SUMMARY:In children and adolescents with acute lymphoblastic leukemia (ALL), allogeneic stem cell transplantation is usually considered the treatment option, after failure of remission-induction therapy. In their review of over 44,000 cases of pediatric ALL in three continents, the authors noted that patients with B-cell ALL had better outcomes when treated with a second round of chemotherapy without a transplant. Patients with T-cell ALL however were noted to have a better outcome with transplantation. This review suggests that induction failure in patients with ALL does not automatically warrant transplantation. Schrappe M, Hunger SP, Pui C, et al. N Engl J Med 2012; 366:1371-1381
Month: May 2012
Continuous Lenalidomide Treatment for Newly Diagnosed Multiple Myeloma
SUMMARY: REVLIMID® (Lenalidomide) is an immunomodulatory agent with significant activity in patients with Multiple Myeloma, by virtue of its multiple mechanism of action. In this randomized, double blind, multicenter study, patients 65 years or older with newly diagnosed multiple myeloma, ineligible for transplantation, were randomized and the comparison was MPR followed by R (melphalan, prednisone and REVLIMID® followed by REVLIMID® maintenance) vs MPR or MP followed by placebo. There was a statistically significant prolongation in the progression free survival with a 51% reduction in the risk of progression for those who received REVLIMID® maintenance (MPR followed by R) compared to those who received MPR followed by placebo. This benefit was predominantly observed in patients who were 65-75 years of age. The response rates were also higher in the MPR-R and MPR groups compared to the MP group. There was a slightly higher incidence of second primary malignancies in those exposed to REVLIMID® (MPR-R and MPR) compared to the MP group (7% vs 3%). This study has demonstrated the benefit of adding REVLIMID® for induction therapy as well as maintenance, in patients 65-75 years of age, ineligible for transplant. Palumbo A, Hajek R, Delforge M, et al. N Engl J Med 2012;366:1759-1769
Lenalidomide after Stem-Cell Transplantation for Multiple Myeloma
SUMMARY: REVLIMID® (Lenalidomide) is an immunomodulatory agent with significant activity in patients with Multiple Myeloma, by virtue of its multiple mechanisms of action. In two, double blind, randomized, phase III trials, patients with stable disease following stem cell transplantation, were randomized to receive either REVLIMID® (Lenalidomide) or placebo maintenance, until progression. In both these studies there was a statistically significant improvement in the progression free survival or time to progression in the patient group receiving REVLIMID® maintenance. This benefit was independent of response to initial induction therapy at the time of randomization and other patient characteristics such as B2 microglobulin, cytogenetics or exposure to lenalidomide or thalidomide during induction. There was however a slightly higher incidence of second primary malignancies in the REVLIMID® group compared to the placebo group (8% vs 4%). We have come a long way, controlling this disease and maintenance REVLIMID® has paved the way, changing Multiple Myeloma into a chronic disease. McCarthy PL, Owzar K, Hofmeister CC, et al. N Engl J Med 2012;366:1770-1781 and Attal M, Lauwers-Cances V, Marit G, et al. N Engl J Med 2012;366:1782-1791
Everolimus in Postmenopausal Hormone-Receptor–Positive Advanced Breast Cancer
SUMMARY: The mechanism of resistance to hormonal therapy in breast cancer is thought to be related to the activation of mTOR pathway, independent of ER (estrogen receptor) signalling pathway. To test this hypothesis, the authors in this study (BOLERO-2) decided to combine mTOR inhibition with estrogen deprivation. In a phase III trial, patients with ER positive, advanced breast cancer, who had recurred or progressed on prior therapy with nonsteroidal aromatase inhibitors (anastrozole or letrazole), were randomized in a 2:1 ratio to either receive everolimus (mTOR inhibitor) and exemestane (steroidal aromatase inhibitor) or exemestane and placebo. The primary end point of Progression Free Survival was significant with 10.6 months for mTOR inhibitor plus exemestane vs 4.1 months for exemestane plus placebo, according to central review (hazard ratio, 0.36; P<0.001). This new paradigm of adding everolimus to hormonal therapy should change the way we manage patients with advanced breast cancer, who are resistant to hormonal therapy alone. Baselga J, Campone M, Piccart M, et al. N Engl J Med 2012; 366:520-529
