“A new randomized trial found that neoadjuvant trastuzumab/pertuzumab alone yields a substantially worse rate of pathologic complete response compared with trastuzumab/pertuzumab plus paclitaxel in women with early, HER2-positive, hormone receptor (HR)-negative breast cancer.
” ‘Pathologic complete response (pCR) after neoadjuvant [therapy] has strong prognostic impact in HER2 disease,’ wrote study authors led by Ulrike Nitz, MD, of the West German Study Group GmbH in Moenchengladbach, Germany. The WSG-ADAPT HER2+/HR− trial assessed whether dual blockade with trastuzumab and pertuzumab could achieve similar rates of pCR in those with strong early response to dual blockade along with chemotherapy.”
Non-metastatic breast cancers are most often treated with surgery, but if the tumors are fairly large, or involve nearby lymph nodes, neoadjuvant (pre-operative) treatments with chemotherapy (NAC) are done first. NAC often reduces the tumor size and kills cancer cells in lymph nodes, if present, prior to surgery, improving the outcome. The best possible result of neoadjuvant treatment is pCR (pathologic compete response), when the tumor is no longer visible in imaging studies. Here, I review the new directions in which neoadjuvant treatments are evolving.
Today, treatments for metastatic breast cancers are tailored for specific subtypes. Starting with the introduction of the drug trastuzumab (Herceptin) for HER2-positive cancers, new, more specific treatment options were eventually developed and approved for other types as well. Estrogen deprivation endocrine therapies, lately prescribed in combination with CDK4/6 inhibitors, are used in estrogen receptor (ER)-positive cancers. Triple negative cancers (TNBC) are still treated mostly with chemotherapy, but immune checkpoint drugs and PARP inhibitors are explored in clinical trials, with some successes reported.
However, neoadjuvant treatments (except for HER2+ cancers) remain largely limited to chemotherapy regimens. This is starting to change now, with new approaches tailored to the cancer type being investigated in clinical trials.
In this regard, it is important to mention the I-SPY2 trial, NCT01042379, which started in 2010 and is for women with stage II-III breast cancer. It offers about a dozen drugs that are chosen based on particular features of the newly diagnosed cancers. This trial has a unique design and has produced some important results. Additional treatments and trials for various types of breast cancer are discussed below. Continue reading…
“Twelve weeks of neoadjuvant T-DM1 (ado-trastuzumab emtansine; Kadcyla) with or without endocrine therapy induced superior pathologic complete response (pCR) compared with trastuzumab (Herceptin) plus endocrine therapy in patients with HER2-positive/HR-positive early breast cancer, according to findings recently published online in theJournal of Clinical Oncology.
“In the prospective, neoadjuvant phase II ADAPT trial conducted by the West German Study Group, pCR was 41.0% for patients assigned to T-DM1 alone and 41.5% for those who received T-DM1 and endocrine therapy. In contrast, 15.1% of patients assigned to trastuzumab and endocrine therapy had a pCR (P<.001).”
“The U.S. Food and Drug Administration today approved Nerlynx (neratinib) for the extended adjuvant treatment of early-stage, HER2-positive breast cancer. For patients with this type of cancer, Nerlynx is the first extended adjuvant therapy, a form of therapy that is taken after an initial treatment to further lower the risk of the cancer coming back. Nerlynx is indicated for adult patients who have been previously treated with a regimen that includes the drug trastuzumab.”
“The triplet combination of HER2-targeted therapy and an aromatase inhibitor (AI) improved progression-free survival (PFS) by more than 5 months compared with the combination of trastuzumab (Herceptin) and an AI in patients with HER2+/HR+ breast cancer.
“In phase III results from the ALTERNATIVE trial presented at the 2017 ASCO Annual Meeting, the median PFS was 11 months (95% CI, 8.3-13.8) for postmenopausal women with HER2+/HR+ metastatic breast cancer assigned to lapatinib (Tykerb) plus trastuzumab plus an AI compared with 5.7 months (95% CI, 5.5-8.4) for patients assigned to trastuzumab plus an AI. Lead study author William J. Gradishar MD, interim chief of hematology and oncology at Northwestern University’s Feinberg School of Medicine, said that represented a 38% reduction in the risk of progression (HR, 0.62; 95% CI, 0.45-0.88; P = .0064).”
Last month, the annual American Society of Clinical Oncology (ASCO) meeting took place in Chicago. Thousands of oncologists, patients, and journalists gathered to learn about the most recent developments in cancer research and treatment. Here are some breast cancer highlights from the meeting:
Triple negative breast cancer (TNBC) is considered more responsive to treatment with immune checkpoint drugs than any other type of breast cancer. So far, these drugs have primarily been explored in metastatic TNBC, in combination with chemotherapy. The combination of “anti-PD-L1” and “anti-PD-1” immune checkpoint drugs with chemotherapy has now been examined in early-stage TNBC, in which a breast tumor can be surgically removed after neoadjuvant chemotherapy. Continue reading…
“Dual blockade of HER2 with lapatinib plus trastuzumab and an aromatase inhibitor (AI) was superior to single blockade with trastuzumab plus an AI in postmenopausal women with HER2-positive, hormone receptor (HR)-positive metastatic breast cancer, according to the results of the phase III ALTERNATIVE study (abstract 1004) presented at the 2017 American Society of Clinical Oncology (ASCO) Annual Meeting, held June 2–6 in Chicago.
” ‘Dual HER2 blockade with this triplet of lapatinib/trastuzumab and an AI can offer an effective and well-tolerated chemotherapy-sparing option for patients who are not intended or appropriate for chemotherapy,’ said researcher William J. Gradishar, MD, of the Robert H. Lurie Comprehensive Cancer Center at Northwestern University in Chicago, who presented the results.”
“Another potential drug for HER2-positive breast cancer received strong numeric support from an FDA advisory committee, tempered by reservations about a broad indication, modest clinical benefit, and toxicity issues.
“By a 12-4 vote, the Oncologic Drugs Advisory Committee (ODAC) supported FDA approval of the dual HER2/EGFR inhibitor neratinib for early HER2-positive breast cancer that relapses after trastuzumab (Herceptin) maintenance therapy.”
“A cost-effectiveness analysis found that 9 weeks of trastuzumab therapy is better than the more standard 12 months in patients with HER2-positive breast cancer, without loss of clinical efficacy. The analysis is limited, though, by the need to combine various trials rather than any head-to-head comparisons.
“Trastuzumab has been shown to significantly improve survival in women with HER2-positive disease. ‘The budget impact of trastuzumab is high, mostly due to the drug’s high cost, and the most serious adverse effect observed is cardiac dysfunction,’ wrote study authors led by Caroline Clarke, PhD, of University College London in the United Kingdom. Though 12 months is considered the standard duration of therapy, some studies have also found similar results with only 9 or 10 weeks of trastuzumab.”