Neoadjuvant Chemotherapy Plus Two Anti-HER2 Agents Optimal for HER2-Positive Breast Cancer

The gist: Before surgery to remove a tumor, breast cancer patients might take neoadjuvant therapy to shrink the tumor or otherwise help ensure a more successful surgery. A recent study concludes that combining two HER2-targeted drugs with chemotherapy might be the best neoadjuvant treatment choice for women with HER2-positive breast cancer. The researchers compared data from patients who received different combinations of chemotherapy, trastuzumab (Herceptin), and lapatinib (Tykerb). Patients who received all three had the highest chance of having no more signs of an invasive tumor after the treatment.

“For women with human epidermal growth factor receptor 2 (HER2)-positive breast cancer, combining two anti-HER2 agents with chemotherapy is the most effective treatment modality in the neoadjuvant setting, according to a meta-analysis published in the Journal of the National Cancer Institute.

“The study by Nagayama et al found that chemotherapy with trastuzumab (Herceptin) plus lapatinib (Tykerb), or with trastuzumab plus pertuzumab (Perjeta), resulted in a statistically significantly larger number of patients achieving pathologic complete response than did chemotherapy alone, chemotherapy with a single targeted therapy, or two anti-HER agents without chemotherapy. Ranking of treatment arms indicated that chemotherapy with trastuzumab plus pertuzumab “had the highest probability of being the best treatment arm in terms of [pathologic complete response],” the investigators stated.

“ ‘The growing number of HER2-targeted agents has created the need to define the optimal neoadjuvant therapy for HER2-positive breast cancer,’ the researchers wrote in explaining the rationale for the study. While other trials have been conducted to compare treatments, ‘it is difficult to integrate information on the relative efficacy of all tested regimens, since each trial has compared only a few treatments,’ the investigators noted.”


PIK3CA Mutation May Reduce Efficacy of Anti-HER2 Treatments

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.

“Newly diagnosed patients with HER2-positive breast cancer with tumors that harbor a PIK3CA mutation are not as likely to have a pathologic complete response (pCR) following HER2-targeted therapy plus neoadjuvant chemotherapy. This was the case regardless of whether patients were treated with single or combination HER2-targeted therapy. pCR rates were lowest for those patients with hormone receptor (HR)-positive, HER2-positive disease who harbored a PIK3CA mutation.

“This mutation may be a negative prognostic biomarker for HER2-positive patients. The study was published in the Journal of Clinical Oncology.

“According to the authors, this is the largest study to assess the link between PIK3CA mutations and pCR in HER2-positive disease.

“Only about one-third of women with HER2-positive breast cancer respond to anti-HER2 therapy—a treatment that has side effects and is costly. Still, all of these patients are ultimately treated with the same regimens because there are currently no assays that test whether a patient is likely to have an improved disease-free or overall survival from the therapy.”


Breast Cancer Specialist Reports Advance in Treatment of Triple-Negative Breast Cancer

“Because of its rapid growth rate, many women with triple-negative breast cancer receive chemotherapy to try to shrink it before undergoing surgery. With the standard treatment, the cancer is eliminated from the breast and lymph nodes in the armpit before surgery in about one third of women. This is referred to as a pathologic complete response (pCR). In patients who achieve pCR, the cancer is much less likely to come back, spread to other parts of the body, and cause the patient’s death than if the cancer survives the chemotherapy.

“Sikov and his collaborators studied the addition of other drugs – carboplatin and/or bevacizumab – to the standard treatment regimen to see if they could increase response rates. More than 440 women from cancer centers across the country enrolled in this randomized clinical trial.

” ‘Adding either of these medications significantly increased the percentage of women who achieved a pCR with the preoperative treatment. We hope that this means fewer women will relapse and die of their cancer, though the study is not large enough to prove this conclusively. Of the two agents we studied, we are more encouraged by the results from the addition of carboplatin, since it was associated with fewer and less concerning additional side effects than bevacizumab,’ Sikov explains.”

Editor’s note: This article describes the results of a clinical trial—a research study with volunteer patients.


Neoadjuvant Chemotherapy Reduces Postoperative Morbidity in Women With Breast Cancer Undergoing Mastectomy

Editor’s note: Cancer patients sometimes take neoadjuvant therapy—a treatment given before the main treatment to reduce the risk of the cancer returning later (recurrence). In a recent study, researchers looked at the effects of neoadjuvant chemotherapy for breast cancer patients before mastectomy. They measured morbidity, which they defined as a list of various conditions including surgical site infection, pneumonia, and sepsis. The researchers found that neoadjuvant chemotherapy reduced the risk of these conditions.

