Treatment with neratinib (Nerlynx) or ado-trastuzumab emtansine (T-DM1; Kadcyla) in the adjuvant setting was found to reduce the risk of recurrence in an epidemiologic model of HER2-positive, early-stage breast cancer compared with other therapies, according to data presented during the 2021 San Antonio Breast Cancer Symposium.

Of patients with early-stage breast cancer, 15% to 20% will be HER2-positive. HER2-positivity is associated with more aggressive disease and an increased risk of recurrences. Currently, the standard of care is 1 year of trastuzumab with chemotherapy. Up to 24% of patients experience recurrence, according to data from long-term follow-up studies. The median follow-up was 11 years.

The APHINITY (NCT01358877), KATHERINE (NCT01772472), and the ExteNET (NCT00878709) trials showed the benefits of adjuvant and extended adjuvant treatments for preventing recurrence. However, patient population heterogeneity and different study designs make cross comparison difficult.

Investigators developed an epidemiologic model to simulate distant recurrence for 1000 patients with newly diagnosed HER2-positive early-stage breast cancer in all 3 trials. ExteNET evaluated neratinib vs placebo in the extended adjuvant setting in patients treated with trastuzumab (Herceptin)-based therapy within 12 months between 2009 and 2012. The APHINITY trial looked at pertuzumab plus trastuzumab vs placebo plus trastuzumab plus standard adjuvant chemotherapy in patients without neoadjuvant therapy treated between 2011 and 2014. The KATHERINE study looked at a T-DM1 vs trastuzumab in patients with pathological complete response following neoadjuvant therapy treated between 2013 and 2016.

Disease-free survival cursed from the trials were used to estimate the risk of distant recurrence when available. For the 2 subgroup analyses where they were missing, invasive disease-free survival curves were used. Both observed and estimated curves were extrapolated to the standard 10-year follow-up period. Additionally, investigators assumed that prevention of recurrence did not continue beyond the follow-up period.

The model’s outputs were distant recurrence for the treatment and control arms for each study and the avoided distant recurrence in the treatment and control arms.

The analysis found that the higher-risk populations had a greater absolute benefit of treatment. Over the 10-year time horizon, distant recurrences avoided per 1000 women ranged from 11 to 65. The no pathological complete response (pCR) in the intent-to-treat (ITT) and the no pCR HR-positive populations of the KATHERINE study and the no pCR/HR-positive population of the ExteNET study had the greatest modeled absolute treatment benefit.

In the ExteNET study’s ITT population, of the 143 events in the control arm, 18 distant recurrences were avoided. In the APHINITY’s study ITT population, of the 103 events in the control arm, 20 distant recurrences were avoided. In the ExteNET’s study HR-positive arm, of the 148 events in the control arm at baseline, 27 distant recurrences were avoided. In the HR-positive population of the Aphinity study, of the 61 events in the control arm, 11 distant recurrences were avoided.

In the KATHERINE study’s no pCR/ITT population, of the 255 events in the control arm, 64 distant recurrences were avoided. In the no pCR/HR-positive population, of the 239 events in the control arm, 41 distant recurrences were avoided. Similarly, in ExteNET’s no pCR/HR-positive population, of the 265 events at baseline, 65 distant recurrences were avoided.

Overall, a range of reductions in distant recurrence from HER2-targeted agents was observed. The analysis is ongoing to quantify the uncertainty of the modeled estimates. However, being able to estimate absolute treatment benefit over a standardized timeframe can help to better understand benefits across heterogeneous breast cancer trials.

Veenstra D, Hendrix N, Dolan C, et al. Estimating the long-term risk of recurrence in patients receiving HER2-targeted agents in HER2+ early-stage breast cancer. Presented at: 2021 San Antonio Breast Cancer Symposium; December 7-10, 2021; San Antonio, TX. Abstract P2-11-19.

Articles

The introduction of adjuvant approaches reduced the risk of disease recurrence in HER2-positive, early-stage breast cancer.

Adjuvant Neratinib or T-DM1 Decreases Distant Recurrence Risk in HER2+ Early-Stage Breast Cancer

Despite most patients with cancer preferring to die at home, about a third still die in the hospital, with about 10% being in the intensive care unit (ICU), causing more pain and anxiety to the patient and increasing the risk of post-traumatic stress disorder and prolonged grief disorder for family and caregivers, according to a new study published in BMC Cancer.   

Not only do many patients die in the hospital, an estimated 30% of late-stage patients will be offered chemotherapy in the last few months of life, according to the study. This number is on the rise, as is emergency room visits, admission to the ICU, and hospitalizations. In addition, study authors also noted that clinicians often lack the knowledge of their patients wishes regarding hospital resuscitation.   

The study, titled, “Breaking silence: a survey of barriers to goals of care discussions from the perspective of oncology practitioners” found that less than a third of patients with advanced cancer had a goals-of-care conversation with a member of their care team.  

The study was conducted by sending a survey to 185 oncology clinicians, 30 staff oncologists, 10 oncology residents, and 28 oncology nurses. The survey used a 7-point Likert scale where respondents assessed barriers to goal-of-care discussions.  

Researchers found that the patients and family are the biggest barrier to goals-of-care discussions. The study states, “these included: family member's difficult accepting a poor prognosis, lack of family agreement in the goals of care, difficulty understanding the limitations of life- sustaining treatments, lack of patients capacity to make goals of care decisions, and language barriers.” System and healthcare factors were perceived as less important.  

“While GoC discussions improve the dying experience for patients, this study adds to the literature demonstrating that patients and family factors are the biggest barriers to effective GoC discussions as perceived by clinicians,” the study states.  

Researchers found that care teams should make time over the course of the entire illness for goals-of-care discussions. Due to the denial and anxiety many patients may have regarding their illness, the discussions should be led by physicians and nurses who have strong communication skills and who have received training. The study also found that participants think social workers can also initiate goals of care discussions.  

The study faced several limitations such as low response rate, small sample size, and that most respondents were residents and relatively young. However, the findings were similar to a larger study conducted on medical wards, according to the report. 

“Other studies have found that oncology practitioners often lack communication skills training and have discomfort with difficult discussions that include mortality acknowledgement and the introduction of a palliative care approach to care,” the study states. 

Despite most wishing to die at home, nearly a third of patients with cancer die in the hospital. Goals-of-care discussions with nurses and other providers can help bring that number down.

Sara Karlovitch

Articles

Adjuvant Neratinib or T-DM1 Decreases Distant Recurrence Risk in HER2+ Early-Stage Breast Cancer

End-of-Life Discussions Reduce Patient Anxiety, Discomfort in Cancer Care