What are your top takeaways in Medical Oncology from SABCS 2024?

I would give the following studies the top 3 in terms of impact:

1. GS2-12:The PATINA study, that tested the use of palbociclib in patients who were on maintenance first-line therapy after induction therapy for metastatic HER2 and hormone receptor-positive breast cancer with taxane or vinorelbine plus trastuzumab with or without pertuzumab and after going on maintenance antibody and endocrine therapy, were randomized to palbociclib vs. placebo. There was a clear reduction in the primary endpoint of progression events with an extension of progression-free survival by 15 months. Median follow-up was 52.6 months and the hazard ratio for progression was 0.74. Treatment was well-tolerated, with the exception of grade 3 diarrhea seen in 11% of patie...

1. I was very impressed by the increased efficacy seen by adding palbociclib to endocrine therapy + H/P in the PATINA trial
   
   
2. I was excited to see the combination data of an oral SERD and a CDK4,6 inhibitor in the EMBER trial
   
   
3. I thought the post hoc analysis of TAILORx showing the additional benefit of anthracycline in patients with Oncotype scores >31 was provocative and something that we will need to discuss with our patients

1. PATINA Trial: The PATINA trial evaluated the addition of palbociclib, a CDK4/6 inhibitor, to standard HER2-targeted therapy and endocrine therapy in patients with ER+/HER2+ metastatic breast cancer. The study involved 518 patients who had undergone six cycles of initial treatment with taxane, trastuzumab, and pertuzumab (THP). Patients with disease control were randomized to continue with trastuzumab and pertuzumab (HP) plus endocrine therapy, with or without palbociclib. The PATINA trial offers a significant step forward in managing ER+/HER2+ metastatic breast cancer by integrating palbociclib into HER2-targeted and endocrine therapies. The PFS was significantly longer in the group of patients treated with palbociclib (median PFS 44 month...

1. The AFT-38 PATINA Trial for triple positive metastatic breast cancer. This was a phase III study of adding palbociclib to the first line treatment maintenance regimen. In this study, all triple positive patients (n=518) completed a standard six cycles of THP therapy and then there was a randomization between standard HP maintenance and palbociclib+HP maintenance. The patients randomized to the palbo+HP had a median PFS of 44 months compared to a PFS of 29 months in the HP alone arm. The OS is not yet mature. The overall response rate and the clinical benefit rate also strongly favored the palbo+HP arm. The safety profile was without any new safety signal beyond the expected profiles for palbociclib and HP. It should be noted that the PFS t...

1. GS3-03: Impact of Anthracyclines in High Genomic Risk Node-Negative HR+/HER2-Breast Cancer
   In patients with HR+/HER2-negative, node-negative breast cancer, a post hoc analysis of over 2,500 patients from the TAILORx trial showed benefit to the addition of anthracyclines to a taxane-based chemotherapy regimen in patients with a recurrence scores ≥31, but the benefit was limited to those patients with tumors ≥ 2cm in size. Moreover, the benefit of adding anthracyclines increased as the recurrence score increased over 31. This is interesting in that the ABC trials had previously demonstrated that there was poor correlation between the number of lymph nodes and the benefit of anthracyclines, indicating that nodal status might not be the best bi...

1. EMBER-3 – a new SERD that works in ESR1mt patients AND can be combined with CDK4/6i (and work in ESR1mt or wt), including after CDK4/6i.
2. PATINA – adding CDK4/6i to anti-HER2 and ET in MBC
3. COMET – potential for watchful waiting in low-risk DCIS

1. AFT-38 PATINA, Phase III study of Maintenance therapy with palbociclib plus endocrine therapy and trastuzumab+/-pertuzumab vs. endocrine therapy+ Trastuzumab+/-pertuzumab after 6- 8 cycles of induction chemotherapy for HR+ Her2 negative metastatic breast cancer:

Triple-positive metastatic breast cancer patients without progression after 6-8 cycles of induction taxane/vinorelbine + trastuzumab +/-pertuzumab were randomized to endocrine therapy +trastuzumab +/- pertuzumab maintenance therapy with or without palbociclib. About 97% received pertuzumab and ~90% aromatase inhibitors in both arms. The addition of palbociclib improved median progression free survival from 29.1 to 44.3 months (HR 0.74) at 52 months follow up. Overall survival is s...

1. ZEST trial showing the difficulty in using ctDNA to escalate therapy in curative setting. Need to work on sensitivity and testing schedules to optimize how we use these tests to improve cure rates while personalizing therapy.
   
   
2. PATINA is solid phase 3 data to enable us to add palbociclib in ER+HER2+ after the CLEOPATRA regimen.
   
   
3. EMBER data will hopefully lead to another SERD option in metastatic ER+ breast cancer.

1. Imlunestrant (EMBER-3 Trial)
Imlunestrant, a novel oral estrogen receptor (ER) degrader, showed marked improvements in progression-free survival among patients with ER-positive/HER2-negative advanced breast cancer, especially those harboring ESR1 mutations. Phase 3 findings from the EMBER-3 trial indicated a generally manageable safety profile, commonly featuring hot flashes and joint discomfort. When combined with abemaciclib (a CDK4/6 inhibitor), it delivered even greater benefits, suggesting strong synergistic potential. By targeting both wild-type and mutated ERs, Imlunestrant opens a promising new treatment avenue.

But the bottom line is: what will the FDA ultimately approve? Additionally, what can we learn from this trial’s design, a...

1. AFT-38 PATINA: A Randomized, Open Label, Phase III Trial to Evaluate the Efficacy and Safety of Palbociclib + Anti-HER2 Therapy + Endocrine Therapy vs. Anti-HER2 Therapy + Endocrine Therapy after Induction Treatment for Hormone Receptor-Positive (HR+)/HER-Positive Metastatic Breast Cancer: The study enrolled 518 patients with HR+ HER2+ MBC who completed 6-8 cycles of induction therapy with trastuzumab +/- pertuzumab and taxane/vinorelbine without disease progression in the first-line metastatic setting and randomized 1:1 for patients to receive either standard maintenance regimen of trastuzumab +/- pertuzumab + endocrine therapy (n=257) or also adding palbociclib to the maintenance regimen (n=261). The majority of patients received pertuzu...

The PATINA study was a randomized phase 3 study for patients with metastatic triple positive breast cancer. Participants received induction chemotherapy with HP as part of first line treatment of triple positive breast cancer and were randomized to palbociclib with anti-HER2 therapy and endocrine therapy versus anti-HER2 therapy and endocrine therapy. Median progression-free survival in the palbociclib group was higher, 44.3 months, than the control arm, 29.1 months. There were some increased toxicities with the palbociclib arm, such as grade 3 neutropenia, but the authors noted that the side effects appeared to be manageable. These encouraging results may give patients with metastatic triple positive breast cancer new options.

The addition of palbociclib to maintenance HER2-directed and endocrine therapy significantly improves PFS in patients with hormone receptor-positive, HER2-positive metastatic breast cancer