The past year brought the breast cancer community a CDK inhibitor for early-setting disease, the combination of a PD-1 inhibitor and preoperative chemotherapy in advanced disease, trastuzumab monotherapy for some older patients, third-line antibody-drug conjugate (ADC) therapy instead of chemo, and data on the risks posed by interval-detected breast cancers.
Adjuvant CDK4/6 Inhibitor Thwarts Recurrence
Adding a CDK4/6 inhibitor to adjuvant therapy for high-risk breast cancer significantly increased the disease-free interval, according to a randomized trial.
The hazard for invasive disease-free survival (iDFS) declined by 25.3% in women who received abemaciclib (Verzenio) in addition to standard endocrine therapy. The relative risk for metastatic recurrence decreased by almost 30% with the combination as compared with endocrine therapy.
“Abemaciclib is the first CDK inhibitor to show a significant improvement in the early breast cancer setting, when combined with endocrine therapy, as compared with endocrine therapy alone,” Stephen R. D. Johnston, MD, of the Royal Marsden Hospital in London, said during the European Society for Medical Oncology (ESMO) virtual congress. “The results indicate the prevention of early recurrence and a clinically meaningful reduction in the risk of distant recurrence.”
The findings came from a randomized trial involving 5,637 patients with early-stage, high-risk hormone receptor-positive/HER2-negative breast cancer. All patients received physician’s choice of standard endocrine therapy for 5 to 10 years, with or without 2 years of adjuvant abemaciclib. The primary endpoint was iDFS.
The results have potentially practice-changing implications but require longer follow-up to determine whether the iDFS benefit translates into improved overall survival, said Giuseppe Curigliano, MD, of the National Cancer Institute of Milan, who was not involved in the trial.
Big Jump in pCR Rate With Add-On Anti-PD-1
Escalating neoadjuvant therapy, with the addition of a PD-1 inhibitor to chemotherapy, more than doubled the rate of pathologic complete response (pCR) in women with early-stage breast cancer, results of a phase II clinical trial showed.
The pCR rate increased from 17% with chemotherapy alone to 44% in women who also received pembrolizumab (Keytruda) prior to surgery. Among patients with triple-negative breast cancer (TNBC), pCR occurred in 6o% of patients treated with pembrolizumab and chemotherapy. Residual disease burden also declined in patients who received the add-on immunotherapy, reported Rita Nanda, MD, of the University of Chicago, and colleagues JAMA Oncology.
Emphasizing that preliminary nature of the trial, the authors point out that positive early data previously reported from the phase III KEYNOTE 522 trial provided strong supporting evidence for the strategy of combining immunotherapy with preoperative chemotherapy. Two thirds of patients with TNBC achieved pCR after chemotherapy plus pembrolizumab before surgery.
Skip Chemo for Some Older Patients With HER2 Disease?
A technically negative clinical trial nonetheless made a case for omitting chemotherapy from treatment for selected older patients with early-stage HER2-positive breast cancer, Japanese investigators suggested in the Journal of Clinical Oncology.
A randomized trial showed a 4.3% absolute difference in disease-free survival (DFS) with trastuzumab (Herceptin) alone versus trastuzumab plus chemotherapy. The difference translated into a nonsignificant hazard ratio (HR) of 1.36 (95% CI 0.72-2.58). Prespecified statistical considerations for noninferiority established an upper confidence limit of 1.69.
However, a supplementary analysis showed a survival loss of less than 1 month at 3 years for patients who received only trastuzumab. Investigators calculated restricted mean survival time (RMST) for each treatment arm. That analysis resulted in a DFS difference of -0.39 months at 3 years with trastuzumab alone. An RMST analysis for relapse-free survival (95.3% with chemotherapy, 92.4% without) yielded a 3-year difference of -0.41 months.
Chemotherapy was associated with a 70.6% incidence of grade 3/4 adverse events, and almost all types and grades of adverse events occurred more often in the chemotherapy arm.
“In light of the lower toxicity and more favorable HRQoL [health-related quality of life] profile, trastuzumab monotherapy can be considered as an adjuvant therapy option for selected older patients,” Masataka Sawaki, MD, PhD, of Aichi Cancer Center Hospital in Nagoya, and colleagues concluded.
The findings came from a phase III randomized trial involving 266 patients with a median age of 73.5.
ADC Slows Metastatic TNBC
Patients with metastatic TNBC lived more than three times as long without disease progression when they received the ADC sacituzumab govitecan (Trodelvy) instead of chemotherapy as third-line therapy, findings from a phase III trial showed.
Median progression-free survival increased from 1.7 months with chemotherapy to 5.6 months with the ADC. The difference represented almost a 60% reduction in the hazard for disease progression or death, reported Aditya Bardia, MD, of Massachusetts General Hospital Cancer Center in Boston, during the ESMO virtual meeting.
The trial, involving 529 patients with TNBC from seven countries, showed that treatment with sacituzumab govitecan led to a higher response rate (35% vs 5%) and higher clinical benefit rate (45% vs 9%).
“The clinical benefit here confirms the use of sacituzumab govitecan as a standard therapy for patients with pretreated metastatic triple-negative breast cancer,” Bardia said.
Ominous Nature of Interval-Detected Cancers Affirmed
Breast cancers detected between routine mammographic screenings (interval detection) conferred a significantly higher risk for aggressiveness and death, a retrospective study from Canada showed.
During a median follow-up of 7 years, women with interval-detected breast cancers were more than three times as likely to die of breast cancer (HR 3.55, 95% CI 2.01-6.28, P<0.001). As compared with cancers identified during screening, interval cancers had significantly higher odds ratios (OR) for high-grade disease (OR 6.33 for grade III vs grade 1, 95% CI 3.73-10.75, P<0.001) and negative estrogen-receptor status (OR 2.88, 95% CI 2.01-4.13, P<0.001).
The findings highlighted the differences in the natural history of interval-detected cancers, as well as “inadequacies in current breast cancer screening practice,” reported Saroj Niraula, MD, of the University of Manitoba in Winnipeg, and colleagues in JAMA Open Network. “Many of the aggressive and lethal forms of breast cancers either go unnoticed on mammogram or develop in the interval between mammograms.”
The analysis included 69,025 women who underwent a total of 212,579 mammograms during 2004 to 2010. Of 1,687 breast cancers diagnosed, 705 were screen detected, 206 were interval detected (within 2 years of a normal mammogram), 275 involved noncompliant patients (>2 years since last mammogram), and 501 involved women outside the screening program. Of 170 breast cancer deaths, 20 were in the screen-detected group, 29 in the interval group, 27 in the noncompliant group, and 94 in women outside the screening program.
Other developments in breast cancer:
Last Updated December 07, 2020