Date of first round report: 1 September 2016 Date of second round report: 30 January 2017



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Results for the primary efficacy outcome

Primary efficacy endpoint Progression-free survival investigator assessment

Due to rapid accrual, a total of 195 events (82% of the total planned final PFS events expected (SAP specified 60%)) were included in the interim analysis. At the data cut-off date of 05 December 2014, 102 (29.4%) out of 347 patients in the palbociclib plus fulvestrant arm and 93 (53.4%) out of 174 patients in the placebo plus fulvestrant arm had experienced disease progression or had died.

  • median PFS 9.2 months (95% CI: 7.5, not estimable) for palbociclib and fulvestrant arm 3.8 months (95% CI: 3.5, 5.5) for placebo plus fulvestrant;

  • observed HR was 0.422 (95% CI: 0.318, 0.560; stratified 1-sided p-value <0.000001) in favour of palbociclib plus fulvestrant;

Of 70.6% of patients in the palbociclib plus fulvestrant arm and 46.6% in the placebo plus fulvestrant arm were censored in the investigator-assessed PFS analysis, the majority were still in follow-up for disease progression: (65.4%) patients in the palbociclib plus fulvestrant arm and 40.2% the placebo plus fulvestrant arm.
16 March 2015 cut-off data

As of the 16 March 2015 data cutoff date for the updated analysis, 259 patients with progression or death have been reported:

    • 145 (41.8% of 347 patients) were from the palbociclib plus fulvestrant arm and 114 (65.5% of 174 patients) were from the fulvestrant arm, respectively.

    • The median duration of follow-up for both arms was 8.9 months (95% CI: 8.7, 9.2 for the treatment arm; 8.3, 9.4 for the control).

Among the censored patients, 177 and 48 patients in the palbociclib plus fulvestrant arm and the placebo plus fulvestrant arm, respectively, were still in follow-up for disease progression.

  • Median PFS was 9.5 months (95% CI: 9.2-11.0) in the palbociclib plus fulvestrant arm

  • and 4.6 months (95% CI: 3.5, 5.6) in the placebo plus fulvestrant arm;

  • HR was 0.461 (95% CI: 0.360, 0.591; 1-sided p<0.000001) in favour of palbociclib plus fulvestrant.
23 October 2015 cut-off data

As of the 23 October 2015 data cutoff date for this updated analysis, a total of 333 patients with objective progression or death have been reported:

  • 200 (57.6% of 347 patients) were from the palbociclib plus fulvestrant arm and 133 (76.4% of 174 patients) were from the fulvestrant arm;

  • median duration of follow-up was 15.8 months (95% CI: 15.5,16.2) for the palbociclib plus fulvestrant arm and 15.3 months (95% CI: 15.0, 15.9) for the placebo plus fulvestrant arm

Comment: A 95% CI has been provided for the duration of follow-up rather than a range. Given the short accrual time, presenting the range is unlikely to alter the outcomes or understanding of the data but it would normally be a range that is presented as follow up is an actual measurement not an estimate.

Table 15: Study A5481023 Investigator-assessed patient disposition as at the cut-off 23 October 2015



Among the censored patients in the palbociclib plus fulvestrant arm (2 patients were not treated), 109 (31.4%) and were still being followed up for disease progression as of 23 October 2015, while 25 patients (14.4%) were still in follow up in the comparator arm. Censoring for reasons other than progression was similar between the arms, with similar percentages of protocol deviations across the two arms:



  • median PFS was 11.2 months (95% CI: 9.5-12.9) in the palbociclib plus fulvestrant arm and 4.6 months (95% CI: 3.5-5.6) in the placebo plus fulvestrant arm;

  • HR (stratified analysis) was 0.497 (95% CI: 0.398-0.620; stratified 1-sided p<0.0001) in favour of palbociclib plus fulvestrant treatment.

Comment: These results demonstrate a clinically relevant and statistically significant improvement in progression-free survival. The statistically significant improvement in the PFS results are robustly demonstrated at all 3 time points for which data are presented.

Figure 10: Kaplan Meier plot for PFS (Investigator assessment, ITT population – Study A5481023 as of 23 October 2015)




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