Safety and Efficacy of Buparlisib (BKM120) in Patients With Untreated Squamous Non-small Cell Lung Cancer

Overall response is the number of participants who had a complete response (CR) or a partial response (PR) based on local investigator's assessment of RECIST criteria. Per RECIST: CR, all detectable tumor has disappeared; PR, a >=30% decrease in the sum of the longest dimensions of the target lesions (TLs) taking as a reference the baseline sum, no worsening of non-TLs, and no new lesions; Progressive disease (PD), a >=20% increase in TLs, clearly worsening of non-TLs, or emergence of new lesions; Stable Disease (SD), small changes that do not meet previously given criteria.

Overall survival (OS) time was measured from the start of study drug to the date of death due to any cause. If a patient was not known to have died, survival was censored at the date of last contact. Data was collected post treatment every 6 weeks until approximately 75% of patients have reached the survival endpoint (Phase I + Phase II).

Time to overall response (TTR) is defined as the time from the date of first drug intake in Phase Ib and from the date of randomization in Phase II to the date of first documented response. TTR will primarily be listed.

Assessments consisted of recording all AEs and serious adverse events (SAEs), the regular monitoring of hematology, blood chemistry, vital signs, physical condition and body weight.

Quality of life (QoL) is evaluated using EORTC QLQ-C30 and QLQ-LC-13 scale. QLQ-L30 is composed of 30 items, whose responses range from 0 to 4. The QLQ-LC13 is used in conjucntion with the QLQ-C30 and provides information on an additional 13 items specifically relating to lung cancer. It incorporates one multi-item scale to assess dyspnea and a series of single-item scale to assess pain, coughing, sore mouth, dysphagia, peripheral neuropathy, alopecia, and haemoptysis. All the multi-item scales and single-item measures range in score from 0 to 100. A high scale score represents a higher response level. Thus a high score for a functional scale represents a high / healthy level of functioning, a high score for the global health status / QoL represents a high QoL, but a high score for a symptom scale / item represents a high level of symptomatology / problems.

Time to definitive 10% deterioration in the global health status / QoL, physical functioning, emotional functioning, social functioning, and lung cancer symptoms scales will be assessed in the two treatment arms.

Pharmacokinetics of buparlisib will be investigated in order to investigate any unexpected impact of carboplatin and paclitaxel therapy on the pharmacokinetics of buparlisib. For this purpose, plasma samples will be collected during phase II of the trial. In one set of the population (N=40) samples will be collected according to a sparse sampling strategy over the entire course of the treatment, to allow a proper estimate of the pharmacokinetic parameters. In addition, trough samples should be collected, for the whole population, for measurement of buparlisib/placebo. These additional samples will allow investigating potential PK/PD relationships for various therapeutic or adverse outcome in the whole study population.

Duration of overall response (DR) is defined as the elapsed time between the date of first documented response and the following date of event defined as the first documented progression or death due to underlying cancer. DR will primarily be listed. DR may be described using Kaplan-Meier curves and any related statistics if relevant and will be presented by treatment group in phase II. These analyses will be performed on the responder subset, i.e. patients with a confirmed complete response (CR) or partial response (PR).

Buparlisib concentrations and model-based PK derived parameters