Alisertib in Adults With Nonhematological Malignancies, Followed by Alisertib in Lung, Breast, Head and Neck or Gastroesophageal Malignancies

PFS was defined as the time from randomization (or the first dose of study treatment for non-randomized studies) to the first documentation of objective tumor progression or to death due to any cause, whichever occurred first. Tumor progression as per RECIST 1.1 was defined as at least 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this included the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of 1or more new lesions is also considered progression.

Time in days from start of study treatment to first documentation of objective tumor progression. Tumor progression as per RECIST 1.1 was defined as at least 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of 1or more new lesions is also considered progression.

Time in days from the first documentation of objective tumor response to objective tumor progression or death due to any cancer. Duration of tumor response=(the date of the first documentation of objective tumor progression or death due to cancer minus the date of the first CR or PR that was subsequently confirmed plus 1). CR: complete disappearance of all target lesions and non-target disease, except nodal disease; all nodes decreased to normal; no new lesions. PR: >=30% decrease under baseline of the sum of diameters of all target lesions; no unequivocal progression of non-target disease; no new lesions. Tumor progression: >=20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study); absolute increase of >=5 mm; appearance of >=1 new lesions is also considered progression. DOR calculated for the subgroup of participants with objective response.

An adverse event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (example, a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug. A treatment-emergent adverse event (TEAE) is defined as an adverse event with an onset that occurs after receiving study drug. A serious adverse event (SAE) is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; or congenital anomaly; or a medically important event.

Maximum observed plasma concentration (Cmax) is the peak plasma concentration of a drug after administration, obtained directly from the plasma concentration-time curve.

Tmax: Time to reach the maximum plasma concentration (Cmax), equal to time (hours) to Cmax.

Area under the plasma concentration-time curve during a dosing interval, where tau is the length of the dosing interval.

Terminal phase elimination half-life (T1/2) is the time required for half of the drug to be eliminated from the plasma.

Rac was estimated as a ratio of AUC (0-tau) at Day 7 and AUC (0-tau) at Day 1. Area under the plasma concentration-time curve during a dosing interval, where tau is the length of the dosing interval.

Peak to trough ratio was estimated as a ratio of Cmax at Day 7 and the minimum observed plasma concentration (Ctrough) of alisertib at Day 7. Cmax is the peak plasma concentration of a drug after administration, obtained directly from the plasma concentration-time curve. Ctrough is the minimum plasma concentration of a drug after administration, obtained directly from the plasma concentration-time curve.

CL/F is apparent clearance of the drug from the plasma, calculated as the drug dose divided AUC(0-tau), expressed in liter per hour (L/hr).

In SCLC,chemo-sensitive/resistant population were analyzed;in breast cancers,ER2 and ER2 status were analyzed.HR+ =estrogen receptor-positive or progesterone receptor-positive. HER+ =human epidermal growth factor receptor 2 (HER2). Triple negative =negative for estrogen receptors, progesterone receptors, and HER2.Clinical response according to RECIST version 1.1. CR:complete disappearance of all target lesions,non-target disease,except nodal disease;all nodes decrease to normal (short axis <10 mm);no new lesions. PR:>=30% decrease under baseline of the sum of diameters of all target lesions (SLD);short axis was used in the sum for target nodes,longest diameter used in the sum for all other target lesions;no unequivocal progression of non-target disease;no new lesions. Progressive Disease (PD): >=20% rise in SLD from the smallest value on study;unequivocal progression of existing non-target lesions. Stable Disease (SD):Neither sufficient shrinkage for PR nor sufficient increase for PD.