Patients with chemotherapy-naïve, HER2-low hormone receptor-positive metastatic breast cancer experienced antitumor activity via combination therapy with Arimidex (anastrozole) or Faslodex (fulvestrant) plus Enhertu (fam-trastuzumab deruxtecan-nxki), according to data from the phase 1b DESTINY-Breast08 trial presented by Dr. Komal Jhaveri during the 2023 San Antonio Breast Cancer Symposium (SABCS).
Findings from the study showed that the 21 patients in the Enhertu plus Arimidex arm achieved a confirmed objective response rate (ORR; patients whose disease responded partially or completely to treatment) of 71.4% versus 40% for the 20 patients in the Enhertu plus Faslodex; the median duration of response (DOR) was 9.8 months in the Enhertu plus Arimidex arm and not evaluable in the Enhertu plus Faslodex arm.
The median progression-free survival (PFS; the time a patient lives without their disease worsening) was 13.4 months in the Arimidex arm and not evaluable in the Faslodex arm; six-month PFS rates were 80.7% and 75.3%, and the 12-month PFS rates were 50.4% and 52.7%, respectively.
Jhaveri noted that efficacy results should be interpreted with caution due to the small number of patients in each arm. Additionally, 15% of patients in the Enhertu plus Faslodex arm withdrew consent, discontinuing treatment before disease progression. The median follow-up was also slightly shorter in the Enhertu plus Faslodex arm at 15.2 months compared with 20.2 months in the Enhertu plus Arimidex arm.
The study enrolled patients with locally assessed HER-low hormone receptor-positive advanced or metastatic breast cancer. Patients could have received a maximum of one prior line of endocrine therapy with or without a targeted agent for metastatic disease; however, no prior chemotherapy in the metastatic setting was allowed. Additionally, patients needed to have one measurable lesion and an ECOG performance status of 0 or 1 (meaning they could perform daily tasks with little or no assistance).
Results from the dose-expansion phase were presented from the Enhertu plus Arimidex arm and the Enhertu plus Faslodex arm. Enhertu was administered every three weeks, Arimidex daily and Faslodex every four weeks.
An additional two arms of the trial examined Enhertu plus capecitabine or Truqap (capivasertib) in patients with hormone receptor-negative disease but were not presented at SABCS.
At baseline, patients in the Enhertu plus Arimidex arm had a median age of 55 compared with 65.5 in the Enhertu plus Faslodex arm. Patients had a HER2 status of IHC 1+ (76.2% versus 65%) or IHC 2+/ISH- (23.8 versus 35%); endocrine receptor (ER)-positive and progesterone receptor (PR)-positive (66.7% versus 50%), ER-positive and PR-negative (33.3% versus 45%) or ER-positive and PR missing (0% versus 5%) disease and an ECOG performance status of 0 (57.1% versus 85%), 1 (38.1% versus 15%) or 2 (4.8% versus 0%) in the Enhertu plus Arimidex arm versus Enhertu plus Faslodex arm, respectively.
“Safety evaluations were comparable to the safety (profile) of the individual agents alone,” Jhaveri, a breast oncologist and early drug development specialist at Memorial Sloan Kettering Cancer Center in New York, said during the presentation. “One patient (died) in (the) study and this was attributed to disease progression and drug-induced pneumonitis by the investigator, but per the adjudication committee, the interstitial lung disease (ILD) was not (determined) to be drug-induced. There were a total of five cases of drug-induced pneumonitis or ILD, all of which were grade 2. At the data cutoff, two had resolved, one was resolving and two were not resolved. Four of these five patients had at least one potential risk factor for developing ILD/pneumonitis.”
Regarding safety, common any-grade side effects observed in the Arimidex versus Faslodex arms included nausea (66.7% versus 95%), alopecia (42.9% versus 50%), fatigue (42.9% versus 15%), anemia (33.3% versus 25%), COVID-19 (33.3% versus 25%) and decreased appetite (33.3% versus 55%), among others. Side effects led to dose interruption (57.1% versus 45%), reduction (28.6% versus 20%) and discontinuation (19% versus 30%) of Enhertu, respectively.
Further, side effects of grade 3 or higher severity occurred in 47.6% versus 55% of patients in the Arimidex versus Faslodex arms, respectively.
The median actual treatment duration in the Arimidex arm was 10.4 months for Enhertu and 11 months for Arimidex. In the Faslodex arm, median actual treatment duration was 6.3 months for Enhertu and 8.3 months for Faslodex.
Additionally, 33.3% of patients in the Arimidex arm did not receive a prior line of treatment for metastatic disease compared with 30% of patients in the Faslodex arm. Investigators noted that as of Aug. 16, 2023, six patients were ongoing treatment in the Arimidex arm versus seven patients in the Faslodex arm; disease progression was the primary reason for treatment discontinuation.
“(Enhertu) in combination with (Arimidex) or (Faslodex) was active in chemotherapy-naive patients with HER2-low hormone receptor-positive metastatic breast, cancer demonstrating encouraging antitumor activity,” Jhaveri concluded. “However, these are small data sets that limit the interpretation of the efficacy results and further research to evaluate (Enhertu) in combination with endocrine therapies is warranted.”
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