Improved Overall Survival In Patients Research Articles

Longer Duration of Treatment and Maintenance of Best Response with Lenalidomide and Dexamethasone Prolongs Overall Survival in Patients with Relapsed or Refractory Multiple Myeloma

Introduction: Multiple myeloma (MM) accounts for about 20% of deaths from hematological cancers and remains incurable despite conventional and high-dose chemotherapy. Two phase III trials in patients with relapsed or refractory MM (MM-009 and MM-010) showed that lenalidomide combined with dexamethasone resulted in significantly improved response rates and significantly prolonged median time to progression (TTP) and overall survival (OS) compared with dexamethasone alone. This current sub-analysis of lenalidomide plus dexamethasone therapy assessedwhether there was a survival benefit in maintaining patients on therapy after achieving their best response andwhat the impact of early discontinuation on TTP and OS was.Methods: Of the 353 patients from MM-009 and MM-010 treated with lenalidomide plus dexamethasone, 32 did not respond. Of the remaining 321 responding patients, 214 had a partial response (PR) or better and 107 patients had stable disease (SD). In this post-hoc sub-analysis, we first assessed the outcome of continuing treatment for ≤10 months vs. >10 months in all 321 patients who achieved SD or better, after they achieved their best response. In this landmark analysis, OS was measured from the time of achieving best response to death from any cause or to last contact. In a second analysis, we assessed the impact of early discontinuation due to adverse events or withdrawn consent on OS and TTP in all patients who achieved SD or better. Therefore, we excluded patients who discontinued treatment due to disease progression, death, or lack of efficacy. Patients who achieved SD or better and who continued on therapy were compared with those who discontinued. OS and TTP were assessed from time of randomization.Results: In the landmark analysis, of the 321 responding patients (≥PR, n=214; SD, n=107), 223 patients received treatment for ≤10 months after achieving their best response and 98 patients for >10 months after achieving their best response. Patients who continued therapy for >10 months after achieving their first best response had significantly longer OS vs. those who received therapy for ≤10 months (not reached vs. 23.4 months; p<0.0001). At 24 months after achieving their best response, significantly more patients were alive if they continued therapy >10 months vs. ≤10 months (93.8% vs. 48.4%, p<0.0001). In the second analysis, in order to evaluate the impact of discontinuation in patients achieving SD or better, we excluded 134 patients due to disease progression, death, or lack of efficacy. Of the remaining 187 responding patients, 72 discontinued treatment for AE (n=42) or withdrew consent (n=30), while the remaining 115 patients continued treatment. Median OS and TTP were significantly longer for patients who continued vs. those who discontinued treatment (median OS: not reached vs. 29.5 months, p<0.0001; median TTP: not reached vs. 13.6 months, p<0.0001).Conclusions: In patients achieving SD or better, prolonged duration of treatment was associated with significantly longer OS and TTP. In contrast, early discontinuation of treatment led to reduced OS and TTP. Therefore, efforts should be made to manage adverse events while maintaining patients on therapy. Furthermore, maintaining treatment with lenalidomide and dexamethasone after achieving the optimal response ensures a significant improvement in OS for patients with relapsed or refractory MM.

Advances in the Treatment of Metastatic Non–Small-Cell Lung Cancer With Chemotherapy and Targeted Agents

In Brief The treatment of non–small-cell lung cancer (NSCLC) is constantly evolving. Recent advances in both the front-line and relapsed/refractory setting have improved patient outcome, whereas in the past, best supportive care was considered the only viable option for patients with advanced or metastatic NSCLC. Improvements in chemotherapeutic regimens and the development of novel targeted agents have resulted in incremental improvements in overall patient survival. The antiangiogenic agent bevacizumab has recently yielded a clinically significant improvement in response rate, progression-free survival, and overall survival for patients with previously untreated nonsquamous recurrent or advanced (stage IIIB/IV) metastatic NSCLC. In the second- and third-line settings, docetaxel, pemetrexed, and inhibitors of the epidermal growth factor receptor, such as erlotinib, have contributed to increased overall time to progression and overall survival. Ongoing clinical trials are currently focusing on generating further improvements in patient outcome by combining novel targeted agents and redefining patient selection criteria to enrich the population that will ultimately receive the optimal therapy for maximal benefit. When examining advanced/metastatic non–small-cell lung cancer treatment options and outcomes historically, a clear advantage with the use of chemotherapy has only been recently realized. It is hoped that the addition of targeted agents to these standard regimens will further improve survival. Recent studies have demonstrated a survival advantage for antiangiogenic or epidermal growth factor receptor-targeted therapy when added to standard chemotherapy for non–small-cell lung cancer, and ongoing studies are addressing the use of other novel agents in this setting.

Myelodysplastic Syndrome: A Study of VA Population.

