SUMMARY: The TROPIC trial (Treatment of Hormone-Refractory Metastatic Prostate Cancer Previously Treated With a docetaxel (TAXOTERE®)- Containing Regimen) involved 755 men in 26 countries with metastatic prostate cancer who were castration resistant. Patients were randomized to receive either Cabazitaxel (JEVTANA®) 25 mg/m2 or Mitoxantrone 12 mg/m2 three times a week and both groups received prednisone 10 mg daily through out the course of their treatment. The combination of JEVTANA® and prednisone resulted in median overall survival of 15.1 months compared to 12.7 months for the Mitoxantrone group. There was a 30% reduction in the risk of death for the JEVTANA® group. This led to the approval of JEVTANA® for the treatment of hormone-refractory metastatic prostate cancer, previously treated with a TAXOTERE® containing regimen. Lancet 2010;376:1147-1154
Category: Hem/Onc Updates
A phase III study (EMBRACE) of eribulin mesylate versus treatment of physician’s choice in patients with locally recurrent or metastatic breast cancer previously treated with an anthracycline and a taxane
SUMMARY: HALAVEN ® (Eribulin) is a non taxane inhibitor of microtubule dynamics and is a synthetic analog of halichondrin B, a product derived from a a sea sponge Halichodria okadai. It triggers apoptosis of cancer cells following prolonged mitotic inhibition. The EMBRACE trial is a randomized open label phase III study involving 762 heavily pretreated patients with locally recurrent or metastatic breast cancer. These patients must have had at least two prior chemotherapy regimens including taxanes and an anthracycline. Patients were randomized to either HALAVEN ® (508 patients) or to an approved treatment of their physician's choice and this could be single agent chemotherapy, hormonal therapy, biological therapy or palliative radiation therapy (254 patients). Nineteen percent of the patients had triple negative disease. There was a statistically significant improvement in overall survival in the HALAVEN ® group 13.1 months compared to 10.7 months in the control group. At one year, 54% of the patients were alive in the HALAVEN ® group compared to 44% in the control group. This statistically significant benefit was also seen in the overall response rates. We now have another agent with a distinct survival advantage for heavily pretreated metastatic breast cancer patients. J Clin Oncol 28:18s, 2010 (suppl; abstr CRA1004)
Sipuleucel-T Immunotherapy for Castration-Resistant Prostate Cancer
SUMMARY: Sipuleucel-T (PROVENGE®) is a therapeutic cancer vaccine developed to boost the patients immune system to fight prostate cancer. In a double blind randomized phase III trial, 512 patients with metastatic castrate-resistant prostate cancer received PROVENGE® vaccine (341) or a placebo (171). There was a 4.1 month improvement in median survival for patients receiving the vaccine compared to those receiving a placebo (25.8 versus 21.7 months) and a 22% reduction in the risk of death in the vaccine group. Because of the slow onset of action of any vaccine therapy, this option may be appropriate for individuals with less aggressive disease. N Engl J Med 2010;363:411-422
Results of a randomized, phase III trial of nab-paclitaxel (nab-P) and carboplatin (C) compared with cremophor-based paclitaxel (P) and carboplatin as first-line therapy in advanced non-small cell lung cancer (NSCLC)
SUMMARY: In this randomized phase III trial, the efficacy of nab-paclitaxel (ABRAXANE®) and carboplatin was compared with paclitaxel and carboplatin in advanced NSCLC of all histologic types. Patients enrolled were chemonaïve, with stage IIIb and stage IV non small cell lung cancer. Five hundred and twenty one (521) received ABRAXANE® without any premedications at 100 mg/m2 on days 1, 8 and 15 along with carboplatin given on day 1 at an AUC of 6. The control group of 525 patients received standard Paclitaxel 200mg/m2 and carboplatin at an AUC of 6 on day 1. The primary end point was overall response rate. The ABRAXANE® group had a response rate of 33% compared to 25% for the standard paclitaxel group. When broken down by histology, the response rates in those with squamous cell carcinoma was 41% in the ABRAXANE® group versus 24% in the standard paclitaxel arm and the non squamous subtypes had a response rate of 26% versus 25% in the ABRAXANE® and paclitaxel group respectively. It is hypothesized that the superior response rates in squamous cell histology may be due to the overexpression by this sub type of an albumin receptor called Caveolin–1. ABRAXANE® which is an albumin bound paclitaxel utilizes the albumin receptor Caveolin-1 (CAV1) pathway and thereby may achieve a higher intratumoral drug concentration. J Clin Oncol 28:18s, 2010 (suppl; abstr LBA7511)
New Biomarker to predict Cancer Recurrence or Metastasis
A protein variant of carboxypeptidase E has now been shown to induce tumor growth and metastases. By measuring the level of this protein in the tumor and surrounding tissue, we may soon be able to predict whether a tumor is likely to spread or has already spread. The predictability of tumor behavior, using this new novel biomarker, appears to trump the outcomes based on staging and grade of the tumor. The tempo of the disease even in patients with advanced cancer can be predicted measuring the levels of this biomarker, with tumors expressing high levels of this protein doing poorly. This may also help the clinician determine when to treat a patient with cancer and when to just monitor without pursuing aggressive chemotherapeutic intervention.
