptom Scores Achieving Clinically Significant Deterioration on QOL

Cycle 1 Day 1 (0.5 to 4 hours postdose); N=47

Cycle 1 Day 1 (6 to 10 hours postdose); N=46

Cycle 1 Day 15 (Pre-dose); N=43

Cycle 1 Day 15 (0.5 to 4 hours postdose); N=44

Cycle 1 Day 15 (6 to 10 hours postdose); N=39

Cycle 2 Day 1 (Pre-dose); N=42

Cycle 2 Day 1 (2 to 12 hours postdose); N=41

Cycle 3 Day 1 (Pre-dose); N=34

Cycle 3 Day 1 (2 to 12 hours postdose); N=31

Cycle 4 Day 1 (Pre-dose); N=29

Cycle 4 Day 1 (2 to 12 hours postdose); N=27

The analysis was performed using the pharmacokinetic (PK) analysis set defined as all subjects who received at least one dose of study drug and had evaluable PK data.

Spots Global Cancer Trial Database for lenvatinib matched placebo