Background: Epidemiology and outcome of myelodysplastic syndromes (MDS) in the United States is not well recognized. MDS became reportable to the Surveillance, Epidemiology, and End Results program (SEER) in 2001. Only one study is published examining the SEER data between 2001–2003 on MDS incidence, epidemiology and outcome. We report first study of MDS among large population in the Veteran Affair system.Methods: There are approximately 127 VA Medical Centers diagnosing and/or treating Cancer patients. The data collected by the medical centers cancer registries is aggregated as the VA Central Cancer Registry (VACCR) and is maintained by the Chief Program Office for Oncology at VA in Washington DC. We used the VACCR to analyze VA patients with MDS diagnosed between 1995 and 2005. The data was downloaded from the database using ICD-03 histology codes for MDS. Data was entered and analyzed using bio-statistical software SPSS. Kaplan-Meier curves were used for estimates of overall survival, chi square for comparison of categorical variables and t-test for continuous variables.Results: Between 1995 and 2005, 1411 MDS cases were registered in the VACCR database. The median age was 75 years. Among those 1379 (97.7%) were males and 1196 (84.4%) were white patients, 171 (12.1%) black, and 44 (3.5%) other race. Majority of cases were reported as MDS, NOS 935 (66.3%), Refractory anemia (RA) 180 (12.8%), Refractory anemia with ring sideroblasts (RARS) 105 (7.4%), Refractory anemia with multilineage dysplasia (RCMD) 22 (1.6%), 5 q syndrome 13 (0.9%), Refractory anemia with excess blasts (RAEB) 105 (7.4%), Refractory anemia with excess blast in transformation 17 (1.2%), and therapy related MDS (t-MDS) 34 (2.4%). No IPSS data were available. The median overall survival (OS) was 1.8 year (95% CI 1.5–2.1). The 3 year and 5 year overall survival was 30% and 22% respectively. The median OS for RA patients was 3.7 year, RARS 4.9 year and for RAEB was 0.8 year. No difference was observed in OS between whites and black (median OS 1.73 versus 2.65, p value 0.28). Their was a non statistically significant trend for improvement of OS in patients diagnosed in 2004–2005 compared to 1995–2003 (time where azacitidine and lenalidomide were approved) median OS of 3.2 versus 1.8 (p value 0.64).Conclusion: This is the first report of MDS case series in the VA system. Outcome is similar to what is described in literature and SEER data (3 Year OS was 30% in our VA population study compared to 35% in recently published SEER data). No racial disparities are observed in outcome. A trend towards better overall survival is noted in the last 2 years since approval of new treatment options. Coding for WHO subtypes, IPSS and treatment options should be considered in all large MDS registries.

Emerging Role of Rexinoids in Non-Small Cell Lung Cancer: Focus on Bexarotene

Although the introduction of third-generation antineoplastic agents in the treatment of non-small cell lung cancer has led to modest improvements in overall patient survival, lung cancer continues to be the leading cause of cancer-related death worldwide, and improved therapies are needed. Retinoids play a critical role in the regulation of cell division, growth, differentiation, and proliferation, and they represent an exciting new avenue for targeted therapy. Several synthetic retinoids that bind to retinoic acid receptors are currently being investigated in a variety of tumor types. However, many of these agents have been associated with cheilitis, skin reactions, severe headache, and hypertriglyceridemia. Synthetic agents that bind specifically to retinoid X receptors are called rexinoids. Bexarotene (Targretin; Ligand Pharmaceuticals; San Diego, CA; http://www.ligand.com) is a novel, multitargeted synthetic rexinoid that is currently being investigated in the treatment of non-small cell lung cancer. Phase I and II studies have demonstrated that bexarotene is safe and well tolerated in this patient population either alone or in combination with chemotherapeutic agents. Patients treated with bexarotene experience manageable adverse events at reduced levels compared with retinoic acid receptor-specific retinoids. Bexarotene in combination with chemotherapeutic agents has demonstrated an encouraging median survival for patients with advanced non-small cell lung cancer compared with historical results with combination chemotherapy alone. Two phase III trials are currently under way to fully characterize the role of bexarotene in the treatment of this disease. The purpose of this review is to explore the rationale for rexinoids in the treatment of malignancies and to discuss the clinical profile of bexarotene in the treatment of non-small cell lung cancer.

"One to three" or "four or more"?: selecting patients for postmastectomy radiation therapy.

A review of randomized trials suggesting an improvement in overall patient survival with postmastectomy radiation therapy revealed that most patients in these studies had three or fewer positive axillary lymph nodes. Therefore, it is logical to consider using postmastectomy radiation therapy in all lymph node positive patients, not just those with four or more positive lymph nodes.

Hodgkin's disease. Survival and histologic classification in a general medical center, 1952-1971.

A retrospective review of Hodgkin' disease at a general referral center from 1952 to 1971 was carried out. Available pretreatment biopsies were classified by the modified Lukes-Butler classification into histologic types by a single pathologist, who then reviewed the same material 6 months later without the knowledge of his previous conclusions or patient identification. There was 95% concordance between original and review classifications. The frequency distribution of age of diagnosis and sex were unchanged over the time period of the study. The frequency distribution of histologic types was also unchanged when 5-year intervals were compared. However, there was no case of the lymphocytic-predominance type in the first half of the study period, which was significantly different from the incidence of this type in the second half of the study period. Survival rates showed no improvement in overall patient survival over the time period of the study but significant differences in the survivals of patients with different histologic types were noted.