These findings were published in the Journal of Clinical Investigation, Feb 2011.
Environment and Cancer
More than a third of Americans will develop some form of cancer during their life time. Interestingly 80-90% of the cancers in the western hemisphere has been attributed to environmental factors. With cancer being the second common cause of mortality in the USA, prevention of cancer related morbidity and mortality can be accomplished by avoiding environmental pollution with carcinogens and eliminating exposure to existing carcinogenic agents in the environment. This sentiment was eloquently verbalized by Dr. David Christiani in the March 3, 2011 issue of the NEJM.
Despite the progress made in cancer treatment and Genomics, we cannot lose sight of the fact that prevention is better than cure.
Breast Cancer – More is not necessarily better
It used to be that patients with breast cancer requiring surgery had Radical Mastectomy until the 1970’s. It subsequently became clear that Modified Radical Mastectomy, a less aggressive surgical procedure was just as effective as Radical Mastectomy. The next major surgical advance in Breast Cancer was breast preservation with Lumpectomy, Axillary Lymph Node Dissection (ALND) and Radiation. This has been proven to be as good as Modified Radical Mastectomy. Because of the morbidity associated with complete ALND, the technique of Sentinel Lymph Node Dissection (SLND) was developed and it became clear that SLND by itself is as effective as ALND, in early breast cancer, without the complications associated with ALND.
A randomized clinical trial results published in JAMA this month demonstrated that in women with invasive breast cancer and limited sentinel lymph node metastases, SLND was as effective as ALND. With this data, women diagnosed with breast cancer hopefully will not have to endure the morbidity associated with ALND which include swelling, pain, paresthesias and restriction of movement of the arm.
This philosophy of ” more is not better” with regards to chemotherapy, held ground, after myeloablative therapy and transplantation for metastatic breast cancer patients showed no benefit. Hopefully newer “kinder and gentler” systemic agents will follow suit, just as the surgical techniques have evolved over the past 40 years.
Maintenance Rituximab
The FDA on Jan 31, 2011 approved Rituximab as a maintenance treatment for patients with advanced follicular lymphoma, who responded to initial treatment with Rituximab plus chemotherapy. Follicular lymphomas are a subset of Non Hodgkins Lymphomas and are very responsive to chemotherapy or chemotherapy with Rituximab. They are usually incurable however, despite treatment with Rituximab plus chemotherapy. So think of this condition as a chronic disease. For this reason, prolonging remission duration is important, as the length of remission tends to be shorter with each recurrence.
In the PRIMA trial, which was a phase III study, maintenance Rituximab for 2 years given to those who responded to induction treatment with chemotherapy and Rituximab, delayed the risk of recurrence and improved progression free survival. These findings are relevant for patients who essentially have a chronic disease and are willing to pursue interventions that would delay recurrence of their lymphoma and therefore improve their quality of lives.
PARP Inhibition in Triple Negative Breast Cancer
Patients with triple negative breast cancer have inherent defects in several DNA repair pathways. These cancer cells therefore become increasing dependent on another DNA damage repair pathway called base excision repair (BER) pathway, for survival. It so happens that PARP 1(PolyAdenosine diphosphate Ribose Polymerase) is an important enzyme regulating the BER pathway. By inhibiting PARP1, the BER pathway is inhibited leading to extreme levels of DNA damage and eventual death of cancer cells.
In an article published in the Jan 20,2011 issue of the NEJM, the addition of a PARP inhibitor Iniparib to a combination of Carboplatin and Gemzar in patients with metastatic triple negative breast cancer, resulted in superior Response Rates, median Progression Free Survival and Overall Survival. This difficult -to -treat subtype of breast cancer may soon become extinct.
Improving Survival in Metastatic Pancreatic Cancer
A combination of Oxaliplatin, Irinotecan, Fluorouracil and Leucovorin (FOLFIRINOX) chemotherapy given to individuals with metastatic pancreatic cancer resulted in superior Response Rates, Progression Free Survival and Overall Survival compared to single agent Gemcitabine. For the first time, we now have a regimen that has demonstrated survival benefit for this hard-to-treat cancer.
This data was presented at the 2010 ASCO meeting