Jame Abraham, MD, FACP on the PATINA Trial

Speaker 1: So PATINA trial is another really exciting trial which was presented at San Antonio SBCS 2024. So it's a randomized open label phase three trial to evaluate the efficacy and safety of Calbocycline plus anti HE2 treatment plus endocrine treatment versus anti HER2 therapy plus endocrine therapy after induction treatment for hormone receptor positive, HER2 positive metastatic breast cancer. About 15 to 20% of breast cancers over expressed HER2 and half of the HER2 positive tumors also co-express estrogen receptors. As we all know, the anti HER2 therapies have came a long way. And then THP, THP based upon the Cleopatra trial by Sandy Swain's group, is the gold standard in first line, HER2 positive metastatic breast cancer today. Of course this can be improved on that gold standard. So there is a number of rationale for blocking CDK four six in HER2 positive disease. The second one, CDK4/6 is essential for the initiation and maintenance of growth, AB two to one mammary carcinoma and persistence cycling D one CDK for activity drives resistant to HER2 pathway blockade. So potentially combining CDK4/6 and HER2 inhibition shows synergistic antitumor activity that is shown in preclinical models in HER2 positive breast cancer. Of course, Palbociclib is approved for metastatic ER positive breast cancer. So the study is hormone receptor positive, HER2 positive metastatic breast cancer. No prior treatment in metastatic setting. Six to eight cycles of treatment with Trastuzumab, plus or minus Pertuzumab and a Taxane or [inaudible 00:02:39]. Then the patient should have a complete response or a partial response after a six to eight cycles of chemotherapy. Then the patients are randomized. About 418 patients randomized one to one. The standard arm is Trastuzumab, Pertuzumab, plus endocrine treatment and the intervention is Palbociclib 125 milligrams PO daily, day one to 21. Our standard dosing of Palbociclib plus Trastuzumab plus Pertuzumab plus endocrine treatment. The standard maintenance regimen we use in Cleopatra, and then we are adding Palbociclib to that and the treatment is continued until progression of the disease or toxicity. The conclusion of the study really reinforced the strong scientific rationale for overcoming resistant to anti-HER2 therapy and endocrine treatment by adding CDK4/6 inhibition. Addition of Palbociclib to anti-HER2 plus endocrine treatment demonstrated a significant improvement in progression-free survival in patients with hormone receptor positive, HER2 positive advanced breast cancer in first-line metastatic setting. And the side effects were really manageable. So what do I do in clinic? I think this is a really interesting study. This is, and I'm giving almost more than a year of improvement in progression-free survival by addition of Palbociclib. So I think this is a potentially practice-changing study, but there are some caveats. One, at this point, of course, THP is the standard of treatment, but there are a number of trials which are looking at the role of other novel agents such as T-DXd in first-line setting, THP versus T-DXd that's being investigated. And then of course the role of other TKIs, that's being investigated in this setting, especially in the maintenance setting. So I think we need to see how this is going to play out when the results of some of the novel antibody drug conjugates come. But at this point, this is potentially a practice-changing study.