Everolimus–Exemestane Combination Failed to Significantly Extend OS in Advanced Breast Cancer

The gist: A clinical trial with volunteer patients tested a treatment for postmenopausal women with HR-positive, HER-2–negative advanced breast cancer. The treatment combines the drugs everolimus and exemestane. The clinical trial compared it to exemestane alone. The combination did NOT appear to give longer overall survival rates than exemestane alone.

“The addition of everolimus to exemestane extended OS in postmenopausal women with HR-positive, HER-2–negative advanced breast cancer, but the difference was not statistically significant, according to results of the BOLERO-2 study.

“BOLERO-2 is a randomized phase 3, double blind, international trial.

“Prior results showed the addition of 10 mg daily everolimus (Afinitor, Novartis) — an inhibitor of mammalian target of rapamycin (mTOR) — to 25 mg daily exemestane significantly extended PFS compared with exemestane alone (7.8 months vs. 3.2 months; P<.001).

“In the current study, Martine Piccart, MD, PhD, professor of oncology at the Université Libre de Bruxelles in Belgium and director of medicine at Institut Jules Bordet, and colleagues presented OS outcomes as part of a prospectively planned secondary-endpoint analysis.

“Results showed patients assigned the combination demonstrated longer median OS (31 months vs. 26.6 months; HR=0.89; 95% CI, 0.73-1.1), but the difference was not statistically significant.

“ ‘Ongoing translational research should further refine the benefit of mTOR inhibition and related pathways in this treatment setting,’ Piccart and colleagues wrote.”


Everolimus Plus Exemestane Extended PFS in Invasive Lobular Carcinoma

The gist: This article discusses the results of a clinical trial—a research study with volunteer patients. The trial tested a new treatment for patients with advanced, HR-positive, HER-2-negative invasive lobular carcinoma. The new treatment combines the drugs everolimus and exemestane. The researchers found that it significantly prolonged the amount of time patients lived without their cancer worsening.

“The addition of everolimus to exemestane significantly prolonged PFS in a subset of patients with HR-positive, HER-2–negative advanced breast cancer who had invasive lobular carcinoma at baseline, according to a subanalysis of the BOLERO-2 trial presented at the Breast Cancer Symposium.

“Gabriel N. Hortobagyi, MD, FACP, professor of medicine in the department of breast medical oncology at The University of Texas MD Anderson Cancer Center, and colleagues evaluated data from 104 patients with invasive lobular carcinoma. The cohort included patients with predominantly peritoneal, gastrointestinal and ovarian metastases.

“Patients received exemestane (Aromasin, Pfizer) with everolimus (Afinitor, Novartis; n=64) or placebo (n=40).

“The median age of the patients was 63 years, and 47.1% had measurable disease. Thirty-six percent of patients had visceral metastases of the lung, liver, pleural and peritoneum; 10% had lung metastases; and 23% had liver metastases.”


Lpath Reports Interim Data From Phase 2a Study for Anti-Cancer Drug, ASONEP

Editor’s note: Researchers are conducting a clinical trial with volunteer patients to test a new kidney cancer treatment called ASONEP. Specifically, the trial is testing the effectiveness of ASONEP for people with metastatic renal cell carcinoma (RCC) who were previously but unsuccessfully treated with at least one “VEGF inhibitor” drug (like Sutent, aka sunitinib) and no more than one “mTOR inhibitor” drug (like Afinitor, aka everolimus), with a maximum of three unsuccessful previous treatments overall. The clinical trial is ongoing, but interim results show that ASONEP is safe and hasn’t caused serious side effects. The researchers also said the drug appeared to show promise as a cancer-fighting treatment.

“Lpath, Inc. (NASDAQ: LPTN), the industry leader in bioactive lipid-targeted therapeutics, reported interim results in a Phase 2a single-arm, open-label trial where ASONEP™ is being investigated as a treatment for metastatic renal cell carcinoma (RCC) in patients that have failed at least one therapy involving a VEGF inhibitor (e.g., Sutent®/ sunitinib maleate) and no more than one mTOR inhibitor (e.g., Afinitor®/everolimus), with a maximum of three failed treatments in all. This patient population is considered “last line,” and the literature suggests cancer progression in this population within a one-to-two month time frame.

“Lpath has enrolled 26 patients in the study. ASONEP has a favorable safety profile thus far, with no serious adverse events (SAEs) deemed to be drug-related.

“The first 17 patients were initiated at a dose of 15 mg/kg. Of these “lower-dose” patients:  7 had progressive disease at or before the end of four months; 8 were progression-free at the four-month mark (with 1 of these patients deemed a partial responder per Response Evaluation Criteria in Solid Tumors (RECIST) criteria and with 3 of these patients experiencing reduced tumor volume, but not enough to be categorized as a RECIST-based partial responder); and 2 exited the study due to SAEs unrelated to the drug prior to the four-month mark (and are not considered evaluable). Notably, of the 8 patients that were stable or better as of month four, 2 are now in their fifteenth month on the study, 1 is in month thirteen, and 1 is in month ten. An additional patient was stable through month seven, but then missed six treatments during a vacation, and shortly thereafter progressed.”


