A Study of Abemaciclib (LY2835219) in Participants With Stage IV Squamous Non-small Cell Lung Cancer

PFS was defined as time from the date of randomization to the date of investigator-determined disease progression as defined by Response Evaluation Criteria in Solid Tumors (RECIST v1.1) or death from any cause. Progressive disease (PD) was defined as at least a 20% increase in the sum of the longest diameters (LD) of target lesions, with reference the smallest sum on study and an absolute increase of at least 5mm, or unequivocal progression of non-target lesions, or 1 or more new lesions. If a participant was not known to have died or have objective progression, PFS time will be censored at the day of their last radiographic tumor assessment (if available) or date of randomization if no post baseline radiographic assessment is available.

Time frame: Baseline to Objective Progression or Death from Any Cause ( Up To 6 Months)

Population: All participants according to the treatment group to which they were randomized. Participants censored: Abemaciclib=19 and Docetaxel= 15.

The EQ-5D-5L is a standardized instrument for use as a measure of self-reported health status. Overall self-rated health was measured with a vertical 20 cm visual analog scale (VAS) anchored at 0 (worst health) and ranged through 100 (best health). Between-group differences in regression-predicted change from baseline score were estimated for VAS scores. MMRM models included independent variables treatment, visit, treatment\*visit, and baseline score. Group-level negative change from baseline indicated group improvement.

Time frame: Baseline to Measured Progressive Disease (Up To 6 Months)

Population: All randomized participants for cycles which at least 25% of participants in each arm have a score.The EQ-5D-5L population included all randomized participants who completed at least 1 baseline assessment followed by at least 1 EQ-5D-5L assessment after Cycle 1 (for example, a completed EQ-5D-5L questionnaire at Cycle 2 Day 1 or later).

There are 5 response levels on a good-to-bad continuum of 1-5 corresponding to none, slight, moderate, severe, and extreme/unable to.The EuroQol-developed crosswalk method was used to convert the EQ-5D-5L,using UK weights,health dimensions(mobility,self-care,usual activities,pain/discomfort, and anxiety/depression) into a single index value;the dimensions are not separately scored.The index is marked missing when ≥1 dimensions are missing.The index scores for the response patterns were anchored on full health to dead with negative values assigned to response patterns/health states considered worse than death.The best pattern is assigned the index value of 1.0; the worst pattern is assigned an index value of -0.594. Between-group differences in regression-predicted change from baseline score were estimated for the index .MMRM models included independent variables treatment, visit, treatment\*visit, and baseline score.Group-level negative change from baseline indicated group improvement.

Time frame: Baseline to Measured Progressive Disease (Up To 6 Months)

Population: All randomized participants for cycles which at least 25% of participants in each arm have a score.The EQ-5D-5L population included all randomized participants who completed at least 1 baseline assessment followed by at least 1 EQ-5D-5L assessment after Cycle 1 (for example, a completed EQ-5D-5L questionnaire at Cycle 2 Day 1 or later).

MDASI-LC included 33 items:6 interference and 27 symptom(3 lung-cancer (LC),8 brain tumor (BT),and 3 study-specific(headache,diarrhea, and rash).Analyzed endpoints were 9 constructs:3 single-items (headache,diarrhea,and rash) and 6 composites(interference+core,LC,core+LC,BT, and core+LC worst 5 baseline).Data for all 9 constructs were collected by an 11-point numeric rating scale anchored at 0(not present or does not interfere) and 10(as bad as you can imagine or interfered completely).The measurement range was 10 (maximum score-minimum score). Between-group difference in regression-predicted change from baseline were estimated for each specified construct. MMRM models included independent variables treatment,visit, treatment\*visit,and baseline score. Group-level negative change from baseline indicated group improvement.

Time frame: Baseline through End of Study (Up To 6 Months)

Population: All randomized participants for cycles which at least 25% of participants in each arm have a score.MDASI-LC population included all randomized participants who completed at least 1 baseline assessment followed by at least 1 MDASI-LC assessment after Cycle 1 (for example, a completed MDASI-LC questionnaire at Cycle 2 Day 1 or later)

OS was defined as the time from randomization to the date of death due to any cause. For each participant who is not known to have died as the data inclusion cutoff date for overall survival analysis, OS time was censored on the last date the participant is known to be alive.

Time frame: Baseline to Date of Death from Any Cause (Up To 28 Months)

Population: All participants according to the treatment group to which they were randomized. Participants censored: Abemaciclib=35 and Docetaxel= 17.

DCR is the percentage of randomized participants who achieved a complete response, partial response or stable disease using Response Evaluation Criteria In Solid Tumors (RECIST v1.1) criteria. Complete response (CR) is defined as the disappearance of all target and non-target lesions, and no appearance of new lesions. Partial response (PR) is defined as at least a 30% decrease in the sum of longest diameters (LD) of target lesions (taking as reference the baseline sum LD), no progression of non-target lesions and no appearance of new lesions. Stable disease was neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD for target lesions, no progression of non-target lesions, and no appearance of new lesions.

Time frame: Baseline through Measured Progressive Disease or Death Due to Any Cause (Up To 6 Months)

Population: All randomized participants.

Overall response was defined as the percentage of randomized participants achieving a best overall response (BoR) of complete response (CR) or partial response (PR) using Response Evaluation Criteria In Solid Tumors (RECIST v1.1) criteria. Participants with unevaluable or unknown response status are considered nonresponders. Complete response (CR) is defined as the disappearance of all target and non-target lesions and no appearance of new lesions. Partial response (PR) is defined as at least a 30% decrease in the sum of the longest diameters (LD) of target lesions (taking as reference the baseline sum LD), no progression of non-target lesions and no appearance of new lesions.

Time frame: Baseline to Objective Progression (Up To 6 Months)

Population: All randomized participants.

Pharmacokinetics (PK): Clearance of Abemaciclib

Time frame: Cycle (C) 1 Day (D) 1: Pre-dose; C1D8: 4 and 7 hr Post-dose; C2D1: Pre-dose and 3 hr Post-dose; C3 and C4 D1:Pre-dose

Population: All participants who received abemaciclib and had evaluable PK data.

PK: Volume of Distribution of Abemaciclib

Time frame: Cycle (C) 1 Day (D) 1: Pre-dose; C1D8: 4 and 7 hr Post-dose; C2D1: Pre-dose and 3 hr Post-dose; C3 and C4 D1:Pre-dose

Population: All participants who received Abemaciclib and had evaluable PK data.

Worsening of ECOG performance status is the duration from randomization to ECOG PFS of \>/=2. Participants without an ECOG PFS \>/=2 are censored at last adequate post baseline ECOG Performance Status or randomization date (whichever is last). The ECOG Performance Status:0 - Fully active, able to carry on all pre-disease performance without restriction,1 - Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, 2 - Ambulatory and capable of all selfcare but unable to carry out any work activities. Up and about more than 50% of waking hours,3 - Capable of only limited selfcare, confined to bed or chair more than 50% of waking hours, 4 - Completely disabled. Cannot carry on any selfcare. Totally confined to bed or chair, 5 - Dead

Time frame: Randomization to ECOG PFS of >/=2 (Up To 11.5 Months)

Population: All randomized participants. Participants censored: Abemaciclib =93 and Docetaxel= 43.