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2024 SABCS Highlights

CME

CCO Independent Conference Highlights of the 2024 San Antonio Breast Cancer Symposium

Physicians: Maximum of 1.50 AMA PRA Category 1 Credits™

Released: March 04, 2025

Expiration: September 03, 2025

Heather McArthur
Heather McArthur, MD, MPH, FASCO
Joyce O'Shaughnessy
Joyce O'Shaughnessy, MD
CME/CE Information

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neoHIP: Phase II Trial of Neoadjuvant Pembrolizumab Plus HER2-Targeted Therapy for HER2-Positive EBC

Heather McArthur, MD, MPH:
Immune checkpoint inhibition was shown to be synergistic with HER2-directed therapy in preclinical models,29-31 and pembrolizumab-mediated immune checkpoint inhibition with addition of HER2-directed therapy with trastuzumab was safe and demonstrated modest activity in trastuzumab-resistant, HER2-positive mBC.32 

At SABCS 2024, we presented data from the phase II neoHIP study evaluating neoadjuvant HER2-targeted therapy with or without immune checkpoint inhibition with pembrolizumab in patients with previously untreated, stage II/III, HER2-positive EBC with tumor size >2 cm and/or lymph node–positive status. Patients were randomized to receive docetaxel, trastuzumab, and pertuzumab (THP, arm A), or THP with pembrolizumab (arm B), or docetaxel and trastuzumab (TH) with pembrolizumab (arm C).33 Each treatment was administered for 4 cycles prior to surgery and patients (N = 138) were stratified by nodal status and HR status. The primary endpoint was pCR.

The idea was that if we administered these strategies early in the course of disease, namely in the neoadjuvant setting, that we may be able to:

  • Mitigate the need for polychemotherapy
  • Overcome the need for dual HER2-directed therapy with pertuzumab
  • Improve pCRs
  • Further confer lifelong tumor-specific immunity and better cure rates

Of note, enrollment to arm C was terminated after 22 patients were enrolled and underwent surgery because of a prespecified interim efficacy analysis. Also, additional chemotherapy was permitted before and after surgery if residual disease was biopsy proven after the intervention.

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neoHIP: Baseline Characteristics

Heather McArthur, MD, MPH:
The median age of patients enrolled in the study was approximately 52 years, and >50% of patients were White or non-Hispanic.

Most patients had T1 or T2 tumors (≥82%) and node-negative disease (≥60%). Most patients had HR-positive disease (≥62%). Thus, the arms were relatively well balanced.

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neoHIP: pCR (Primary Endpoint)

Heather McArthur, MD, MPH:
Looking at the primary endpoint of pCR, we see that the addition of pembrolizumab to THP improved pCR rates by 18.9% (from 48.3% to 67.2%), and pCR in arm C was only 25%. Moreover, improvement in pCR rates with the addition of pembrolizumab was observed regardless of the definition of pCR that was adopted (ypT0/TisypN0, ypT0ypN0, or ypT0/Tis).

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neoHIP: Safety Summary

Heather McArthur, MD, MPH:
Overall, the AEs were consistent with the known toxicity profile of THP, and the addition of pembrolizumab did not seem to significantly increase the AEs when compared with THP alone.

Immune-related AEs were more common in arm B (THP plus pembrolizumab) vs arm A (THP alone), including any-grade immune-related AEs (18.9% vs 6.8%, respectively); rash (15.9% vs 0%, respectively); alanine aminotransferase elevation (5.2% vs 0%, respectively); hypothyroidism (3.5% vs 0%, respectively); and pneumonitis (1.7% vs 0%, respectively).

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neoHIP: Takeaways

Heather McArthur, MD, MPH:
In my view, the addition of pembrolizumab to THP was safe and improved pCR rates, although it did not mitigate the need for dual HER2 blockade.

To our knowledge, this is the first study to demonstrate a clinically meaningful benefit with this combination in the curative-intent setting, particularly in the absence of an anthracycline-based regimen. Early administration of this combination may eliminate the need for polychemotherapy.

