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Results from monarchE (abemaciclib + ET) confirm the benefit of abemaciclib in in high risk, HR+ BC

Although FDA ODAC voted unanimously to defer a regulatory decision on pembrolizumab for neoadjuvant treatment followed by adjuvant treatment of high-risk early-stage TNBC until further data are available from KEYNOTE-522, physicians remain hopeful that the study will eventually be successful

Addition of ipatasertib to chemotherepy did not show benefit in a Phase III trial (IPAtunity130) leaving the future of AKT inhibitors in mTNBC unclear

FDA approved multiple agents in 2020 including pembrolizumab in combination with chemotherapy for PD-L1+ (CPS ≥10) mTNBC, sacituzumab govitecan for patients with mTNBC who received at least two prior therapies, and tucatinib in combination with trastuzumab and capecitabine, for mHER2+ BC who have received one or more prior anti-HER2-based regimens

Topic 1: TNBC


Topic 1: TNBC

Additional Chemotherapy Options with checkpoint inhibitors in TNBC: Analysis from the PIII KEYNOTE-355 study showed an improved PFS benefit of pembrolizumab + chemo (pac, nab-pac, or gem/carbo) vs placebo + chemo in PD-L1+ patients with CPS>10. The study results supported the FDA approval of pembrolizumab + chemo in PD-L1+ 1L mTNBC and provide physicians with additional chemotherapy options to treat patients, including platinum chemotherapy.

“It’s exciting to have these chemotherapy options available for mTNBC patients. Of course, the big advantage is that now you can use a taxane or a platinum with IO.” – US KOL

The Future of AKTi in TNBC is unclear: Conflicting data from the PIII IPATunity130 (ipatasertib + chemo) and PII PAKT (capivasertib + chemo) trials in mTNBC has provided more questions than answers on the role of AKTi in TNBC. Phase III IPATunity130 failed to show a benefit in PIK3CA/AKT/PTEN altered patients, whereas the Phase II PAKT trial did show a benefit using an all-comers approach. Ongoing Phase III CAPItello-290 trial is evaluating capivasertib + chemo in the ITT population. However, it is still unclear how this unselected population will lead to improved outcomes in 1L TNBC.

“I think it’s important to remember that TNBC is a very heterogeneous disease. We know AKTi have an effect on the immune system, but maybe even if we don’t see an effect with PFS, we will see an effect with OS.” – US KOL

ODAC Votes to Wait on Pembrolizumab Approval in High-Risk early TNBC: FDA Oncology Drug Advisory Committee (ODAC) voted unanimously to defer a regulatory decision on pembrolizumab for neoadjuvant treatment followed by adjuvant treatment of high-risk early-stage TNBC until further data are available from KEYNOTE-522. The setback highlights tough regulatory scrutiny ahead for all IO agents across early-stage solid tumors, and limitations of pCR as an endpoint to support neoadjuvant approvals. Merck is expected to have its next interim readout from KEYNOTE-522 in the third quarter 2021, and physicians remain positive that the study will eventually be successful.

Olaparib adjuvant therapy crossed the superiority bar in HER2-negative BRCAm: Following recommendations from IDMC, OlympiA (Phase III trial of olaparib in the adjuvant treatment of BRCAm high-risk HER2-negative early breast cancer) will be analyzed and reported early. Based on the planned interim analysis, the IDMC concluded that “the trial crossed the superiority boundary for its primary endpoint of iDFS and demonstrated a sustainable, clinically relevant treatment effect”.

ASCENT trial shows sacitizumab provides survival benefit regardless of TROP2 expression: Biomarker evaluation of the PIII ASCENT trial confirms the benefit of sacituzumab govitecan regardless of TROP2 expression levels. Although increased efficacy was observed in tumors with higher TROP2 expression, TROP2 is not considered a predictive biomarker since the benefit was observed across the various subgroups.

Topic 2: HR+ BC

monarchE and Penelope-B studies highlight potential differences between CDK4/6i in the AT setting: The updated results from monarchE (abemaciclib + ET) in high risk, HR+ BC confirm the benefit of abemaciclib in this high risk patient population, showing improved iDFS and DRFS outcomes. Conversely, longer follow-up data from the Penelope-B trial showed that palbociclib failed to improve outcomes in the adjuvant setting in a similar patient population. This discrepancy between the two CDK4/6i trials highlights the importance of longer follow-up in this setting and the need to better understand how CDK4/6i are acting at this stage. Results from the NATALEE trial (ribociclib + ET) are expected to shed further light into this question.

“They have different risk populations, different discontinuation rates, and there are differences in the CDK4/6i, but ultimately we have to think about whether we are just delaying metastatic presentation or if some patients will be cured.” – US KOL

· RxPONDER shows that not all HR+ eBC pts need chemotherapy. RxPONDER found that postmenopausal women with HR-positive, HER2-negative BC with 1-3 positive nodes and a 21-gene recurrence score (RS) of ≤ 25 (Oncotype DX) derived no further benefit from chemotherapy added to endocrine therapy and can safely avoid adjuvant treatment with it. On the other hand, premenopausal women with the same characteristics experienced a 45% relative risk reduction in invasive disease–free survival events with the addition of chemotherapy, showing that while some patients do benefit from chemotherapy, not all patients need to be treated with it.

“Of any of the data presented at SABCS, this was without a doubt the most clinically significant and practice changing because it showed us not all patients need chemo.” - US KOL

· Oral Taxanes in mBC: Results from the CONTESSA trial showed that the orally administered taxane, tesetaxel, was able to improve PFS in HR+ mBC pts who have previously received a taxane vs reduced-dose capecitabine. Similarly, oral paclitaxel was shown to yield superior results when compared to intravenous paclitaxel in mBC. These oral taxanes regimens will provide new therapeutic options for patients and are an important advance in the management of patients with mBC.

Topic 3: HER2+ BC

· A new ADC in heavily pretreated HER2+ mBC. Updated results from the positive DESTINY-Breast01 Phase II trial showed that Enhertu (trastuzumab deruxtecan) continues to demonstrate impressive efficacy and durable responses in patients with HER2-positive metastatic breast cancer following two or more prior HER2-based regimens and these data were used to support the approval of Enhertu in 3L+ HER2+ mBC. These data now provide pts with an option where no SOC currently exists, in pts who have developed resistance to HER2-directed therapies such as Herceptin, Perjeta, and Kadcyla.

“The durability is what’s really great—to see a response that lasts 20 months or more – I think that’s exciting, especially in these heavily pre-treated patients.” – US KOL

· Tucatinib – New option for mHER2+ patients, including patients with brain metastases. The HER2CLIMB data at SABCS showed that the small molecule HER2 inhibitor, tucatinib, when added to trastuzumab/capecitabine was able to reduce the risk of death reduced the risk of disease progression in patients with heavily pretreated metastatic HER2-positive breast cancer, including those with untreated or previously treated brain metastasis. This is the first completed randomized trial to include patients with brain metastases and provides this combination with the potential to become the SOC in this patient population both with and without brain metastases.

“People in certain parts of the world don’t have access to these treatments, but the hope is that by sharing these data, we help you manage patients and translate the information to your own clinical practices and help you look forward into the future.

Axiom hosted a Town Hall Event on SABCS on 12/18/2020, where we conversed with leading opinion leaders who shared their insights and commentary on some major Breast Cancer topics that are detailed above.

Video Recording from the SABCS 2020 Event is Available Here

For Details on Axiom’s Capabilities in Breast Cancer, Contact:

Hafiz Sikder –

Mahim Misra –

A year In Review- Breast Cancer_Axiom
Download PDF • 1.76MB

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