Expert Point of View: Stephen K.L. Chia, MD


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It’s reasonable to consider nab-paclitaxel over solvent-based paclitaxel, to eliminate steroids and allergic reactions, but … that is offset by increased cost.
— Stephen K.L. Chia, MD

Stephen K.L. Chia, MD, of the British Columbia Cancer Agency, Vancouver, discussed two of these neoadjuvant breast cancer studies at the ASCO Annual Meeting.

In the current landscape for neoadjuvant therapy in HER2-positive disease, said Dr. Chia, the NeoSphere, ­TRYPHAENA, KRISTINE, and I-SPY 2 trials all support the use of neoadjuvant pertuzumab (Perjeta) given concurrently with a taxane.

Similar to the pathologic complete response rates of 44% and 56% in KRISTINE, this endpoint was 39% with trastuzumab (Herceptin)/docetaxel plus pertuzumab in NeoSphere,1 64% with docetaxel/carboplatin/trastuzumab plus pertuzumab in TRYPHAENA,2 and 52% with ado-trastuzumab emtansine (Kadcyla) plus pertuzumab in I-SPY 2.3

On the other hand, no evidence yet supports the adjuvant use of pertuzumab or ado-trastuzumab emtansine, he said. The results of the APHINITY trial, which is evaluating trastuzumab plus pertuzumab in the adjuvant setting, “are eagerly awaited,” he added.

Corroboration and Discrepancies

According to Dr. Chia, while KRISTINE supports the neoadjuvant use of pertuzumab, it does not support ado-trastuzumab emtansine in this setting, with or without pertuzumab. “It’s clear there is a more favorable toxicity profile,” he acknowledged, “but it’s offset by increased financial cost.”

The KAITLIN trial is comparing ado-trastuzumab emtansine/pertuzumab to trastuzumab/pertuzumab plus a taxane in the adjuvant setting. “Unfortunately, I am not optimistic that we will see a superiority signal in KAITLIN, although I acknowledge that the longer duration of ado-trastuzumab emtansine/pertuzu­mab in KAITLIN vs KRISTINE and the adjuvant delivery of anthracycline may be significant factors” he commented.

Discussing the ETNA study, Dr. Chia noted that the results differ from those seen in GeparSepto.4 With nab-paclitaxel, pathologic complete response rates were 22.5% in ETNA but 38% in GeparSepto, although odds ratios were similar for the two trials. The triple-negative subtype in GeparSepto had the best response to nab-paclitaxel.

Potential reasons for this discrepancy pertain to heterogeneity in trial populations and in pathology assessment for pathologic complete response, not to differences in dose and schedule of the control arms, he said.

“It appears there is a modest improvement, at best, with nab-paclitaxel,” he concluded. “You are able to deliver a higher dose, but this leads to more neuropathy and neutropenia. It’s reasonable to consider nab-paclitaxel over solvent-based paclitaxel, to eliminate steroids and allergic reactions, but again, that is offset by increased cost.”

Looking Ahead

“Going forward, we need to find a predictive biomarker beyond the subtype of triple-negative breast cancer,” he added.

Dr. Chia said the studies also yield “lessons for future trials.” One is to strive for standard chemotherapy backbones given preoperatively, and another is to stop enrolling patients in adjuvant trials without a positive signal from the neoadjuvant setting. The focus on adjuvant trials, he added, should be on patients with residual disease after neoadjuvant treatment.

“We should consider that, in some subtypes (eg, HER2-positive/hormone receptor–negative subtype), we can actually replace adjuvant trials,” he suggested. ■

Disclosure: Dr. Chia has received honoraria from Genomic Health, Novartis, and Roche; research funding from Novartis and Roche; and reimbursement for travel, accommodations, and expenses from Celgene and Roche. He also has had a consulting or advisory role with Novartis and Roche and has served on speakers bureaus for Genomic Health and Novartis.

References

1. Gianni L, Pienkowski T, Im Y-H, et al: Efficacy and safety of neoadjuvant pertuzumab and trastuzumab in women with locally advanced, inflammatory, or early HER2-positive breast cancer (NeoSphere). Lancet Oncol 13:25-32, 2012.

2. Schneeweiss A, Chia S, Hickish T, et al: Pertuzumab plus trastuzumab in combination with standard neoadjuvant anthracycline-containing and anthracycline-free chemotherapy regimens in patients with HER2-positive early breast cancer. Ann Oncol 24:2278-2284, 2013.

3. DeMichele AM, Moulder S, Buxton M, et al: Efficacy of T-DM1 + pertuzumab over standard therapy for HER2+ breast cancer: Results from the neoadjuvant I-SPY 2 trial. 2016 AACR Annual Meeting. Abstract CT042. Presented April 18, 2016.

4. Untch M, Jackisch C, Schneeweiß A, et al: A randomized phase III trial comparing neoadjuvant chemotherapy with weekly nanoparticle-based paclitaxel with
solvent-based paclitaxel followed by anthracyline/cyclophosphamide for patients with early breast cancer (GeparSepto); GBG 69. 2014 San Antonio Breast Cancer Symposium. Abstract S2-07. Presented December 10, 2014.


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