Last year ended with a potentially practice-changing trial in breast cancer, as trastuzumab emtansine (T-DM1, Kadcyla) significantly reduced invasive disease-free survival (iDFS) in patients with residual disease after neoadjuvant trastuzumab (Herceptin).
As reported at the 2018 San Antonio Breast Cancer Symposium (SABCS), patients randomized to T-DM1 had a 3-year iDFS of 88.3% versus 77% for patients who received additional trastuzumab. The difference translated into a 50% reduction in the hazard ratio for invasive recurrence or death (95% CI 0.39-0.64). Distant metastasis as the first invasive recurrence also occurred about 50% less often in the T-DM1 group (10.5% vs 15.9%).
“[This study] will likely form the foundation of a new standard of care in this population, and increase use of neoadjuvant therapy in HER2-positive early breast cancer,” said Charles Geyer Jr., MD, of Virginia Commonwealth University in Richmond.
The findings came from the multicenter KATHERINE trial involving almost 1,500 women with newly diagnosed, early-stage HER2-positive breast cancer. All of the patients received neoadjuvant therapy with a taxane and trastuzumab. Patients found to have residual invasive disease in the breast or axilla at surgery were randomized to adjuvant T-DM1 or trastuzumab. The primary endpoint was iDFS, defined as ipsilateral invasive recurrent, contralateral recurrence, distant recurrence, or death.
The trial was one of several recent studies that could have an impact on breast cancer care.
A low-dose adjuvant tamoxifen regimen proved feasible and appeared to reduce the risk of recurrence in patients with newly diagnosed hormone receptor-positive intraepithelial neoplasia, according to results of a placebo-controlled trial, also reported at SABCS.
After a median follow-up of 5.1 years, patients randomized to tamoxifen 5 mg daily for 3 years had 50% fewer breast cancer events as compared with the placebo group (14 vs 28, P=0.024). The low-dose therapy appeared to have systemic activity, as three patients in the tamoxifen arm developed contralateral invasive breast cancer versus 12 in the placebo group (P=0.018).
Women treated with tamoxifen had a small increase in hot flashes (P=0.05) but no differences from the placebo group with respect to daily hot flash score, vaginal dryness or pain during intercourse, or musculoskeletal pain. One patient in the tamoxifen arm developed endometrial cancer versus none in the placebo group.
“I think our study is practice changing because we show a great effect that is similar to what was seen with the standard dose in previous trials, but with much lower adverse side effects,” said Andrea De Censi, MD, of the the National Hospital E.O. Ospedali Galliera — S.C. Oncologia Medica in Genoa, Italy.
The study involved 500 women with intraepithelial neoplasia, a precursor lesion associated with an increased risk of invasive breast cancer. Investigators at 14 Italian centers randomized the patients to 5 mg tamoxifen or placebo for 3 years. The primary endpoint was any occurrence of invasive breast cancer.
Because the trial did not directly compare low-dose tamoxifen with the standard 20-mg dose, the study could not prove equivalence but “the data was pretty similar to the data with the 20-mg dose, as far as protecting against cancer,” said Virginia Kaklamani, MD, of UT San Antonio Health.
“This is pretty compelling and something I would try in my clinic,” she said.
Survival Bump with CDK4/6 Inhibitor
Continued follow-up of a randomized trial provided the best evidence to date that CDK4/6 inhibition can improve survival in advanced HR-positive breast cancer.
Long-term follow-up in the PALOMA-3 randomized trial showed a median overall survival of 34.9 months with the addition of palbociclib (Ibrance) to fulvestrant (Faslodex) versus 28.0 months with fulvestrant alone. That difference did not achieve statistical significance.
However, patients who previously responded to hormonal therapy had a statistically significant absolute improvement in median survival of 10 to 11 months with palbociclib, Massimo Cristofanilli, MD, of the Robert H. Lurie Comprehensive Cancer Center in Chicago, reported at the 2018 European Society for Medical Oncology congress.
Despite failing to meet the statistical target in the overall population, the almost 7-month improvement in survival will be viewed as clinically significant by most cancer specialists, he said.
“We now have solid data to suggest that this treatment should be the new standard of care,” Cristofanilli added.
The results strongly suggested that the previously reported progression-free survival (PFS) benefit with palbociclib will translate into a survival benefit, said Carmen Criscitiello, MD, PhD, of the European Cancer Institute in Milan. However, the trial lacked statistical power to demonstrate a survival difference.
“The other trials conducted with CDK 4/6 inhibitors will contribute to confirm the estimate of the survival benefit observed in this study,” she said.
Many Breast Cancer Patients May Skip Chemo
A breast cancer gene test may rule out the need for chemotherapy in as many as 70% of patients with HR-positive/HER2-negative breast cancer, results of a randomized trial suggested.
Data for 6,700 randomized patients with intermediate-risk scores on the Oncotype DX Breast Cancer Recurrence Test had nearly identical iDFS at 9 years whether they received chemotherapy plus hormonal therapy (84.3%) or hormonal therapy alone (83.3%). When combined with the 1,600 patients with low-risk scores, the results suggested that about 70% of women with early HR-positive/HER2-negative breast cancer could skip chemotherapy. For the remaining 1,300 patients with high-risk scores, chemotherapy would be indicated.
Application of the test in clinical practice, “would be expected to spare chemotherapy in about 70% of women and select chemotherapy in about 30%,” said Joseph Sparano, MD, of Albert Einstein Cancer Center in in New York City, at the 2018 American Society of Clinical Oncology meeting.
The trial results resolved a key issue in the use of the gene test in clinical decision-making. OncoType DX has a score range of 0-100. A score of ≤10 represented a low risk of recurrence, and a score ≥26 reflected tumors at high risk of recurrence. However, most patients have intermediate-risk scores of 10-25, for whom the need for chemotherapy remained controversial.
The reported results made for an “extraordinary day” for patients with HR-positive/HER2-negative breast cancer and the clinicians who care for them, said Harold Burstein, MD, of the Dana-Farber Cancer Institute in Boston.
“The vast majority of women who have this test performed on their tumor can be told they don’t need chemotherapy, and that can be said with tremendous confidence and reassurance,” he said.