Does ethnicity matter in chemotherapy for breast cancer?

The efficacy of pertuzumab with docetaxel in neoadjuvant treatment of HER2 positive breast cancer patients has been proven in NEOSPHERE trial (1). However, since only 25% of patients participating in that trial had Asian origins, it is not completely safe to extrapolate its results to Asian population. It has been shown that ethnic differences in toxicity profile exist between Asian and Caucasian patients given adjuvant docetaxel and cyclophosphamide. And since those differences can reach important numbers (e.g., grade ≥3 neutropenia in 5% of Caucasians and 30% of Asians) (2), we have to be cautious while implementing results of one trial to another population (3).

The PEONY trial fills therefore an important data gap giving us the results of double-blind phase III trial of efficacy and safety of pertuzumab and docetaxel in Asian patients with early and locally advanced breast cancer (4).

The compared treatment regimens in PEONY trial were similar to two of the four arms of the NEOSPHERE trial with one important difference: pertuzumab was given also in postoperative period. The primary endpoint was complete pathologic response (ypT0/ypTis, ypTN0) evaluated in surgical specimen of operated patients by an independent commission.

The independent specimen evaluation is one of the strongest aspects of the PEONY trial: it has not been used in the NEOSPHERE trial. On the other hand, some data from experimental arm require further analysis: adverse events grade 3 and up occurred in 48.6%, diarrhea was fairly common (38.5%) and grade 2 severe diarrhea occurred in every tenth patient. There was one death in the experimental arm due to a suicide; the authors state that it was not related to pertuzumab, trastuzumab or docetaxel treatment but the effects on those treatments on the occurrence of suicidal thoughts is not well studied.

The primary endpoint of the PEONY trial was not clinically relevant. While complete pathologic response most probably translates into long-term benefit for the patient, we still don’t know if it does for sure. Unfortunately, the PEONY trial was not powered enough to provide us with survival data after longer follow-up. Nevertheless, we have to wait for clear evidence of long-term survival benefit for breast cancer patients from all races in order to be able to expose our patients to all the complications related to the combined treatment evaluated in the PEONY trial.

As stated before, extrapolating toxicities from chemotherapy across ethnicities is difficult or even not possible (5) and emphasizing the need to validate safety of chemotherapeutic regimens in patients of different ethnicities.

The results of PEONY trial stay in line with result of the NEOSPHERE trial and constitute therefore a strong argument for combining pertuzumab with docetaxel in breast cancer patients also in Asian population. For a definitive argument in favor, we’ll have to wait to see clear survival benefit.

Acknowledgments

Funding: None.

Footnote

Provenance and Peer Review: This article was commissioned by the Editorial Office, Gland Surgery. The article did not undergo external peer review.

Conflicts of Interest: Both authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/gs.2020.03.26). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

References

1. Gianni L, Pienkowski T, Im YH, et al. Efficacy and safety of neoadjuvant pertuzumab and trastuzumab in women with locally advanced, inflammatory, or early HER2-positive breast cancer (NeoSphere): a randomised multicentre, open-label, phase 2 trial. Lancet Oncol 2012;13:25-32. [Crossref] [PubMed]
2. Chow LWC, Biganzoli L, Leo AD, et al. Toxicity profile differences of adjuvant docetaxel/cyclophosphamide (TC) between Asian and Caucasian breast cancer patients. Asia Pac J Clin Oncol 2017;13:372-8. [Crossref] [PubMed]
3. Szloch J, Marczyk E, Kołodziej-Rzepa M, et al. Impact of different type of cancer treatment on the effectiveness of breast reconstruction. Gland Surg 2016;5:444-9. [Crossref] [PubMed]
4. Shao Z, Pang D, Yang H, et al. Efficacy, Safety, and Tolerability of Pertuzumab, Trastuzumab, and Docetaxel for Patients With Early or Locally Advanced ERBB2-Positive Breast Cancer in Asia: The PEONY Phase 3 Randomized Clinical Trial. JAMA Oncol 2020;6:e193692. [PubMed]
5. Han HS, Reis IM, Zhao W, et al. Racial differences in acute toxicities of neoadjuvant or adjuvant chemotherapy in patients with early-stage breast cancer. Eur J Cancer 2011;47:2537-45. [Crossref] [PubMed]