Randomized Phase II Trial of Letrozole With or Without Dasatinib as First and Second-line Treatment for Hormone Receptor-positive, HER2-negative Post-menopausal Breast Cancer That is Unresectable, Locally Recurrent or Metastatic

CBR=participants with complete response (CR) + participants with partial response (PR) + participants with stable disease (SD) for a length of time greater than, equal to 6 months. CR= Disappearance of all target lesions. No new lesions. PR= At least a 30% decrease in the sum of the longest diameter (LD) of target lesions taking as reference the baseline sum LD. SD= Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD) taking as reference the smallest sum LD since the treatment started. Physical examination,radiological assessment, and bone scans (if applicable) were used to assess outcome.

Time frame: First dose of study drug to last dose plus 7 days, up to study completion (approximately 6 years)

Population: Evaluable Population was defined as all treated participants who met the protocol-specified efficacy analyses requirements and who received at least 1 dose of randomized study drug. Participants presented in the treatment arm to which they were originally randomized.

PFS was measured in months. Progression=At least a 20% increase in the sum of LD of target lesions taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. Study initiated 2008 and completed 2014.

Time frame: Day 1 to Study Completion (approximately 6 years)

Population: ITT population includes all participants enrolled in the study. The participants were analyzed as per the treatment arm to which they were originally randomized.

Time to TTF was measured in months. The number of participants with events (PD or off treatment due to any reason) was evaluated. The first PD was defined as the event for cross over participants in the single- agent letrozole treatment arm to add dasatinib to their regimen.

Time frame: First dose of study drug to last dose plus 7 days, up to study completion (approximately 6 years)

Population: ITT population: All participants enrolled in the study.

AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization.

Time frame: First dose of study drug to last dose plus 30 days, up to study completion (approximately 6 years)

Population: All participants who received at least one dose of study drug were summarized. The participants were analyzed as per the treatment arm to which they were originally randomized.

CR= Disappearance of all target lesions. No new lesions. PR= At least a 30% decrease in the sum of the longest diameter (LD) of target lesions taking as reference the baseline sum LD. SD= Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD) taking as reference the smallest sum LD since the treatment started. Progression (PD): At least a 20% increase in the sum of LD of target lesions taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions.

Time frame: First dose of study drug to last dose plus 7 days, up to study completion (approximately 6 years)

Population: All treated participants who met the protocol-specified efficacy analyses requirements and who received at least 1 dose of study drug were analyzed. The participants are analyzed as per the treatment arm to which they were originally randomized.

Participants in single-agent letrozole treatment arm who developed progressive disease, could continue letrozole, and add dasatinib to their treatment regimen. CBR=participants with CR + participants with partial response (PR) + participants with SD for a length of time ≥6 months divided by the total number of participants (%). CR= Disappearance of all target lesions. No new lesions. PR= At least a 30% decrease in the sum of the longest diameter (LD) of target lesions taking as reference the baseline sum LD. SD= Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD) taking as reference the smallest sum LD since the treatment started. PD=At least a 20% increase in the sum of LD of target lesions taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions.

Time frame: First dose of study drug to last dose plus 7 days, up to study completion (approximately 6 years)

Population: Participants who changed their treatment regimen from single-agent letrozole to letrozole + dasatinib during the study.

Progression=At least a 20% increase in the sum of LD of target lesions taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. ITT population: from time of first enrollment to first PD for all ITT participants.

Time frame: At 6 months and at 12 months

Population: ITT population=Includes all participants registered on the study. n= number at risk