“In a study reported in JAMA Surgery, Abt et al found that neoadjuvant chemotherapy is safe in women with breast cancer undergoing mastectomy with or without immediate breast reconstruction. Neoadjuvant chemotherapy was an independent predictor of reduced 30-day postoperative morbidity in women undergoing mastectomy without breast reconstruction and in those undergoing immediate tissue expander breast reconstruction…

“The study included women in the American College of Surgeons National Surgical Quality Improvement Program database undergoing mastectomy with or without immediate breast reconstruction from January 2005 through December 2011. Rates of 30-day overall, systemic, and surgical postoperative morbidity were compared between women who did and did not receive neoadjuvant chemotherapy.

“Postoperative morbidity was defined as superficial and deep incisional surgical site infection, organ space surgical site infection, wound dehiscence, pneumonia, unplanned intubation, pulmonary embolism, > 48 hours of ventilatory assistance, progressive renal insufficiency, acute renal failure, urinary tract infection, stroke or cerebrovascular accident, coma > 24 hours, cardiac arrest, myocardial infarction, bleeding requiring transfusion, prosthesis or flap failure, deep vein thrombosis requiring treatment, sepsis, septic shock, and return to the operating room within 30 days.”


ASCO: Chemotherapy Key Part of Curative Lung Cancer Therapies

“Cancer Network: Thank you for speaking with us today, Dr. Kris. First, can you tell us why this is an important topic for an education session? Is there a debate of the use of chemotherapy in treating lung cancer?

“Dr. Kris: I wouldn’t quite say that there is a debate, but there is an impression that the therapy of lung cancers has switched to targeted therapies or immune therapies. Looking at the ASCO abstracts this year that would be an easy conclusion to draw. But there is an indisputable fact that no matter what target you can identify in a patient’s tumor, be it PD-L1 or a BRAF mutation, at some point in a patient’s illness they will be receiving chemotherapy. As we look at entire care of people with lung cancer it is very important to remember that virtually every single one will receive chemotherapy, and that we need to pay attention to choosing the best chemotherapy. We also need to think about doing research in chemotherapy. Clearly, we can do a better job, and we need more research to find the best drugs. Also, we need to find a way to use them with our targeted therapies.”

Editor’s note: Targeted therapies and immunotherapies are all the rage now in cancer treatment. But there are still important roles for chemotherapy. This article gives a great overview of recent advancements in the use of chemotherapy in lung cancer treatment, and why we need further research to refine and improve the benefits of chemotherapy.


Neoadjuvant Chemotherapy Reduced Mortality in Upper Tract Urothelial Carcinoma

“Neoadjuvant chemotherapy following surgery extended 5-year survival rates in patients with urothelial carcinoma, according to results of a retrospective study.

“Researchers reported a 5-year survival rate of 80.2% among patients who received neoadjuvant chemotherapy vs. 57.6% for patients who underwent surgery without chemotherapy.”

Editor’s note: Neoadjuvant treatment is a first-step treatment given to shrink a tumor before surgery to remove it. Neoadjuvant treatment can be performed with a variety of methods, including radiation therapy and hormone therapy. In this case, chemotherapy was used as a neoadjuvant, and appeared to benefit patients.

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Meta-Analysis Shows Survival Benefit of Preoperative Chemotherapy in NSCLC

“In a systematic review and individual patient meta-analysis reported in The Lancet, the NSCLC Meta-analysis Collaborative Group found that neoadjuvant therapy for non–small cell lung cancer (NSCLC) was associated with a significant 13% reduction in risk of death. Significant benefits in recurrence-free survival and time to distant recurrence were also observed…

“Preoperative chemotherapy was associated with a 13% improvement in overall survival.

“Preoperative chemotherapy was associated with a 15% improvement in recurrence-free survival and a 31% improvement in time to distant recurrence.”

Editor’s Note: “neoadjuvant therapy” refers to chemotherapy given before tumor removal surgery in the hopes of improving the success of the surgery.


Radiation and Chemotherapy before Surgery Best Option in Patients with Stage IIIA(N2) NSCLC

Disagreement persists about the best treatment for non-small cell lung cancer (NSCLC) patients with stage IIIA(N2) disease, that is, cancer that has spread to lymph nodes just outside the lung. A recent study compared the outcomes of different treatments. Patients who had received neoadjuvant chemoradiotherapy (chemotherapy and radiation administered before surgery) followed by lobectomy (removal of the lung subsection containing the cancer) had higher 5-year survival rates than patients treated with:

-neoadjuvant chemoradiotherapy and pneumonectomy (removal of the whole lung containing the cancer);

-either lobectomy or pneumonectomy plus adjuvant therapy (chemotherapy and/or radiation administered after surgery);

-concurrent chemoradiotherapy (chemotherapy and radiation delivered at the same time, without surgery).

These findings suggest that neoadjuvant chemoradiotherapy followed by lobectomy is the preferable treatment for stage IIIA(N2) NSCLC.