Atezolizumab and pembrolizumab in triple-negative breast cancer: a meta-analysis

ABSTRACT

Background

The approval of anti-PD-L1 drugs, including atezolizumab/pembrolizumab in triple-negative breast cancer (TNBC), potentially improveme treatment regimens available for TNBC.

Methods

We conducted a meta-analysis to review the efficacy of atezolizumab/pembrolizumab for the treatment of TNBC in both the adjuvant and neoadjuvant settings. We calculated standardized mean difference (SMD) for the associations of progression-free survival (PFS) and overall survival (OS) and odds ratios (ORs) to estimate objective response rate (ORR) and pathological complete response (pCR), using 95% confidence intervals (CIs).

Results

Six clinical trials comprising 3612 patients were included. For adjuvant therapies, the ORR (OR = 1.26, P = 0.04) of atezolizumab/pembrolizumab plus chemotherapy was higher in the intention to treat (ITT) arms than the placebo groups in TNBC. A positive effect size was found for PFS in the ITT arms (d = 1.55, P < 0.001). The atezolizumab plus chemotherapy group had a positive effect size for OS compared to control groups (d = 0.52, P < 0.001). In the neoadjuvant setting, patients in ITT arms had higher pCR rates than the control groups (OR = 1.61, P = 0.001).

Conclusion

We collate evidence of atezolizumab/pembrolizumab as viable therapeutics among patients with TNBC with PD-L1 subgroups deriving higher benefits.

PLAIN LANGUAGE SUMMARY

Immune checkpoint inhibitors (ICI), atezolizumab and pembrolizumab, have received approval for patients with triple-negative breast cancer (TNBC) expressing PD-L1. Thus far, it has only been approved for patients with unresectable locally advanced or metastatic TNBC. With the IMpassion 130 and KEYNOTE-355 trials introducing the immunotherapy era for TNBC, ongoing trials have started exploring the outcomes of the ICIs in early-stage TNBC in combination. Recently, the ICIs have demonstrated positive efficacy outcomes in neoadjuvant settings. Both the ICIs have shown a safe profile in terms of adverse events. The recent advances made by clinical trials indicate promising results for early-stage and advanced/metastatic TNBC. However, there is a need to harmonize and explore biomarkers and endpoints in the ongoing clinical trials to enhance patient treatment protocols. As TNBC is an aggressive subtype, exploring beyond the PD-L1 positive subgroup is necessary to expand the target population receiving ICIs for TNBC.

KEYWORDS:

• Triple-negative breast cancer
• pembrolizumab
• atezolizumab
• chemotherapy
• anti-PD-L1
• biomarkers
• targeted therapies
• development of novel drugs

Article highlights

• We reviewed six clinical trials in any stage of triple-negative breast cancer (TNBC) for patients receiving immune checkpoint inhibitors atezolizumab or pembrolizumab.

• Patients received any of the two immunotherapeutic agents as first-line, second-line, or beyond in early-stage and late-stage TNBC.

• We included three adjuvant trials, namely IMPassion130, IMpassion131, KN355, and three neoadjuvant trials NeoTRIP, IMpassion031, KN522, due to their availability of data that reported patient outcomes for atezolizumab or pembrolizumab.

• There was a statistically significant improvement in the efficacy of atezolizumab or pembrolizumab combined with chemotherapy compared to chemotherapy alone, with further improvement in particular PD-L1 positive subgroups, particularly in the PD-L1+ subgroup.

• Though significant, our findings ought to be used with caution despite employing a fairly large number of meta-analyzed patients (N= 3612).

• Selecting the most effective chemotherapeutic agent for combination with chemotherapy is necessary and exploring selective outcomes in early-stage TNBC.

• Other exploratory biomarkers (e.g. gene signatures, tumor-infiltrating lymphocytes) should be considered to improve and guide treatment and effectiveness in patients with TNBC.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Supplementary material

Supplemental data for this article can be accessed here.

Additional information

Funding

The authors have no funding to report.