Negative study that documents failure of accretive benefit of TDM1/pertuzumab over trastuzumab/pertuzumab. Exploration of other pathways or target/payload will be necessary for clinical improvement/risk reduction of recurrence.
We aimed to improve efficacy and reduce toxicity of high-risk human epidermal growth factor receptor 2 (HER2)–positive early breast cancer (EBC) treatment by replacing taxanes and trastuzumab with trastuzumab emtansine (T-DM1).
The phase III KAITLIN study (NCT01966471) included adults with excised HER2-positive EBC (node-positive or node-negative, hormone receptor–negative, and tumor > 2.0 cm). Postsurgery, patients were randomly assigned 1:1 to anthracycline-based chemotherapy (three-four cycles) and then 18 cycles of T-DM1 plus pertuzumab (AC-KP) or taxane (three-four cycles) plus trastuzumab plus pertuzumab (AC-THP). Adjuvant radiotherapy/endocrine therapy was permitted. Coprimary end points were invasive disease-free survival (IDFS) in the intention-to-treat node-positive and overall populations with hierarchical testing.
The median follow-up was 57.1 months (interquartile range, 52.1-60.1 months) for AC-THP (n = 918) and 57.0 months (interquartile range, 52.1-59.8 months) for AC-KP (n = 928). There was no significant IDFS difference between arms in the node-positive (n = 1,658; stratified hazard ratio [HR], 0.97; 95% CI, 0.71 to 1.32) or overall population (n = 1846; stratified HR, 0.98; 95% CI, 0.72 to 1.32). In the overall population, the three-year IDFS was 94.2% (95% CI, 92.7 to 95.8) for AC-THP and 93.1% (95% CI, 91.4 to 94.7) for AC-KP. Treatment completion rates (ie, 18 cycles) were 88.4% for AC-THP and 65.0% for AC-KP (difference driven by T-DM1 discontinuation because of laboratory abnormalities [12.5%]). Similar rates of grade ≥ 3 (55.4% v 51.8%) and serious adverse events (23.3% v 21.4%) occurred with AC-THP and AC-KP, respectively. KP decreased clinically meaningful deterioration in global health status versus THP (stratified HR, 0.71; 95% CI, 0.62 to 0.80).
The primary end point was not met. Both arms achieved favorable IDFS. Trastuzumab plus pertuzumab plus chemotherapy remains the standard of care for high-risk HER2-positive EBC.
It seems donepezil did not show any cognitive benefit when added to standard adjuvant chemotherapy for breast cancer. Unfortunately, adequate treatment for ‘chemo-brain’ remains elusive. There is data that a lipid structure, S1P, may be linked to this process and may be ‘druggable’ with some of the MS agents.
Datopotamab Deruxtecan is a new ADC that will likely be approved in the near future. The payload is the same as used in Enhertu, but the antibody is directed at TROP2. This report is from the TROPION-pan tumor study and shows a promising ORR in HR+/HER2- MBC. There is reasonable data for this compound in 2L met-NSCLC in the TROPION-LUNG01 study with an improvement in PFS compared to docetaxel of 4.4 vs 3.7 months. Dato also is effective in patients with actionable genetic alterations in the 2L setting. There is also an ongoing study on its use in the 1L setting for met-NSCLC in combination with pembrolizumab and chemotherapy.
Nicely done study comparing Ribociclib + ET vs chemotherapy in premenopausal high-risk HR+, HER2-neg patients felt to be high risk. Results showed better efficacy (PFS), tolerability and similar response rates. Of note, >80% of patients had visceral disease or were felt to be rapid progressors. Anti-hormone-based therapy remains king in the HR+ setting.
Noteworthy NCCI database study showing zip code has a negative influence on tumor burden and outcomes. I wonder if the presence of community oncology practices in similar geographical zones reduces this interaction of environmental opportunity and outcomes.
Findings from the PACE study show that the addition of Palbociclib to Fulvestrant was not better than Fulvestrant alone, and the addition of Avelumab to Fulvestrant improved and nearly doubled the PFS. This is compelling and should be studied further for our patients with HR+ HER2- MBC.
FCS Hematology Oncology Review creates a platform for our physician network to observe the most recent articles and studies available in the oncology and hematology world. By sharing these articles we are building our wealth of knowledge of new observations and treatments as they come available.
