The Targeted Pulse: Explore Highlighted Updates From This Year’s SABCS on Breast Cancer and ASH on Hematologic Cancers

Palbociclib Plus SOC Significantly Improved PFS in HR+, HER2+ Breast Cancer

First-line treatment with palbociclib (Ibrance) combined with standard-of-care therapy demonstrated a significant improvement in progression-free survival for patients with hormone receptor–positive, HER2-positive metastatic breast cancer. These results from the open-label, phase 3 AFT-38 PATINA trial (NCT02947685) were presented at the 2024 San Antonio Breast Cancer Symposium (SABCS) by Otto Metzger, MD, of Dana-Farber Cancer Institute, Boston, Massachusetts.

“Our results reinforce the strong scientific rationale for overcoming resistance to anti-HER2 therapy and endocrine therapy with the addition of palbociclib,” Metzger explained. “There is a strong rationale for blocking CDK4/6 in HER2-positive disease. The cyclin D1-CDK4 axis is essential for initiation and maintenance of growth in HER2-positive disease. The same axis drives resistance to the HER2 pathway blockade. This combined CDK4/6 and HER2 inhibition has shown to be synergistic and have a profound antitumor activity in preclinical models.”

Real-World Data Show No OS Difference Among CDK4/6 Inhibitors in mBC

No significant overall survival (OS) benefit was observed when comparing 3 CDK4/6 inhibitor combinations in hormone receptor-positive/HER2-negative metastatic breast cancer. Evaluated CDK4/6 inhibitor combinations included palbociclib (Ibrance) plus an aromatase inhibitor (AI), ribociclib (Kisqali) plus AI, and abemaciclib (Verzenio) plus AI.These real-world findings from the P-VERIFY (NCT06495164) retrospective study were presented at the 2024 SABCS.

“The P-VERIFY study suggests that there is no difference in OS among first-line CDK4/6 inhibitors and this would align with the PFS data that we have from those first-line studies,” Kari B. Wisinski, MD, professor of medicine at the University of Wisconsin Carbone Cancer Center in Madison, Wisconsin, explained in a presentation of the data. “However, the statistically OS beneficent that we have seen has only been with ribociclib. I think that longer follow-up would be very valuable and although real-world analyses have limitations it is unlikely that we will have a head-to-head study, and thus, these data add to the information that we have.”

Patritumab Deruxtecan Shows Efficacy With or Without Letrozole in HR+/HER2– BC

Patritumab deruxtecan (HER3-DXd) demonstrated a pathologic complete response (pCR) and objective response rate similar to multiagent chemotherapy in high-risk hormone receptor-positive, HER2-negative breast cancer irrespective of whether patients had added letrozole (Femara) or not. These data come from the phase 2 SOLTI VALENTINE trial, which were presented at 2024 SABCS.

“SOLTI VALENTINE supports the effectiveness of [patritumab deruxtecan] in early breast cancer and its potential incorporation in the treatment of high-risk HR-positive/HER2-negative breast cancer,” said Mafalda Oliveira, MD, PhD, of Vall d’Hebron University Hospital, Vall d’Hebron Institute of Oncology, and of the SOLTI Cancer Research Group, both in Barcelona, Spain, during the presentation. “The sample size was not selected to formally compare treatment arms in terms of pCR rate, but to achieve a certain level of precision estimating pCR in each arm,” he noted.

Cilta-Cel Elicited 100% CR for High-Risk Smoldering MM in a Phase 2 Trial

Ciltacabtagene autoleucel (cilta-cel; Carvykti) elicited a complete response (CR) in 100% of patients with high-risk smoldering multiple myeloma (MM), according to findings from a single-arm phase 2 trial (NCT05767359). Not only did patients achieve a complete response, but data also show that these responses deepened over time. The minimal residual disease (MRD)–negativity rate (10^-6) was also 100%, and none of the patients developed biochemical or SLIM-CRAB progression to date. SLIM-CRAB represents key diagnostic features of MM: S for serum monoclonal protein (M-protein); Li for light chain ratio (involved/uninvolved); M for multiple focal lesions on MRI; C for elevated calcium; R for renal dysfunction; A for anemia; and B for bone disease.

“The first 3 patients have sustained MRD negativity after 1 year of follow-up. The remainder of patients remain MRD negative at the time of their last follow-up.” said Omar Nadeem, MD, clinical director of the Center for Early Detection and Interception of Blood Cancers, and of the Myeloma Immune Effector Cell Therapy Program, at Dana-Farber Cancer Institute in Boston, Massachusetts, during the presentation at the 2024 ASH Annual Meeting and Exposition.

Selinexor/Ruxolitinib Showed Efficacy in Ruxolitinib-Pretreated Myelofibrosis

Selinexor (Xpovio) with ruxolitinib (Jakafi) demonstrated encouraging efficacy in patients with myelofibrosis (MF) who were previously treated with ruxolitinib, according to preliminary findings from the phase 2 SENTRY trial (NCT04562389). Efficacy was observed with both the 40 mg and 60 mg doses of selinexor evaluated, and the treatment exhibited a manageable safety profile. These data were presented by Minghui Duan, PhD, at the 2024 ASH Annual Meeting.

“Unlike the ESSENTIAL study [NCT03627403],” Duan began, which showed sustained spleen responses with selinexor as a single agent in MF refractory to a JAK inhibitor, “this combination of selinexor and ruxolitinib may achieve similar therapeutic effects without requiring higher doses.” He also noted that “patients with MF require more comprehensive methods for assessing efficacy than a 35% reduction in spleen volume or a 50% reduction in the total symptom score.”

Thank you for joining us for this week’s Targeted Pulse. Look out for more recaps to come.

In case you missed it, here is last week’s Targeted Pulse.