Kadcyla given after Chemotherapy Does Not Cause Cardiac Side Effects

“In a study reported in the Journal of Clinical Oncology, Krop et al found that ado-trastuzumab emtansine (Kadcyla) had an acceptable cardiac safety profile when used after anthracycline-based (neo)adjuvant therapy in women with early-stage HER2-positive breast cancer.

“In the study, 153 patients with a pretreatment left ventricular ejection fraction > 55% received (neo)adjuvant doxorubicin-cyclophosphamide for four cycles or fluorouracil, epirubicin, and cyclophosphamide for three or four cycles followed by ado-trastuzumab emtansine 3.6 mg/kg every 3 weeks for four cycles. Patients could then receive three or four cycles of docetaxel with or without trastuzumab (Herceptin). Ado-trastuzumab emtasine treatment was then resumed with optional sequential or concurrent radiotherapy for up to 1 year (17 cycles)…

“The investigators concluded: ‘Use of [ado-trastuzumab emtansine] for approximately 1 year after anthracycline-based chemotherapy was feasible and generally well tolerated by patients with HER2-positive [early-stage breast cancer], providing support for phase III trials of [ado-trastuzumab emtansine] in this setting.’ “


Genentech Distribution Shift for Cancer Meds Delays Patient Care: Survey

“A new survey of hospitals and academic medical centers finds that a recent move by Genentech to switch distribution of three widely used cancer treatments – Avastin, Rituxan and Herceptin – is resulting in higher costs, reduced access to the medications and delays in treating patients. And the institutions are hoping the results will prompt the drug maker, which says it’s unaware of such problems, to revert to its earlier distribution program.

“Here’s the background: Last fall, Genentech began using just a few distributors that specialize in handling such medicines. Until then, the Roche unit used dozens of wholesalers, although the specialty distributors are actually divisions of some of those same wholesalers. Genentech says the change was made to save money, but also make distribution more efficient and prevent the possibility of shortages.

“However, most of the institutions – 93% – say they had not experienced shortages, and the move has disrupted not only their finances, but patient care. The survey also found that 81% say the switch will have a moderate to significant impact on their expenses. Meanwhile, 63% say deliveries have been unreliable and 88% reported a delay in patient treatment because one of the drugs was unavailable.

“The institutions say they are forced to increase inventories to hedge against any supply disruptions that may occur because shipping can take longer, depending upon the location of the distributor. Some institutions say they cannot afford to keep large amounts of drug on hand, which can result in delays in treating new patients or unexpected events. And previous discounts may no longer be available.”


Combined Therapy Can Reduce Chance of Recurrence in Women with Small, HER2-Positive Breast Tumors

The gist: After surgery to remove their tumors, women with stage I, HER2-positive breast cancer might benefit from a combination of lower-intensity chemotherapy and the targeted drug trastuzumab (Herceptin). In a clinical trial, patients received post-surgery (adjuvant) treatment with the drugs paclitaxel and Herceptin. After three years, 98.7% were alive and had not experienced return of invasive breast cancer.

“In a phase 2 clinical trial, women with small (stage 1), HER2-positive breast tumors who received a combination of lower-intensity chemotherapy and a targeted drug following surgery were highly unlikely to have the cancer recur within three years of treatment, investigators at Dana-Farber Cancer Institute and other institutions report in a paper published today by the New England Journal of Medicine.

“The findings may help establish the therapy – which combines the agent paclitaxel and the targeted drug trastuzumab (Herceptin) – as the first standard treatment approach for this group of patients, the authors state.

” ‘Many previous studies excluded women with small (less than 2 cm in diameter) HER2-positive that hadn’t spread to nearby lymph nodes from clinical trials of trastuzumab, because it wasn’t considered prudent to expose them to an investigational drug, given the relatively low risk that the disease would recur. Without a single, standard treatment for this group of patients, treatment approaches have varied widely. (Breast cancers are classified as HER2-positive if their cells have surplus human epidermal growth factor receptors on their surface, making them extra-sensitive to signals to grow and divide.)”


PIK3CA Mutations Matter in HER2-Positive Breast Cancer

The gist: Recent research suggests that women whose tumors have a mutation in the PIK3CA gene may be resistant to treatment with the drugs trastuzumab (Herceptin) and lapatinib. However, two new studies say that PIK3CA mutations can’t be used to predict how well Herceptin and lapatinib will work.

“While preclinical studies indicate that PIK3CA mutations result in resistance to the two HER2-targeted therapies trastuzumab and lapatinib, two recently published studies suggest that this mutation cannot be used as a predictive biomarker to guide therapy.

“The first study found that PIK3CA mutations are associated with a decreased benefit to neoadjuvant HER2-directed therapies. The second study showed that PIK3CA mutations did not affect outcomes for HER2-positive patients receiving adjuvant trastuzumab treatment.

