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Temsirolimus: A New Drug for Refractory Mantle Cell Lymphoma
On July 23, 2009, the European Medicines Agency (EMEA) recommended that the EU marketing authorization of Wyeth’s temsirolimus (Torisel®) be expanded to include the treatment of adult patients with relapsed and/or refractory mantle cell lymphoma. Currently, temsirolimus is indicated for the first-line treatment of patients with advanced poor-risk renal cell carcinoma. Results from the phase III trial supporting this new indication were presented in the August issue of primeLINESSM.
Highlights from the 13th World Conference on Lung Cancer
More than 6000 lung cancer specialists, medical professionals, and researchers from around the world gathered in San Francisco, California, from July 31 - August 4 for the 13th World Conference on Lung Cancer (WCLC), organized by the International Association for the Study of Lung Cancer (IASLC). Major topics discussed at the meeting included the new TNM (Tumor, lymph Nodes, Metastases) staging system, the role of molecular markers for lung cancer, front-line therapy with epidermal growth factor receptor (EGFR) tyrosine-kinase inhibitors (TKIs), maintenance therapy, and personalized medicine.
The 7th edition of the TNM staging system, approved by the American Joint Committee on Cancer and the International Union Against Cancer, was unveiled at this meeting. The new staging system for lung cancer is based on a large international database of more than 100,000 records from patients with lung cancer and the most extensive statistical analysis involving rigorous internal and external validation. The revised staging system provides a detailed common nomenclature and more clearly defines the prognosis for patients with non-small cell lung cancer (NSCLC) through the addition of many new patient subgroups and reclassification of some previous subgroups. Although the new system is important in guiding the therapeutic decision-making process, treatment must still be individualized.
The role of biomarkers in personalizing therapy for lung cancer was widely discussed during the congress; indeed, EGFR mutation status was discussed as an example of a predictive marker that should be used in clinical practice to individualize treatment with TKIs. In a study presented during the Presidential Symposium, data demonstrated that the nature of KRAS mutations may vary by tumor type and, also, within lung cancer histologic subtypes, as well as between smokers and nonsmokers. These results suggest that more research is warranted to determine the predictive value of KRAS mutations for patients with lung cancer. In addition to EGFR and KRAS, research was presented on the potential of genomic signatures to individualize treatment and predict sensitivity to therapeutic agents in patients with lung cancer.
Conclusions of note from other studies presented at this meeting included:
- Phase III IPASS (IRESSA Pan Asia Study) trial results demonstrated longer progression-free survival (PFS) and greater objective response rates with single-agent gefitinib (IRESSA™) compared with carboplatin/paclitaxel chemotherapy in patients with EGFR mutations (exon 19 deletions subgroup and L858R mutation subgroup). Similar responses were observed in a number of patients with T790M mutations, which have previously been reported to be associated with resistance to EGFR TKIs.
- Results of a randomized phase III study of single-agent gefitinib versus chemotherapy with gemcitabine (Gemzar®) /cisplatin as first-line treatment for never-smokers with advanced or metastatic lung adenocarcinoma demonstrated that treatment with gefitinib resulted in a higher response rate, significantly better PFS, and better toxicity profile compared to chemotherapy. Progression-free survival was also analyzed in patients with known EGFR mutation status; it was found that mutation-negative patients experienced significantly shorter PFS than mutation-positive patients in the gefitinib arm, but no difference was observed for these subgroups in the chemotherapy arm. Although gefitinib did not improve survival over standard chemotherapy, results of this study suggest that gefitinib may be a reasonable first-line therapy in patients with adenocarcinoma who have never smoked.
- Results from the phase III SATURN trial, which evaluated the efficacy and tolerability of erlotinib (Tarceva®) as maintenance therapy following non-progression on platinum-based chemotherapy, demonstrated a statistically significant prolongation of PFS benefit (of 41% to 45%) for patients with NSCLC treated with erlotinib compared to placebo. Furthermore, an improvement in PFS was observed regardless of gender, smoking history, ethnicity, or EGFR or KRAS mutation status.
- A prospective biomarker analysis was also performed in the SATURN trial. Tumor samples were tested for EGFR expression, EGFR gene copy number, and EGFR and KRAS mutation status. The results of this analysis demonstrated clinical benefit of erlotinib regardless of biomarker status. Epidermal growth factor receptor mutation status was shown to be a strong positive predictor of PFS benefit with erlotinib. KRAS mutation status was a negative prognostic factor, but did not show predictive value for benefit with erlotinib.
- Treatment with vandetanib, a dual inhibitor of EGFR and vascular endothelial growth factor receptor, in combination with docetaxel chemotherapy resulted in a 21% improvement in PFS compared to chemotherapy alone in previously treated patients with advanced NSCLC.
- A meta-analysis of 4 randomized controlled trials that independently reported improvements in overall survival (OS) for platinum-based chemotherapy plus cetuximab (Erbitux®) as first-line therapy in patients with advanced NSCLC confirmed the clinical benefits of addition of cetuximab for OS, PFS, and objective response rate.
