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Priya Rastogi, MD, Senior Medical Assistant Director at NSABP Medical Affairs, Associate Professor of Medicine at the University of Pittsburgh, provided clarification on this topic during a presentation she gave at the University of Pittsburgh. Opportunity of 2018 OncLive® Summit on the State of Science ™ on Breast Cancer. At the summit, she reviewed the data from each trial to explain why patients could benefit from de-escalating treatments.
The NSABP B-52 trial studied the regimen of docetaxel, trastuzumab (Herceptin) and pertuzumab (Perjeta), alone or in combination with endocrine therapy in patients with HER2 breast cancer positive hormone receptor positive. These patients then underwent surgery, with the main criterion being a complete pathological response (pCR).
"With blocked therapy with HER2-targeted therapy, you can see an escape mechanism via HER1 or EGFR." One of the arguments, when we were thinking of NSABP B-52, was that if you add estrogen deprivation, you may be able to completely block HER and emergencies, "said Rastogi.
The results presented at the 2016 Breast Cancer Symposium in San Antonio showed a numerical improvement in pCR for breast and lymph nodes, from 40.9% to 46.1% with the addition of deprivation. estrogen.1 There was also an increase in breast pCR, with an increase of 44.2% to 47.4% with the addition of estrogen deprivation. These results were significant numerically but not statistically, said Rastogi.
The conclusion of this study was that addition of estrogen deficiencies to neoadjuvant chemotherapy was not antagonistic and did not increase toxicity.
"Given the toxicity of standard chemotherapy observed in this trial, the findings of NSABP B-52 have advocated a tailor-made de-escalation approach, in which toxic treatments are replaced by less toxic treatments without compromising results, "explained Rastogi.
At the ASCO Annual Meeting in 2018, the results of the PERSEPHONE trial were presented. In this study, investigators evaluated the duration of trastuzumab in the treatment of patients with early-stage HER2-positive breast cancer. Patients in this study were randomized to receive either adjuvant trastuzumab for 6 months or standard 12-month treatment.
At the 5-year follow-up, the 4-year disease-free survival rate was 89.4% for 6-month treatment, compared to 89.8% for 12-month treatment, meeting the criteria for non-inferiority (HR, 1.07 90% CI, 0.93-1.24; P = .01).2 The sample size was 4088 patients and the investigators had estimated DFS at about 80%, said Rastogi.
Data on quality of life, patient-reported outcomes, and health outcomes are still expected, but a reduction in cardiac and other toxicities was observed with 6-month versus 12-week treatment. months, as well as lower costs for both patients. and health systems.
In addition, a predefined subgroup analysis showed that patients who had a negative estrogen receptor, received taxane-based chemotherapy or were undergoing concomitant chemotherapy with trastuzumab with a higher benefit with treatment of 12 month. Rastogi added that there was also only a small difference in overall survival (OS).
Another essay from the APT study that changed the practice, said Rastogi. Retrospective data suggest that patients with small HER2-positive breast cancer present a more than minimal risk of recurrence of the disease. Rastogi added that the majority of pivotal trials with adjuvant, including NSABP B-52, excluded these patients. Therefore, APT has been designed to treat the treatment of this population.
The results presented at the ASCO's 2017 annual meeting showed that after a 7-year follow-up, the trastuzumab / paclitaxel adjuvant combination is associated with fewer recurrences and 4 distant recurrences in patients with HER2-positive breast cancer with negative lymph nodes.3 The 7-year DFS rate was 93.3% and the 7-year interval without recurrence – including invasive locoregional diseases, distant recurrences, and deaths from breast cancer – was 97.5%. .
The investigators concluded that trastuzumab / paclitaxel adjuvant should be the standard treatment for patients with stage I HER2-positive breast cancer who have received chemotherapy and trastuzumab.
"With long-term follow-up, paclitaxel and trastuzumab adjuvants are associated with excellent results, suggesting that it remains a standard treatment regimen for the majority of patients with breast cancer. stage I HER2-positive, "said Rastogi. "Work is underway to better characterize the intrinsic subtypes, and formal analyzes will be conducted to see how the distribution compares to the larger HER2-positive tumors of other data sets."
The current ATEMPT trial (NCT01853748) builds on what has been demonstrated in the APT trial, Rastogi added. This trial compares ado-trastuzumab emtansine (T-DM1; Kadcyla) with paclitaxel and trastuzumab. This phase II trial is underway, but recruitment is complete.
References
- Rimawi MF, Cecchini RS, Rastogi P, et al. Phase III trial of pCR in HR +, HER2-positive breast cancer patients treated with neoadjuvant docetaxel, carboplatin, trastuzumab and pertuzumab (TCHP) +/- estrogen deficiency: NRG Oncology / NSABP B-52. In: Proceedings of the 2016 Breast Cancer Symposium in San Antonio; December 6-10, 2016; San Antonio, Texas. Abstract S3-06. doi: 10.1158 / 1538-7445.SABCS16-S3-06.
- Earl HM, L Hiller, Vallier A-L et al. PERSEPHONE: Adjuvant trastuzumab administered for 6 months versus 12 months in patients with early (+) HER2-positive breast cancer (+): randomized phase 3 non-inferiority trial with definitive disease-free survival at 4 years (year) DFS ) results. J Clin Oncol. 2017 36 (suppl., 506).
- Tolaney SM, Barry WT, Guo H et al. Seven-year follow-up (year) of paclitaxel (T) and trastuzumab (H) adjuvants (APT trial) for HER2-positive breast cancer (BC) with negative lymph nodes. J Clin Oncol. 2017 35 (addition 15): 511. doi: 10.1200 / JCO.2017.35.15_suppl.511.
Originally published on OncLive® as "Addressing the de-escalation of HER2 + breast cancer treatment"
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