Azka Ali, MD, is a medical oncologist in the Department Hematology and Medical Oncology at the Cleveland Clinic Taussig Cancer Institute. 

Dr Ali on the Efficacy of CDK4/6 Inhibition in ER+, HER2+ Breast Cancer

“Agents like CDK4/6 inhibitors—palbociclib specifically, which is what [was] used in PATINA—are going to improve disease outcomes in those patients who [have] HER2-positive [disease] that is also ER [positive].”

Azka Ali, MD, a medical oncologist in the Department of Hematology and Medical Oncology at the Cleveland Clinic Taussig Cancer Institute, discussed clinical trial data that have informed the role of CDK4/6 inhibition in patients with estrogen receptor (ER)–positive breast cancer, including those with HER2-positive disease.

Both the phase 3 monarchE (NCT03155997) and PATINA (NCT02947685) trials have helped guide the use of CDK4/6 inhibitors for patients with several breast cancer subtypes. The monarchE trial investigated adjuvant abemaciclib (Verzenio) plus endocrine therapy in patients with ER-positive, HER2-negative, high-risk early breast cancer. This trial showed that 2 years of adjuvant abemaciclib plus endocrine therapy improved invasive disease–free survival, distant relapse–free survival, and overall survival in this population compared with endocrine therapy alone.

In contrast, the PATINA trial evaluated palbociclib plus standard-of-care maintenance therapy in patients with ER-positive, HER2-negative breast cancer. PATINA showed that the addition of palbociclib to first-line maintenance anti-HER2 and endocrine therapy following induction chemotherapy resulted in a statistically significant and clinically meaningful progression-free survival (PFS) improvement compared with anti-HER2 therapy and endocrine therapy alone in this patient population. The median PFS was 44.3 months (95% CI, 32.4-60.9) in the palbociclib arm vs 29.1 months (95% CI, 23.3-38.6) in the control arm (HR, 0.74; 95% CI, 0.58-0.94; unstratified 1-sided 

The findings from these 2 trials collectively suggest that CDK4/6 inhibitors play a significant role in the management of ER-positive breast cancer, and that this role is likely independent of HER2 status, according to Ali. In HER2-positive breast cancer, targeting the HER2 pathway with monoclonal antibodies remains essential for disease control, she explained. However, the results from PATINA indicate that CDK4/6 inhibitors—specifically palbociclib—may further enhance clinical outcomes in patients with both HER2-negative and ER-positive disease, she concluded.

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Azka Ali, MD, discusses how data from the PATINA trial inform the role of CDK4/6 inhibition in ER-positive, HER2-positive breast cancer.

Dr Ali on the Potential SOC Role of Palbociclib Plus Anti-HER2 and Endocrine Therapy in HER2+ Breast Cancer  

"What we're seeing is a 15-month improvement in PFS [with palbociclib plus SOC anti-HER2 and endocrine therapy vs the SOC] in that first-line [setting]. The data look very exciting. We await more information on this study, and hopefully an FDA approval."

Azka Ali, MD, a medical oncologist in the Department Hematology and Medical Oncology at the Cleveland Clinic Taussig Cancer Institute, discusses how findings from the phase 3 AFT-38 PATINA trial (NCT02947685) support the addition of palbociclib (Ibrance) to anti-HER2 and endocrine therapy as a new standard of care (SOC) in the maintenance setting for patients with hormone receptor–positive, HER2-positive metastatic breast cancer.

, the addition of palbociclib to SOC trastuzumab (Herceptin) with or without pertuzumab (Perjeta) and endocrine therapy produced a statistically significant and clinically meaningful improvement in progression-free survival (PFS) in this patient population in the first-line maintenance setting, Ali reported. The palbociclib regimen (n = 261) resulted in a median PFS of 44.3 months (95% CI, 32.4-60.9) compared with 29.1 months (95% CI, 23.3-38.6) for SOC therapy alone (n = 257; HR, 0.74; 95% CI, 0.58-0.94; unstratified 1-sided 

 = .0074). The median follow-up was 52.6 months among patients who remained alive and disease free.

Subgroup analyses of PFS also favored the addition of palbociclib across clinically relevant cohorts. Among patients with prior exposure to anti-HER2 therapy, the HR for PFS was 0.76 (95% CI, 0.57-1.01); among those without prior anti-HER2 exposure, the HR was 0.68 (95% CI, 0.54-1.07).

These data suggest that the addition of palbociclib to anti-HER2 therapy and endocrine therapy may represent a potential new SOC in the maintenance setting for patients with hormone receptor–positive, HER2-positive disease, Ali asserted. Ongoing follow-up is anticipated, and regulatory review will further inform the clinical utility of this regimen in routine practice, Ali concluded.

Azka Ali, MD, discusses the use of palbociclib to overcome resistance to anti-HER2 and endocrine therapies in HER2-positive breast cancer.

Dr Ali on the Potential SOC Role of Palbociclib Plus Anti-HER2 and Endocrine Therapy in HER2+ Breast Cancer

Dr Ali on the S0221 Trial of Alternative Chemo Dosing Schedules in Breast Cancer

Azka Ali, MD, medical oncologist, Cleveland Clinic Taussig Cancer Institute, discusses updated findings from the phase 3 S0221 trial (NCT00070564) investigating alternative adjuvant anthracycline and taxane dosing schedules in patients with high-risk, early breast cancer.

Azka Ali, MD, discusses findings from the S0221 trial of alternative adjuvant anthracycline and taxane dosing schedules in high-risk, early breast cancer.

Azka Ali, MD

Articles

Dr Ali on the Efficacy of CDK4/6 Inhibition in ER+, HER2+ Breast Cancer

Dr Ali on the Potential SOC Role of Palbociclib Plus Anti-HER2 and Endocrine Therapy in HER2+ Breast Cancer

Dr Ali on the S0221 Trial of Alternative Chemo Dosing Schedules in Breast Cancer