Lung Cancer Drug Retaspimycin Fails Clinical Trial

A phase II clinical trial found no survival benefit for the lung cancer drug retaspimycin in non-small cell lung cancer (NSCLC). The trial examined NSCLC patients with a history of smoking who were given the chemotherapy agent docetaxel (Taxotere) either with or without retaspimycin. Adding retaspimycin did not improve overall survival in NSCLC patients in general or in the subset of patients with squamous cell carcinoma (a type of NSCLC closely linked to smoking). The company will complete enrollment in a separate study investigating retaspimycin in combination with everolimus (Afinitor) by the end of 2013, but will begin no further clinical trials with retaspimycin.


'Super Responders' May Hold Clues for Cancer Treatment

In rare, previously unexplained cases, individual cancer patients respond to treatment much better than others do. Now, faster and cheaper DNA sequencing is allowing researchers to search the entire genetic material of such patients for the causes of their ‘super responder’ status. In one case, researchers linked one patient’s exceptional response to Afinitor (everolimus) to a mutation in the TSC1 gene. They plan to develop a test for this mutation, hoping to identify other cancer patients who will respond strongly to Afinitor. Such studies may resurrect drug candidates that were abandoned after clinical trials, where they were ineffective in most, but very effective in a few patients. Clinical trials and clinics focusing specifically on super responders are being planned.


mTOR Inhibitors May Be Associated with Kidney Injury

A class of cancer drugs called mTOR inhibitors may produce kidney toxicity in at least some patients. mTOR inhibitors, including rapamycin (sirolimus/Rapamune), temsirolimus (Torisel), everolimus (Afinitor), and ridaforolimus, are used to treat certain forms of breast and kidney cancer, and are under investigation for several other cancers. Researchers described four cases of patients treated with mTOR inhibitors developing severe acute kidney injury. They recommend that doctors carefully monitor kidney function in patients receiving these drugs. However, other experts emphasize that it is unclear whether the mTOR inhibitors were indeed the cause of the kidney injury. In at least one case, the patient was also taking other drugs known to cause kidney toxicity.


mTOR Inhibitors May Be Associated with Kidney Injury

A class of cancer drugs called mTOR inhibitors may produce kidney toxicity in at least some patients. mTOR inhibitors, including rapamycin (sirolimus/Rapamune), temsirolimus (Torisel), everolimus (Afinitor), and ridaforolimus, are used to treat certain forms of breast and kidney cancer, and are under investigation for several other cancers. Researchers described four cases of patients treated with mTOR inhibitors developing severe acute kidney injury. They recommend that doctors carefully monitor kidney function in patients receiving these drugs. However, other experts emphasize that it is unclear whether the mTOR inhibitors were indeed the cause of the kidney injury. In at least one case, the patient was also taking other drugs known to cause kidney toxicity.


mTOR Inhibitors May Be Associated with Kidney Injury

A class of cancer drugs called mTOR inhibitors may produce kidney toxicity in at least some patients. mTOR inhibitors, including rapamycin (sirolimus/Rapamune), temsirolimus (Torisel), everolimus (Afinitor), and ridaforolimus, are used to treat certain forms of breast and kidney cancer, and are under investigation for several other cancers. Researchers described four cases of patients treated with mTOR inhibitors developing severe acute kidney injury. They recommend that doctors carefully monitor kidney function in patients receiving these drugs. However, other experts emphasize that it is unclear whether the mTOR inhibitors were indeed the cause of the kidney injury. In at least one case, the patient was also taking other drugs known to cause kidney toxicity.


Tarceva May Be More Effective in Advanced NSCLC When Combined with Other Targeted Therapies

An analysis of multiple clinical trials compared erlotinib (Tarceva) alone to combining Tarceva with other targeted therapies as second-line treatment for advanced non-small cell lung cancer (NSCLC). In the various trials, Tarceva was combined with bevacizumab (Avastin), bortezomib (Velcade), everolismus (Afinitor), sorafenib (Nexavar), sunitinib (Sutent), entinostat, tivantinib, and R1507. While combined therapy produced more side effects, it was more effective than Tarceva alone. Notably, the trials included many patients who had not been tested for mutations in the EGFR and KRAS genes. In patients who had EGFR mutations and/or lacked KRAS mutations, Tarceva alone tended to control cancer progression better than combined therapy, highlighting the importance of biomarker testing to identify which patients are most likely to benefit from different therapies.