“Preclinical studies using HER2-positive cell lines have previously shown that an additional mutation in PIK3CA, the alpha-catalytic subunit of PI3K, results in downstream constitutive signaling, making breast tumor cells that harbor both aberrations resistant to trastuzumab and lapatinib. PIK3CA is among the most commonly mutated oncogene in breast cancer and is present in about one-fourth of all HER2-positive breast cancers. Because of this prevalence and the effect of PI3K pathway activation on HER2 therapy, clinicians have posited that PIK3CA mutations may serve as predictive biomarkers, both preventing ineffectual therapy in some patients and guiding appropriate treatment choices.”


Subcutaneous, IV Trastuzumab Similarly Safe, Effective for HER-2-Positive Early Breast Cancer

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.”


TDM-1 Trial Disappoints in HER2-Positive Breast Cancer

The gist: A clinical trial that tested a new drug called TDM-1 (Kadcyla) found disappointing results for patients with metastatic, HER2-positive breast cancer. The trial found that treatment with T-DM1 plus the drug pertuzumab is no better than treatment with trastuzumab plus chemotherapy. For more on TDM-1, see this recent news about its potential benefits for patients whose cancer has spread to the central nervous system (CNS).

“Results of the anticipated phase III MARIANNE trial found that HER2-positive metastatic breast cancer patients treated with trastuzumab emtansine (T-DM1) plus pertuzumab had similar progression-free survival (PFS) compared with those treated with trastuzumab plus a taxane-based chemotherapy.

“Though the trial met its noninferiority endpoint, showing a similar PFS in the first-line setting between the two combination therapies along with T-DM1 alone, it failed to demonstrate that T-DM1 performs better than trastuzumab plus chemotherapy.

“The study has been anticipated by clinicians as two of the treatment arms do not include a taxane, which often causes patients to lose their hair, among other toxicities. The full results of the study will be presented at a future medical meeting…

“ ‘In my opinion, given the substantial survival associated with [docetaxel plus trastuzumab and pertuzumab of over 56 months], it remains the current first-line standard regimen especially for those patients who have never been exposed to trastuzumab,’ said Hurvitz.”


Kadcyla/Perjeta Combo Does Not Improve Outcomes for Patients with Advanced, Untreated, HER2-Positive Breast Cancer

The gist: Combining the breast cancer drugs Kadcyla and Perjeta does not seem to improve outcomes for advanced, HER2-positive patients, compared to Kadcyla alone or Herceptin plus chemotherapy. That was the conclusion of a recent clinical trial that tested the combo in people who had not yet been treated for their advanced cancer. Herceptin plus chemotherapy is a cheaper option than Kadcyla plus Perjeta.

“Patients who got a combination of Kadcyla and Perjeta lived without their disease worsening for a similar amount of time as those who got Kadcyla alone, or those receiving the older medicine Herceptin plus chemotherapy, the Basel, Switzerland-based company said in a statement today. The study, dubbed Marianne, looked at 1,095 patients with a genetic mutation known as HER2 whose cancer has spread and who haven’t already tried other treatments.

“A successful combination of Kadcyla and Perjeta may have helped Roche replace sales of Herceptin that the company would lose should that medicine face competition from cheaper copies in coming years. Herceptin was Roche’s third-biggest drug in the first nine months of this year, with revenue of 4.7 billion Swiss francs ($4.8 billion).”


Drug Fails in Advanced HER2+ Breast Cancer

“Novartis’ drug Afinitor failed to significantly improve disease-free survival in women with a certain type of advanced breast cancer, a late-stage study presented at the San Antonio Breast Cancer Symposium on Friday showed.

“Results of the Phase III study involving 719 patients found women taking Afinitor in combination with Roche’s breast cancer drug Herceptin and chemotherapy agent paclitaxel lived on average for 15 months without their disease worsening.

“This compared with 14.5 months for those on placebo, the Swiss drugmaker said.

“The study was evaluating the drug as a treatment for women with advanced HER2-positive breast cancer, which is responsible for approximately 20 percent of breast cancer diagnoses.

“Afinitor is already approved in the European Union as a treatment for HER2-negative advanced breast cancer. (Reporting by Caroline Copley)”


Longer Neoadjuvant Anti-HER2 Treatment Might Be More Effective for HER2+ Patients

The gist: Stage II and III breast cancer patients whose tumors are HER2-positive may benefit from longer treatment with the anti-HER2 drugs trastuzumab (aka Herceptin) and lapatinib (Tykerb). In a clinical trial, 28% of patients who received the drugs for 24 weeks had no more signs of an invasive tumor after their treatment. Only 12% of patients who received the drugs for 12 weeks had the same result. However, the difference in response was significant only in patients whose tumors were hormone receptor (HR)-positive and HER2-positive.