“High levels of tumor-infiltrating lymphocytes served as an independent positive predictive marker for EFS and pathological complete response in HER-2–positive early breast cancer treated with chemotherapy and anti-HER–2 agents, according a secondary analysis of the NeoALTTO trial.
“ ‘Increasingly, oncogenic addiction, in which tumors become dependent on a sole oncogenic pathway for growth, is thought to promote a tumor microenvironment conducive to immune escape,’ Sherene Loi, MD, PhD, of the Peter MacCallum Cancer Centre at the University of Melbourne, and colleagues wrote. ‘Although this had not been shown yet for HER-2 oncogenic signaling, one could speculate that anti-HER–2 therapy may not only work in a cell-intrinsic manner but may also reserve HER-2–induced immunosuppression as a mechanism for action.’
“The NeoALTTO trial included 455 women with HER-2–positive early-stage breast cancer between 2008 and 2010. The researchers randomly assigned patients to neoadjuvant treatment with trastuzumab (Herceptin, Genentech), lapatinib (Tykerb, GlaxoSmithKline) or both.
“Patients received the initial treatment for 6 weeks, followed by weekly paclitaxel for 12 weeks and three treatment cycles of fluorouracil, epirubicin and cyclophosphamide after surgery.”
“Erlotinib showed promise as neoadjuvant therapy in patients with epidermal growth factor receptor (EGFR) mutant stage IIIA-N2 non-small-cell lung cancer (NSCLC) who demonstrated good disease control with tolerable toxicity following treatment.
“Dr Baohui Han, Pulmonary Department, Shanghai Chest Hospital, Shanghai, China presented findings from a single arm, phase II clinical trial during the New Treatment Avenues Proffered Papers session at the European Lung Cancer Conference, 15 to 18 April 2015 in Geneva, Switzerland. The trial aimed to evaluate efficacy and safety of erlotinib as neoadjuvant treatment in patients with stage IIIA-N2 NSCLC and activating EGFR mutation.
“The trial’s primary endpoint was radical resection rate. Secondary endpoints included pathological complete response rate (pCR), objective response rate (ORR), disease free survival (DFS), overall survival (OS), safety profile, and explorative biomarkers.
“This study screened 155 patients and subsequently enrolled 44 patients with stage IIIA N2 NSCLC and 25 patients with IIIA N2 NSCLC plus activating EGFR (exon 19 or 21) mutations. All patients had ECOG performance status 1 and had been previously untreated for stage IIIA-N2 NSCLC, that was confirmed by endobronchial ultrasound.”
“Patients with larger malignant tumors of the breast who undergo chemotherapy before a breast cancer operation are more likely to undergo a lumpectomy than a mastectomy, according to a study published by Killelea et al in the Journal of the American College of Surgeons.
“ ‘Going forward, it will be interesting to see whether or not the use of neoadjuvant therapy continues to rise as newer drugs and agents are being developed all the time,’ Dr. Killelea said. ‘It will also be interesting to watch what happens to the rate of breast conservation over time. We don’t know. That’s why it’s so important for us to have a database like NCDB.’ ”
“In a study reported in the Journal of Clinical Oncology, Denkert et al found that increased tumor-infiltrating lymphocytes and the presence of lymphocyte-predominant breast cancer were associated with increased rates of pathologic complete response in patients receiving neoadjuvant anthracycline-taxane treatment with or without carboplatin. Higher rates were observed with carboplatin, with treatment interactions being significant among all patients and among those with HER2-positive disease but not among those with triple-negative disease. mRNA profiles for immune-related genes also distinguished pathologic complete response rates.
“The study involved 580 tumors from patients in the GeparSixto trial, which assessed the effects on pathologic complete response rates of adding carboplatin to neoadjuvant anthracycline plus taxane treatment. The current analysis assessed the effects on pathologic complete response of tumor-infiltrating lymphocyte levels, the presence of lymphocyte–predominant disease, and levels of immune-activating (CXCL9, CCL5, CD8A, CD80, CXCL13, IGKC, CD21) and immunosuppressive genes (IDO1, PD-1, PD-L1, CTLA4, FOXP3).”
The gist: Women with HER2-positive breast cancer whose tumors also have a mutation called PIK3CA might not respond as well to HER2-targeted treatments. Scientists looked at tumor samples from patients who had taken the drugs trastuzumab (Herceptin) and/or lapatinib (Tykerb). They had also taken neoadjuvant (before surgery) chemotherapy. Patients whose tumors had PIK3CA mutations had a significantly lower rate of treatment success. These findings highlight the need for more research into PIK3CA-targeted therapy. They also echo findings from other researchers.
