Takeaways from SABCS, Part IV

If you've stuck with me through all of my takeaways from the San Antonio Breast Cancer Symposium (SABCS), then your brain is probably spinning! Don't worry, that's normal. I had that feeling at the end of all five (5) days there! This last installment is about some of the key trials that reported some results in San Antonio and is good to keep an eye on for the future.

Taxol (paclitaxel) updates

Oral Taxol (paclitaxel): According to a phase 3 clinical trial of metastatic breast cancer (MBC) patients that compared an oral version of the chemotherapy drug paclitaxel (Taxol) with the current FDA-approved intravenous (IV) form, the oral version elicited a better response and increased survival. Not only was overall survival increased in the oral version, but the incidence of neuropathy was also 17% in the oral group compared with 57% in the IV group, and was less severe. Conversely, neutropenia (low white blood count), infection, and gastrointestinal side effects were higher in the oral group, although these symptoms were generally low-grade.

CDK4/6 inhibitor updates

As many of you are probably already aware, the combination of a CDK4/6 inhibitor with endocrine therapy is the current standard first-line treatment for pre-, peri-, and postmenopausal patients (and men) with hormone receptor-positive, HER2 negative MBC. Both Verzenio and Kisqali show evidence of being effective against visceral disease and being able to penetrate the blood-brain barrier (BBB). Verzenio also appears to be a particularly effective therapy for harder-to-treat hormone receptor-positive patients with progesterone negative and/or high-grade MBC. However, in 2019, the FDA issued a warning that Ibrance, Kisqali, and Verzenio may cause rare but severe inflammation of the lungs, although the overall benefit is still considered greater than the risks.

Researchers have also identified the following biomarkers that may be indicative of resistance to CDK4/6 inhibitors:

De novo (initial) resistance

  • Rb1 loss
  • FAT1 loss via the hippo pathway o CCNE1 overexpression
  • FGFR1 amplification

Acquired Resistance

  • Rb1 loss
  • ERBB2 (HER2) mutation
  • PTEN loss of function mutations o AKT amplification
  • AURKA amplification

TRINITI-1 study

TRINITI-1 Study: Kisqali (Ribociclib), Afinitor (Everolimus), and Aromasin (Exemestane) after Prior CDK4/6 Progression – The Phase 1/2 TRINITI-1 trial evaluated triplet therapy with Kisqali, Afinitor, and Aromasin among 95 men and postmenopausal women with advanced hormone receptor-positive, HER2-negative breast cancer who received previous CDK 4/6 inhibitor therapy and up to three lines of prior therapy. The clinical benefit rate at 6 months was 41.1% (which was four times the minimum threshold for the study), the disease control rate was 61.1%, and the overall response rate was 8.4%. The median progression-free survival was 5.7 months.

FAKTION trial results

FAKTION Trial Results: Capivasertib (AZD5363) + Faslodex (Fulvestrant) vs. Faslodex Alone for Hormone Receptor-Positive, HER2 Negative Pre-Treated Patients – This Phase 2 study compared the results of administering Capivasertib + Faslodex, vs. Faslodex alone in 140 hormone receptor-positive, HER2 negative postmenopausal women who had relapsed on prior endocrine therapy. Capivasertib is a potent and selective inhibitor of AKT, which is a key node in the PI3K/AKT/mTOR signaling network. Patients were allowed a maximum of 1 line of prior chemotherapy and up to 3 lines of endocrine therapy for MBC. The median progression-free survival among patients receiving the combination was 10.3 months compared with 4.8 months for patients solely receiving Faslodex, and the median overall survival was 26.0 months versus 20.0 months respectively.

SAFIR02-IMMUNO trial results

SAFIR02-IMMUNO Trial Results: Imfinzi (Durvalumab) vs. Chemotherapy in Pre-Treated Patients – This Phase 2 trial enrolled HER2 negative locally advanced and MBC patients who were required to have received prior first or second-line chemotherapy. Among the 44 patients with PD-L1–positive disease across several MBC subtypes, the median overall survival was 26 months with the immunotherapy drug Durvalumab compared with 12 months with chemotherapy. For the “mixed” study population of patients with various breast cancer subtypes, the median overall survival was 21.7 months with Durvalumab vs. 17.9 months with chemotherapy.

MEDIOLA trial results

MEDIOLA Trial Results: Lynparza (Olaparib) plus Imfinzi (Durvalumab) in HER2 Negative BRCA Mutated MBC Patients –
MEDIOLA was a Phase 1/2 study evaluating the combination of Olaparib, an FDA-approved PARP inhibitor, with the immunotherapy drug Durvalumab in HER2 negative patients with advanced solid tumors harboring BRCA mutations. For MBC patients with hormone receptor-positive disease, the median progression-free survival (PFS) was 9.9 months, and the median overall response rate was 69.2%. By the number of prior lines of chemotherapy, the median PFS was 11.7 months for patients with 0 or 1 prior lines, and 6.5 months in those with 2 prior lines. Overall, patients exhibiting responses showed durable benefit, with a median duration of response of 9.2 months.

Verzenio (abemaciclib) for patients with brain metastases

Verzenio (Abemaciclib) for Patients with Brain Metastases – In a study of 58 hormone receptor-positive, HER2 negative MBC patients with brain metastases who took Verzenio, 52 were evaluable for evaluation of objective intracranial response rate (OIRR), the primary endpoint of this study. These patients had received a median of 4 prior systemic therapies in the metastatic setting. Three patients had a confirmed response for an OIRR of 6%, and 38% demonstrated a reduction in the sum of their intracranial targeted lesions. The intracranial clinical benefit rate, which consisted of patients with a response and those who had stable disease for at least 6 months, was 25%, and the median progression-free survival was 4.4 months.

If any of these trials look like they might apply to you, be sure to discuss them with your doctor or medical team!

Editor's Note: Here are 3 other articles in this series from SABC 2019 - Part 1, Part II, and Part III.

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