Effect of MDV3100, an androgen receptor signaling inhibitor (ARSI), on overall survival in patients with prostate cancer post docetaxel Results from the phase III AFFIRM study
SUMMARY: MDV3100 is an androgen receptor antagonist with a significantly higher binding affinity for the androgen receptor (AR) compared to the antiandrogen bicalutamide and there by competitively inhibits the binding of androgens to the androgen receptor. Majority of the patients with advanced prostate cancer become refractory to hormone therapy because of increased production of androgen receptors by the tumors as well as mutated androgen receptors. The superiority of this novel agent, MDV3100, is based on the fact that the expression of androgen dependent genes are downregulated with MDV 3100 leading to cell death or apoptosis, whereas with bicalutamide the expression of these genes are upregulated. Further MDV3100 continues to antagonize mutated androgen receptors on the prostate tumor cells in contrast to bicalutamide which behaves as an agonist. It is thus an androgen receptor signaling inhibitor (ARSI). The AFFIRM clinical trial is a randomized, multinational phase III study in which patients who had received prior docetaxel-based chemotherapy regimens were randomized 2:1 to receive either MDV3100, 160 mg/day or placebo. Patients treated with MDV3100 had a median survival of 18.4 months, compared with 13.6 months for men treated with placebo, with a median OS advantage of 4.8 months and a reduction in the risk of death by 37%. Scher HI, Fizazi K, Saad F, et al. J Clin Oncol 30, 2012 (suppl 5; abstr LBA1)
Results of a phase III randomized, double-blind, placebo-controlled, multicenter trial (CORRECT) of regorafenib plus best supportive care (BSC) versus placebo plus BSC in patients (pts) with metastatic colorectal cancer (mCRC) who have progressed after standard therapies
SUMMARY: In this phase III trial, patients with metastatic colorectal carcinoma who had progressed after approved standard therapies were randomly assigned in a 2:1 ratio to receive either Regorafenib, an oral multikinase inhibitor plus best supportive care or placebo plus best supportive care. Seven hundred and sixty patients were randomized. Patients receiving Regorafenib had a statistically significant improvement in the overall survival and progression free survival compared to placebo, without any unexpected toxicities. This important study gives a new option for individuals with advanced colorectal cancer who have progressed on all available standard therapies. Grothey A, F. Sobrero AF, Siena S, et al. J Clin Oncol 30, 2012 (suppl 4; abstr LBA385)
Risk Factors for Breast Cancer for Women Aged 40 to 49 Years
SUMMARY: There is presently no clear consensus regarding breast cancer screening for women in their 40’s. The risk/benefit ratio of screening mammography has not been properly defined in this age group. In this review, Nelson and colleagues identified the risk factors for breast cancer and concluded that there is a 2 fold increase in the risk for breast cancer in women 40-49 years of age, who have dense breast tissue and first degree relatives with breast cancer. This meta analysis has identified a subset of patients in their 40’s who would benefit from screening mammography. Nelson HD, Zakher B, Cantor A, et al. Ann Intern Med. 2012;156:635-648
Bevacizumab (BEV) plus chemotherapy (CT) continued beyond first progression in patients with metastatic colorectal cancer (mCRC) previously treated with BEV plus CT Results of a randomized phase III intergroup study (TML study)
SUMMARY:The ML18147 (TML) is a randomized phase III trial in which patients who received AVASTIN® (Bevacizumab) plus standard chemotherapy as initial treatment (first-line treatment) for their metastatic colorectal cancer were then randomized to either continue AVASTIN® with a different chemotherapy after their cancer progressed (second-line treatment) or receive the different chemotherapy regimen without AVASTIN®. Patient group continuing AVASTIN® as a part of second line treatment demonstrated an improved survival compared to those who received chemotherapy alone, as second line treatment. This study has demonstrated that continuing AVASTIN® with second line chemotherapy post progression, extends survival in patients with metastatic colorectal cancer. Arnold D, Andre T, Bennouna J, et al. J Clin Oncol 30, 2012 (suppl; abstr CRA3503)