Background and Importance Recent studies have established the influence of the immune system on disease progression in triple negative breast cancer (TNBC) patients.
Aim and Objectives To determine if pembrolizumab and atezolizumab can be considered equivalent first-line therapeutic alternatives (ATE) by using a common comparator, for patients with locally recurrent unresectable or metastatic unresectable TNBC in adults whose tumours express PD-L1 and who have not received prior chemotherapy.
Material and Methods A bibliographic search was conducted to select phase III randomised clinical trials of first-line treatments for TNBC. The indirect comparison was performed with the Bucher method. The variable selected to determine clinical equivalence was progression-free survival (PFS), due to the lack of maturity with respect to the overall survival variable. The maximum acceptable difference as a clinical non-inferiority standard Delta (D), and its inverse were set at 0.65 and 1.54, respectively. They were established by ESMO-Magnitude of Clinical Benefit Scale.
To establish the positioning, we applied the criteria of the guide on therapeutic alternatives.
Results According to the clinical studies reviewed, a potential therapeutic equivalent to pembrolizumab, atezolizumab combined with nab-paclitaxel (IMpassion 130) was identified for the treatment of TNBC whose tumours overexpress PD-L1≥1% and who have not received prior chemotherapy for their metastatic disease. Although in our case (KEYNOTE-355), the PD-L1≥10 subgroup was considered the reference subgroup for the study, we have data from the PDL1≥1 subgroup in patients treated with pembrolizumab in combination with chemotherapy that allow us to make the comparison.
After applying the Bucher method, a HR=0.85 (95% CI 0.63 to 1.16) was obtained for pembrolizumab + chemoterapy versus atezolizumab + nab-paclitaxel. Considering the standard delta established, this is a probable clinical equivalence. We have to resort in this case to Shakespeare’s calculator which states that there is a 4.25% probability that the value is below 0.65. Since this is a probability of less than 17%, we can conclude that these are equivalent therapeutic alternatives.
Conclusion and Relevance Pembrolizumab and atezolizumab could be considered ATE, however, recent studies such as the Impassion 131 bring a great deal of uncertainty to this determination.
Conflict of Interest No conflict of interest.
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