“Patients with HER-2–positive breast cancer who harbored activating mutations in PIK3CA were considerably less likely to achieve total pathologic complete response to neoadjuvant HER-2–targeted therapies than patients who did not have PIK3CA mutations, according to findings in the randomized, phase 3 NeoALTTO trial.
“PIK3CA activating mutations are present in all subtypes of breast cancer. However, they are enriched in HER-2–positive and ER-positive disease, according to study background.
“José Baselga, MD, PhD, physician-in-chief and chief medical officer at Memorial Sloan Kettering Cancer Center, and colleagues investigated whether an association existed between PIK3CA mutation status and patients’ response to HER-2–targeted therapy.”
The gist: Recent research found that prostate cancer patients have similar survival rates whether they have androgen deprivation therapy (ADT) before or after tumor-removal surgery. The study focused on men with intermediate- or high-risk prostate cancer who were treated between 1995 and 2002.
“Patients with intermediate- or high-risk prostate cancer demonstrated similar biochemical relapse-free survival, distant metastasis-free survival and OS regardless of whether they received androgen deprivation in the neoadjuvant or adjuvant settings, according to study results.
“Patients with localized prostate cancer typically undergo androgen deprivation therapy (ADT) in the neoadjuvant setting, concurrent with radiation therapy.
“Michael A. Weller, MD,of Cleveland Clinic, and colleagues assessed whether patients who underwent ADT in the adjuvant setting experienced different outcomes.
“The analysis included 515 patients treated with radiation therapy and ADT from 1995 to 2002. Of these patients, 311 underwent ADT in the neoadjuvant setting, beginning 2 to 3 months before the start of radiation therapy. The other 204 patients underwent ADT in the adjuvant setting, immediately after the completion of radiation therapy.”
Pertuzumab (Perjeta) is a relatively new drug that targets HER2, a protein found at higher-than-normal levels in about 15% to 20% of all breast cancers. Too much HER2 leads to tumor growth. Currently, all newly diagnosed breast cancer patients have their tumors’ HER2 levels tested. Knowing whether a patient’s HER2 levels are abnormally high (HER2-positive) or normal (HER2-negative) is a major factor in choosing a treatment, thanks to the availability of trastuzumab (Herceptin) and, now, other HER2-targeted drugs such as Perjeta, T-DM1 (Kadcyla), and lapatinib (Tykerb). These drugs are all used to treat HER2-positive patients. Continue reading…
The gist: Breast cancer patients being treated with the drug trastuzumab (Herceptin) receive the same benefits whether they take it intravenously (by IV) or as an injection.
“Subcutaneous trastuzumab demonstrated comparable safety and efficacy to IV trastuzumab in patients with HER-2–positive early breast cancer, according to results of an international randomized, open-label phase 3 study.
“Christian Jackisch, MD, PhD, of the Breast Cancer and Gynecology Cancer Center at Sana Klinikum Offenbach GmbH in Germany, and colleagues compared the pharmacokinetics, efficacy and safety of subcutaneous vs. IV trastuzumab (Herceptin, Genentech). The study included 596 women with HER-2–positive, operable, locally advanced or inflammatory breast cancer in the neoadjuvant/adjuvant setting.
“All women underwent treatment with eight cycles of neoadjuvant chemotherapy administered concurrently with trastuzumab. Trastuzumab was administered either via 3-weekly fixed doses of 600 mg or via the standard weight-based method.
“Patients continued treatment with trastuzumab for 1 year after surgery.”
The gist: Many women with HER2-positive breast cancer take the drug trastuzumab (aka Herceptin) along with chemotherapy after tumor-removal surgery to keep the cancer from returning. However, new research shows that women who have high levels of certain immune system cells in their tumors might not benefit from Herceptin. For these patients, chemotherapy might be just as effective at preventing the return of cancer as the chemo/Herceptin combo.
“HER2-positive breast cancers with a high level of immune cell infiltration might not benefit from the addition of trastuzumab (Herceptin) to chemotherapy, a trial analysis suggested.
“The 10% of patients with stromal tumor-infiltrating lymphocyte-predominant breast cancer in the Alliance N9831 trial showed similar recurrence-free survival (RFS) whether they received chemotherapy alone or with trastuzumab (10-year rate 90.9% versus 80.0%,P=0.21), Edith A. Perez, MD, of the Mayo Clinic in Jacksonville, Fla., and colleagues found.
“The rest showed, as expected, significantly better recurrence-free survival with addition of trastuzumab (10-year rate 79.6% versus 64.3%, hazard ratio 0.49, P=0.0003), they reported here at the San Antonio Breast Cancer Symposium.”