Additional analyses are ongoing, including for the longer-term impact of this combination therapy on EFS. We are excited about this combination, and the potential to create synergy with the combination of pembrolizumab and a HER2-directed agent with the intent to forgo chemotherapy that is much more toxic.

PATINA: Addition of Palbociclib to Anti-HER2 Therapy Plus ET vs Anti-HER2 Therapy Plus ET in HR-Positive/HER2-Positive mBC

Joyce O’Shaughnessy, MD:
Another important study presented at SABCS 2024 is the randomized, open-label phase III PATINA trial, which is evaluating the efficacy and safety of combining palbociclib with anti-HER2 therapy plus ET vs anti-HER2 therapy plus ET alone after induction treatment in patients with HR-positive/HER2-positive mBC (N = 518).34

In this study, patients who had a complete response (CR), PR, or stable disease after completion of 6-8 cycles of induction chemotherapy plus trastuzumab and pertuzumab or trastuzumab were randomized to receive either palbociclib 125 mg QD on Days 1 and 21 plus trastuzumab, with or without pertuzumab, plus ET; or trastuzumab, with or without pertuzumab, plus ET, without palbociclib. The primary endpoint of the study was PFS by investigator assessment and the secondary endpoint was OS.

PATINA: Baseline Characteristics

Joyce O’Shaughnessy, MD:
The median age of the patients enrolled was 53 years. The number of cycles of previous induction treatment was 6 for both arms. Overall, 97% of patients were treated with dual HER2 blockade. The most common type of ET used was an AI (~90%), followed by fulvestrant (~10%), and the most common response to induction therapy was CR/PR, which occurred in approximately 70% of patients.

PATINA: PFS (Primary Endpoint) and OS

Joyce O’Shaughnessy, MD:
The PATINA study met its primary endpoint of improving PFS. At a median follow-up of 52.6 months, the mPFS by investigator assessment was 44.3 months vs 29.1 months (hazard ratio: 0.74; 1-sided P = .0074) in favor of the combination of palbociclib with anti-HER2 therapy plus ET vs anti-HER2 therapy plus ET without palbociclib. We also see an early separation of the Kaplan-Meier curves (at ~3.5 months) that continued over time, with an absolute improvement in PFS rate at 5 years of approximately 10% (42.3% with palbociclib vs 33.4% without). All patient subgroups analyzed showed a benefit in PFS, as well as the confirmed ORR and CBR rates, with the addition of palbociclib.

The PATINA OS data were immature at this analysis. The median OS was not reached vs 77.0 months (hazard ratio: 0.86; 95% CI: 0.60-1.24), in favor of the combination of palbociclib with anti-HER2 therapy plus ET vs anti-HER2 therapy plus ET alone, and the 5-year OS rate was 74.3% vs 69.8%.

PATINA: Safety Summary

Joyce O’Shaughnessy, MD:
In the treatment arm that included palbociclib, the most common grade 2/3 AEs occurring in ≥10% of patients were neutropenia, fatigue, diarrhea, and stomatitis. These data are consistent with the toxicity profile for palbociclib.

The incidence of grade 4 AEs was similar in the 2 study arms. In the arm containing palbociclib, 7.5% of patients discontinued treatment because of AEs. No grade 5 events were reported in either arm of the study.

PATINA: Takeaways

Joyce O’Shaughnessy, MD:
The addition of palbociclib to the SoC CLEOPATRA regimen with ET significantly improved PFS in patients with HR-positive/HER2-positive ABC/mBC. The addition of palbociclib to anti-HER2 therapy with ET yielded a significant improvement in mPFS in this setting. OS data were immature at the time of this analysis. For me, pending FDA approval, the PATINA regimen should be considered a new SoC. So, very exciting data were presented at SABCS 2024.  

Which of the following findings was reported from the randomized, open-label phase III PATINA study evaluating the efficacy and safety of palbociclib combined with SoC anti-HER2 therapy plus ET vs anti-HER2 therapy plus ET alone after induction treatment in patients with HR-positive/HER2-positive mBC?

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