DESTINY-Breast09 is Trending, What About PATINA?

With yet another exciting Press Release this week, AstraZeneca announced that the DESTINY-Breast09 trial was positive

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Key Opinion Leaders, (KOLs), in breast cancer were buzzing about the Press Release Announcement on X:

Key Opinion Leader	Tweet	Source
Dr. Elisa Agostinetto	As expected, DB-09 showed significant improvement in PFS with T-DXd in 1st line in combination with pertuzumab, thus likely representing a practice-changing study for HER2+ #breastcancer	Link
Dr. Stephanie Graff	This is unsurprising, given the success of T-DXd in HER2+ BC, but the question will now be "for how long" and possible if/when de-escalation strategies, knowing that many patients on THP were able to be on HP or H for a long time with near normal QoL.	Link
Dr. Paolo Tarantino	ADCs are rapidly moving to earlier line treatment for breast cancer. Will likely reach the (neo)adjuvant setting soon.	Link
Dr. Komal Jhaveri	Another treatment option for our patients with HER2 positive MBC in the 1L setting. TDXD + P was better than THP in DB-09. Awaiting details on magnitude of benefit and safety at upcoming meeting.	Link
Dr. Kristina Jankovic	DESTINY-Breast09: Enhertu + pertuzumab shows superior PFS vs THP in 1L HER2+ mBC — first regimen in over a decade to outperform SoC	Link

This is a highly anticipated trial in Breast Cancer and KOLs have been buzzing about the results of this trial since the #SABCS24 discussion of PATINA. In the Tweet below, Dr. Ambika of Cancer Care Specialists of Reno, NV, predicted that the DESTINY-Breast09 data would "complicate the picture."

What is DESTINY-Breast09?

Dr. Taro Yamanaka  of the National Cancer Center Hospital in Tokyo, Japan.reviews the trial results below:

Amongst the excitement of DESTINY-Breast09, Dr. Sammons from Dana-Farber reminded her colleagues to think about the ER + "Patina patients".

What is the PATINA Trial?

The PATINA trial is a randomized phase 3 clinical study focused on evaluating the efficacy of adding a CDK4/6 inhibitor, specifically palbociclib, to standard treatment regimens for patients with hormone receptor-positive, HER2-positive metastatic breast cancer. The study goal was to determine whether this addition can improve progression-free survival for these patients. Patients were randomized after induction chemotherapy based combination regimen(Taxane, Herceptin, Pertuzumab).

Results: Source (Dr. Otto Metzger)

1. Progression-Free Survival (PFS): The addition of a CDK4/6 inhibitor, palbociclib, significantly improved progression-free survival. The median PFS for patients in the control arm was 29.1 months, while it increased to 44.3 months for those treated with the CDK4/6 inhibitor, palbociclib.

2. Hazard Ratio: This translates to a hazard ratio of 0.74, meaning there was a 26% reduction in the risk of a progression-free survival event for patients treated with the CDK4/6 inhibitor.

3. Overall Survival Data are Immature

Below is an overview of the PATINA study from Dr. Wolfgang Janni:

Key Aspects of the PATINA Trial:

1. Encouragement of CDK4/6 Inhibitor activity in this patient setting: At 08:11 in the OncoAlert SABCS24 Video discussion, Dr. Peter Fasching of Universitätsklinikum Erlangen remarks, "It's already known for a very long time that there's a very good efficacy of CDK4/6 inhibitors in patients with HER2 positive disease and having a chemo-free option that is very efficacious and the medium PFS time is getting over 40 months. Ah, that's very impressive."

2. Practice-changing Potential: At 11:48, Dr. Nadia Harbeck of Ludwig-Maximilian University states, "I think we heard one study, PATINA which is going to be practice changing, I think the data were so fascinating.
3. Is Induction Chemo Necessary based on PATINA Efficacy Reults? KOLs around the globe were so impressed with the PATINA data that they wondered aloud if all patients should receive the induction chemo regimen prior to the experimental arm of PATINA. ​Dr. Diana Lüftner of Immanuel Klinik Märkische Schweiz, noted at 9:50, "My first question is, can we skip chemotherapy? Of course, this is a selected, patient population, the primary progressive patients were taken out. But is the efficacy high enough that you would really skip the introduction with the chemotherapy?" In another SABCS24 Summary, PATINA Researcher Dr. Otto Metzger shared a similar viewpoint, "And there are many patients who have indolent disease and they can go straight into a regimen that has minimal toxicity, no chemotherapy-related toxicity. So my gut feeling is that physicians are going to be able to find out who these patients are and we will have more confidence with the regimen that's going to be given to these patients given the results that we saw today with PATINA"
   
4. "It Really is Quite Stunning": Dr. Lisa Carey, UNC Lineberger Comprehensive Cancer Center reviews the benefits of palbociclib seen in PATINA from a mechanism of action perspective: "It really is quite stunning. And just remember, through this simple machinery of a CDK4/6 inhibitor which we're all very familiar with and we use all the time, you're now circumventing endocrine therapy resistance because hormone receptor positive breast cancer, and you're circumventing HER2 resistance because they're all HER2 positive..."
   
   

5. Consistent Adverse Event Profile: Dr. Metzger, Dana-Farber, noted that the PATINA regimen saw an adverse event profile consistent with prior studies of palbociclib with an increase in diarrhea. He mentioned that researchers are attempting to discern if the higher rare of diarrhea was due to the induction chemotherapy.

What's Complicated about DESTINY-Breast09 and PATINA?

Dr. Erika Hamilton, Sarah Cannon Research Institute, and Dr. Sarah Sammons discussed a potential maintenance strategy during the #SABCS24 tweet discussions: