“Talimogene laherparepvec (T-VEC; Imlygic), an oncolytic viral immunotherapy approved for patients with melanoma, is being evaluated in a presurgical setting in a phase II clinical trial that may help set the stage for expanding the toolkit of neoadjuvant options for patients with the malignancy.
“Although new targeted and immunotherapy agents for patients with melanoma have been introduced in recent years in advanced and metastatic settings, there is a need for approaches that attack the disease earlier and prevent recurrence, said Robert H.I. Andtbacka, MD, the principal investigator for the T-VEC study. ‘I think it’s the next logical step for us to take in melanoma—to try to find better ways to activate the patient’s own immune system where the tumor is still in situ,’ Andtbacka said in an interview with OncLive. ‘Many of our colleagues in other tumor sites such as breast cancer and colon cancer have done this for many, many years, so we’ve been lagging a little bit behind in melanoma. But now I think we have good, effective therapies that we can start to ask these neoadjuvant questions.’ ”
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“Roughly 5 years ago, a study demonstrated that neoadjuvant endocrine therapy increases the rates of breast conservation surgery in patients with breast cancer as a result of the downstaging of disease.
“Now, an analysis of roughly 80,000 women with breast cancer in the United States shows that this study has done little to increase the use of this treatment modality.
” ‘Neoadjuvant endocrine therapy use has increased since the publication of Z1031 [the American College of Surgeons Oncology Group (ACOSOG) Z1031 study]. However, the overall rate of neoadjuvant endocrine therapy use is low, at 3.2%,’ said Akiko Chiba, MD, a breast surgery fellow at the Mayo Clinic, Rochester, Minnesota, who presented the study at the Society of Surgical Oncology (SSO) 2016 Cancer Symposium.”
“Treatment with the chemotherapy agent capecitabine increased disease-free survival for women with HER2-negative breast cancer that was not eliminated by presurgery chemotherapy, according to results from the phase III CREATE-X clinical trial presented at the 2015 San Antonio Breast Cancer Symposium, held Dec. 8-12.
“Treatment given to shrink or eliminate a tumor before surgery is called neoadjuvant therapy. In some patients with breast cancer treated with neoadjuvant chemotherapy, residual invasive cancer can be detected in breast tissue samples and lymph nodes removed during surgery. These patients tend to have worse long-term outcomes compared with women who respond completely to neoadjuvant therapy.
” ‘It has been suggested that patients with residual invasive disease after neoadjuvant chemotherapy have chemoresistant breast cancer, but there have been no large-scale clinical trials to test whether adjuvant systemic chemotherapy is beneficial for these patients,’ said Masakazu Toi, MD, PhD, a professor at Kyoto University Hospital in Japan, and founder and senior director of the Japan Breast Cancer Research Group (JBCRG). ‘CREATE-X was designed to evaluate this clinical question by testing whether capecitabine could improve disease-free survival for patients with residual invasive disease after neoadjuvant chemotherapy.’ “
“Dual HER2 blockade with trastuzumab and lapatinib was no better than trastuzumab alone in producing pathologic complete responses (pCR) in metastatic HER2-positive breast cancer patients in the neoadjuvant setting, according to a new study. Those with hormone receptor–negative disease did see an improvement with the dual blockade.
“ ‘In randomized neoadjuvant trials, dual HER2 targeting generally results in higher pCR rates, but the magnitude of this effect has varied,’ wrote study authors led by Lisa A. Carey, MD, of the University of North Carolina at Chapel Hill. The new trial was a three-arm study of preoperative therapy in 305 patients with stage II/III HER2-positive breast cancer; 118 patients were randomized to paclitaxel along with trastuzumab and lapatinib, 120 to paclitaxel with trastuzumab alone, and another 67 to paclitaxel along with only lapatinib. That last trial arm was closed early. Results were published online ahead of print in the Journal of Clinical Oncology.”
Women diagnosed with localized breast cancer face difficult decisions with their doctors. What kind of neoadjuvant (before surgery) treatment to choose? Should chemotherapy follow surgery? Based on the subtype of breast cancer, should specific chemotherapy drugs be used? Continue reading…
“Roche (SIX: RO, ROG; OTCQX: RHHBY) today announced that the European Commission (EC) has approved the use of Perjeta® (pertuzumab) in combination with Herceptin® (trastuzumab) and chemotherapy for the neoadjuvant treatment (use before surgery) of adult patients with HER2-positive, locally advanced, inflammatory, or early stage breast cancer at high risk of recurrence. The Perjeta regimen is the first neoadjuvant breast cancer treatment approved by the EC based on pCR data.
“Every year in Europe nearly 100,000 people are diagnosed with HER2-positive breast cancer, an aggressive type of the disease that is more likely to progress than HER2-negative cancer.1,2 Treating people with breast cancer early, before the cancer has spread, may improve the chance of preventing the disease from returning. Neoadjuvant treatment is given before surgery and is aimed at reducing tumour size so it is easier to surgically remove. pCR is achieved when there is no tumour tissue detectable at the time of surgery in the affected breast or in the affected breast and local lymph nodes. It is a common measure of neoadjuvant treatment effect in breast cancer and it can be assessed more quickly than traditional endpoints in eBC.
“ ‘Today’s approval is a significant milestone in the neoadjuvant treatment of HER2-positive early breast cancer, bringing Perjeta to patients years earlier than typical adjuvant treatment,’ said Sandra Horning, M.D., Roche’s Chief Medical Officer and Head, Global Product Development. ‘We are committed to making the Perjeta regimen available to appropriate patients in the EU as early as possible.’ “
“Chemotherapy-free neoadjuvant treatment with trastuzumab emtansine (T-DM1; Kadcyla) demonstrated a pathological complete response (pCR) rate of 40.5% in patients with HER2+ and HR+ early breast cancer, according to findings from the phase II ADAPT trial presented at the 2015 ASCO Annual Meeting.
” ‘After 12 weeks without systemic chemotherapies we observed more than a 40% pCR in both the breast and nodes in our T-DM1-treated HER+/HR+ patients,’ said lead investigator Nadia Harbeck, MD, PhD, head of the Breast Center, Oncological Therapy and Clinical Trials Unit, University of Munich, Germany. ‘We did see very low overall toxicity, and did not detect any new safety signals.’
“The ADAPT trial is a large umbrella trial that has enrolled 5000 patients with various breast cancer phenotypes. In the arm of the trial presented at ASCO, 376 patients with HER2+ and HR+ breast cancer were randomized to receive neoadjuvant T-DM1 at 3.6 mg/kg with or without endocrine therapy or trastuzumab plus endocrine therapy. Treatment was administered for 4 cycles followed by surgery and 1-year of standard adjuvant chemotherapy plus trastuzumab.”
“In an analysis of the NeoALTTO trial reported in JAMA Oncology, Salgado et al found that a higher level of tumor-infiltrating lymphocytes was associated with improved pathologic compete response rate and event-free survival independent of neoadjuvant treatment received in patients with HER2-positive early breast cancer.
“In NeoALTTO, 455 patients were randomly assigned to receive neoadjuvant trastuzumab (Herceptin), lapatinib (Tykerb), or the combination for 6 weeks followed by the addition of weekly paclitaxel for 12 weeks and three cycles of fluorouracil, epirubicin, and cyclophosphamide after surgery. Percentage of tumor-infiltrating lymphocytes were measured by hematoxylin-eosin stained core biopsy sections taken at diagnosis.”
“The German Breast Group (GBG) presented two analyses that can serve as predictors of response to treatment by further subdividing preoperative (neoadjuvant) patients with HER 2 positive breast cancer and those with triple negative breast cancer based on tumor DNA repair capabilities and related factors.
“Prof. Dr. Gunter von Minckwitz, president of the GBG Research Institute, noted, ‘Taken together these studies demonstrate that a deeper understanding of the variations among breast cancer types that go beyond hormone response and BRCA gene mutations can inform treatment options with increased precision.’
“One study (Abstract No: 1004) fromlead author Dr. von Minckwitz found cancer-related BRCA mutations in the tumor are more common (30.3%) than inherited BRCA mutations (19.8%) in patients with triple-negative breast cancer. The homologous recombination (HR) assay measures DNA repair capacity beyond those related to BRCA mutation. HR deficiency defined as having either a BRCA mutation of the tumor or a high HR score was found in 70.5% of the patients. These findings can affect treatment options. Patients with a tumor BRCA mutation and/or a high HR score showed a high complete response to preoperative (neoadjuvant) chemotherapy. Our findings suggest those patients are also benefiting more from the additional use of carboplatin than tumors without HR deficiency.”