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| LETTER TO EDITOR |
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| Year : 2022 | Volume
: 5
| Issue : 1 | Page : 183-184 |
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Authors' reply to Muddu and Boindala
Rakesh Sharma1, Ajay Gogia2
1 Department of Medical Oncology, All India Institute of Medical Sciences, New Delhi, India
2 Department of Laboratory Oncology, All India Institute of Medical Sciences, New Delhi, India
| Date of Submission | 01-Feb-2022 |
| Date of Decision | 26-Feb-2022 |
| Date of Acceptance | 01-Mar-2022 |
| Date of Web Publication | 31-Mar-2022 |
Correspondence Address:
Ajay Gogia
Department of Medical Oncology, IRCH, AIIMS New Delhi - 110 029
India
 Source of Support: None, Conflict of Interest: None
DOI: 10.4103/crst.crst_66_22
How to cite this article:
Sharma R, Gogia A. Authors' reply to Muddu and Boindala. Cancer Res Stat Treat 2022;5:183-4 |
We thank Muddu and Boindala[1] for their comments on our article titled, “Management of triple-negative breast cancer in the era of novel therapies: A narrative review.”[2]
We are aware of the heterogeneity of outcomes associated with the addition of immune checkpoint inhibitors (ICIs) to neoadjuvant chemotherapy (NACT) in triple-negative breast cancer (TNBC). Nevertheless, most of the trials have demonstrated increased pathological complete response rates (pCR) with the addition of ICI to NACT in TNBC. Attainment of pCR has become an established surrogate marker for assessing long-term survival in breast cancer, especially in TNBC and human epidermal growth factor receptor-2 (HER2)-positive breast cancer subtypes.[3],[4],[5] A meta-analysis by Huang et al.,[6] restricted to patients with TNBC, demonstrated a survival advantage with the achievement of pCR versus no pCR, with a 5-year recurrence-free survival (RFS) of 86% versus 50% and a 5-year overall survival (OS) of 92% versus 58%, respectively. The updated analysis of the KEYNOTE-522 trial demonstrated a 3-year event-free survival (EFS) benefit with the addition of pembrolizumab to chemotherapy; 84.5% vs. 76.8% 76.8%; Hazard Ratio, 0.63; 95% Confidence Interval, 0.48–0.82; P = 0.0003. However, the EFS benefit was driven mainly by patients not achieving pCR, and no OS benefit has been demonstrated.[7] A longer follow-up will delineate the survival benefit of the addition of pembrolizumab. The meta-analysis conducted by Conforti et al.,[8] which included all subtypes of breast cancer defined by hormone receptor and HER2/neu expression, should be interpreted with caution in the setting of TNBC.
As for the primary endpoint of the trial, pCR seems to be an appropriate surrogate for survival outcome. RFS and/or OS are the most desirable primary endpoints; however, a requirement of longer follow-up in early disease makes them redundant. TNBCs comprise various molecular subtypes defined by altered molecular pathways and potentially targetable biomarkers.[9] Currently, the management of early TNBC is not directed by molecular subtypes, but, if future trials are designed based on molecular subtypes, immune-enriched subtypes should be targeted with ICIs.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
| References | |  |
| 1. | Muddu VK, Boindala N. Immunotherapy for triple-negative breast cancer: Time to pause? Cancer Res Stat Treat 2022;5:182-3.  [Full text] |
| 2. | Sharma RK, Gogia A. Management of triple-negative breast cancer in the era of novel therapies: A narrative review. Cancer Res Stat Treat 2021;4:668-76. [Full text] |
| 3. | Cortazar P, Zhang L, Untch M, Mehta K, Costantino JP, Wolmark N, et al. Pathological complete response and long-term clinical benefit in breast cancer: The CTNeoBC pooled analysis. Lancet 2014;384:164-72. |
| 4. | Choudhary P, Gogia A, Deo SV, Sharma D, Mathur SR, Batra A, et al. Correlation of pathological complete response with outcomes in locally advanced breast cancer treated with neoadjuvant chemotherapy: An ambispective study. Cancer Res Stat Treat 2021;4:611-20. [Full text] |
| 5. | Badwe RA, Parmar V, Nair NS. Predicting pathological complete response post neoadjuvant chemotherapy and personalizing therapy in breast cancer. Cancer Res Stat Treat 2021;4:726-7. [Full text] |
| 6. | Huang M, O'Shaughnessy J, Zhao J, Haiderali A, Cortes J, Ramsey SD, et al. Association of pathologic complete response with long-term survival outcomes in triple-negative breast cancer: A meta-analysis. Cancer Res 2020;80:5427-34. |
| 7. | Schmid P, Cortes J, Dent R, Pusztai L, McArthur H, Kümmel S, et al. VP7-2021: KEYNOTE-522: Phase III study of neoadjuvant pembrolizumab+chemotherapy vs. placebo+chemotherapy, followed by adjuvant pembrolizumab vs. placebo for early-stage TNBC. Ann Oncol 2021;32:1198-200. |
| 8. | Conforti F, Pala L, Sala I, Oriecuia C, Pas T De, Specchia C, et al. Evaluation of pathological complete response as surrogate endpoint in neoadjuvant randomised clinical trials of early stage breast cancer: Systematic review and meta-analysis. BMJ 2021;375:e066381. |
| 9. | Marra A, Trapani D, Viale G, Criscitiello C, Curigliano G. Practical classification of triple-negative breast cancer: Intratumoral heterogeneity, mechanisms of drug resistance, and novel therapies. NPJ Breast Cancer 2020;6:1-16. |
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