Pembrolizumab (18) – Keytruda®

• Clinical trials
  • In the KEYNOTE 355 trial, pembrolizumab in combination with chemotherapy was compared with placebo in combination with chemotherapy.

a) Pembrolizumab in combination with nab-paclitaxel or paclitaxel for the treatment of adults with locally recurrent, unresectable or metastatic triple-negative breast cancer with PD-L1-expressing tumours (Combined Positive Score [CPS] ≥ 10) who have not previously received chemotherapy for the treatment of metastatic disease

• mortality
  • In the KEYNOTE 355 trial, overall survival was defined as the time from randomisation to death, regardless of the underlying cause.
  • For the endpoint of overall survival, a statistically significant difference was observed in favour of pembrolizumab in combination with nab-paclitaxel or paclitaxel.
  • The extent of the prolongation in overall survival achieved is considered a significant improvement.
• Morbidity – Progression-free survival (PFS)
  • In the KEYNOTE 355 trial, PFS was defined as the period from randomisation to the first documented instance of disease progression or death from any cause, whichever occurred first.
  • There was a statistically significant prolongation of PFS in favour of pembrolizumab in combination with nab-paclitaxel or paclitaxel.
  • The PFS endpoint is a composite endpoint comprising endpoints from the categories of mortality and morbidity.
  • The morbidity component was not assessed on the basis of symptoms, but exclusively by means of imaging procedures (radiologically confirmed disease progression according to the RECIST 1.1 criteria).
• quality of life
  • Health-related quality of life was assessed in the KEYNOTE 355 trial using the functional scales of the EORTC QLQ-C30 and EORTC QLQ-BR23.
  • Quality of life was operationalised as time to first deterioration. A decrease in the score of ≥ 10 points compared with baseline was considered a clinically relevant deterioration.
  • No statistically significant difference was observed between the treatment arms in the functional scales of the EORTC QLQ-C30.
  • Similarly, no statistically significant differences were found for the functional scales of the EORTC QLQ-BR23 (‘body image’, ‘sexual activity’ and ‘future prospects’). No usable data are available for the ‘sexual enjoyment’ scale.
  • With regard to quality of life, therefore, no overall advantage or disadvantage of pembrolizumab in combination with nab-paclitaxel or paclitaxel compared with nab-paclitaxel or paclitaxel alone can be identified.
• Side effects
  • Total adverse events (AEs)
  • In the KEYNOTE 355 trial, AEs occurred in almost all patients enrolled in both treatment arms.
  • Serious adverse events (SAEs), severe adverse events (CTCAE grade ≥ 3) and discontinuation due to AEs
  • No statistically significant difference was observed between the treatment arms for the endpoints of SAE, severe AEs and discontinuation due to AEs.
  • Specific adverse events
  • For the specific AEs diarrhoea (PT, AEs), dysgeusia (PT, AEs) and gastrointestinal disorders (SOC, AEs), there was a statistically significant difference to the disadvantage of pembrolizumab in combination with nab-paclitaxel or paclitaxel in each case.
  • Taking an overall view of the results regarding side effects, neither an advantage nor a disadvantage can be identified for pembrolizumab in combination with nab-paclitaxel or paclitaxel compared with nab-paclitaxel or paclitaxel alone. In detail, disadvantages are evident for the specific AEs.
• Overall assessment
  • For the benefit assessment of pembrolizumab in combination with nab-paclitaxel or paclitaxel for the treatment of locally recurrent, unresectable or metastatic triple-negative breast cancer with PD-L1-expressing tumours (Combined Positive Score [CPS] ≥ 10) in adults who have not previously received chemotherapy for the treatment of metastatic disease, data are available from the KEYNOTE 355 trial for the relevant patient population regarding mortality, morbidity, quality of life and side effects.
  • For the endpoint of overall survival, a statistically significant difference in favour of pembrolizumab in combination with nab-paclitaxel or paclitaxel is observed. The extent of the effect is assessed as a marked improvement.
  • In the morbidity category, within the symptom scales of the EORTC QLQ-C30, a statistically significant difference to the disadvantage of pembrolizumab in combination with nab-paclitaxel or paclitaxel was observed for the diarrhoea scale. Within the symptom scales of the EORTC QLQ-BR23, a statistically significant advantage was found in favour of pembrolizumab in combination with nab-paclitaxel or paclitaxel on the ‘arm symptoms’ scale. Overall, no relevant difference was observed with regard to morbidity.
  • In the functional scales of the EORTC QLQ-C30 and the EORTC QLQ-BR23 (‘body image’, ‘sexual activity’ and ‘future prospects’), no statistically significant differences were observed between the treatment arms. No usable data are available for the ‘sexual enjoyment’ subscale. With regard to quality of life, therefore, no overall advantage or disadvantage of pembrolizumab in combination with nab-paclitaxel or paclitaxel can be identified.
  • An overall review of the results on side effects reveals neither an advantage nor a disadvantage for pembrolizumab in combination with nab-paclitaxel or paclitaxel compared with nab-paclitaxel or paclitaxel alone. In detail, disadvantages are evident in terms of specific adverse events.
  • Overall, there is a clear advantage in terms of overall survival, no relevant differences in morbidity and quality of life, no relevant differences in the overall rates of adverse events, and, in detail, disadvantages regarding specific adverse events. With regard to side effects, no relevant difference is observed overall.
  • In the overall assessment, the additional benefit is quantified in this case, taking into account the uncertainties described and the magnitude of the effect on overall survival. For pembrolizumab in combination with nab-paclitaxel or paclitaxel in adults with locally recurrent, unresectable or metastatic triple-negative breast cancer with PD-L1-expressing tumours (Combined Positive Score [CPS] ≥ 10) who have not previously received chemotherapy for the treatment of metastatic disease, a considerable additional benefit is identified.

b) Pembrolizumab in combination with a chemotherapy other than nab-paclitaxel or paclitaxel for the treatment of adults with locally recurrent, unresectable or metastatic triple-negative breast cancer with PD-L1-expressing tumours (Combined Positive Score [CPS] ≥ 10) who have not previously received chemotherapy for the treatment of metastatic disease

• No data are available to enable an assessment of additional benefit. Additional benefit is therefore not proven.

Courtesy translation only, please refer to the German original.