- A follow-up of the much awaited randomized NATCH (Neoadjuvant-Adjuvant Taxol Carboplatin Hope) trial comparing preoperative and adjuvant chemotherapy with surgery alone in patients with operable NSCLC did not show a significant difference in 5-year disease-free survival (DFS) and OS with preoperative or adjuvant chemotherapy compared to surgery alone. Peter Goldstraw, MD, from the Royal Brompton Hospital in London, commented that the failure to reach statistical significance may have been related to the inclusion of clinical stage I and node-negative patients, who are not generally believed to benefit from non-directed chemotherapy. “It doesn’t show that chemotherapy doesn’t work,” he said. “I think what it shows is that we’ve got to be very, very selective.”
Should Bisphosphonates Routinely Accompany Adjuvant Therapy for Breast Cancer?
This question has been a hot topic since results from the Austrian Breast and Colorectal Cancer Group (ABCSG)-12 trial became available. Data from ABCSG-12 suggested that the addition of a nitrogen-containing bisphosphonate (zoledronic acid, Zometa®), used for prevention of treatment-related bone loss, improved clinical outcomes for women with early breast cancer beyond those achieved with endocrine therapy alone. Some have called the results “practice changing,” while others are not as swayed by these findings. In Comments and Controversies in the recent issue of the Journal of Clinical Oncology, Bedard and colleagues discussed this topic. After thoughtful review of all relevant data, they indicated that the final verdict should be withheld until results from the large AZURE and NSABP B-34 trials become available, even though a delay in reporting of the efficacy analyses raises concern that the event rates may be lower than expected, or that the addition of a bisphosphonate may not significantly affect the outcome. The authors concluded that, because of the remarkable treatment effect and minimal toxicity demonstrated in ABCSG-12, it is reasonable to consider the advantages of early rather than late administration of zoledronic acid every 6 months in premenopausal women receiving adjuvant ovarian suppression. In this clinical situation, bisphosphonates may prevent treatment-related bone loss and subsequent fractures and, as an added benefit, possibly reduce the risk of breast cancer recurrence.
J Clin Oncol. 2009;27(25):4043-4046.
Anthracyclines in Early Breast Cancer: On Their Way Out?
Currently, there is an ongoing debate about the importance of anthracyclines in the adjuvant treatment of breast cancer. For decades, anthracyclines have been the standard of care for women with breast cancer, but the emergence of important new data on the predictive power of human epidermal growth factor receptor-2 (HER2) and topoisomerase II alpha (Topo2α) have led to suggestions that anthracyclines might be discarded in the treatment of patients with HER2-positive early breast cancer. In a recent article in HemOnc Today (July 10, 2009), Dennis Slamon, MD, PhD, director of clinical/translational research at the University of California–Los Angeles’ Jonsson Comprehensive Cancer Center, has stated that it is time to phase out anthracyclines due to overwhelming data indicating that only a small subset of women with breast cancer seem to benefit from this class of agents. However, in a recent article in the Journal of Clinical Oncology, an internationally recognized panel of experts reviewed the data and concluded that it may be premature to abandon anthracyclines (J Clin Oncol. 2009 Aug 17. [Epub ahead of print]). It was noted that instead of abandoning anthracyclines, less cardiotoxic formulations (eg, liposomal doxorubicin) and schedules should be evaluated in prospective trials, comparing anthracycline/taxane schedules with non–anthracycline-containing regimens. Furthermore, because not all patients benefit from anthracyclines, the expert panel suggested the identification of methods to select patients that could benefit.
Patients with Breast Cancer and Isolated Tumor Cells or Micrometastases in Regional Lymph Nodes Need Adjuvant Therapy
Axillary lymph node status is considered the most important prognostic factor in patients with breast cancer. Prior to the sentinel node (SN) biopsy period (before 1995), isolated tumor cells (ITCs) and micrometastases were mainly undetected and patients with a favorable outcome continued regular follow-up after local treatment. However, thorough examination of the SNs by serial sectioning and immunohistochemical staining allows for detection of ITCs (staged as pN0[i+], with deposits ≤0.2 mm) or micrometastases (staged as pN1mi, with deposits >0.2 to ≤2.0 mm), making the approach followed during the pre-SN biopsy period appear less clear. In The Netherlands, systemic adjuvant therapy is not recommended per guidelines for women with low-risk breast cancer with ITCs, and no guidelines exist with respect to systemic adjuvant therapy for patients with breast cancer with nodal micrometastases. As a result, some patients receive adjuvant therapy, while others do not.
The MIRROR (Micrometastases and Isolated Tumor Cells: Relevant and Robust or Rubbish?) study was conducted in patients in The Netherlands to determine the association, if any, between ITCs or micrometastases in regional lymph nodes and clinical outcome in breast cancer patients who underwent SN biopsy and who did or did not receive systemic adjuvant therapy. This study identified all patients who had a SN biopsy for breast cancer before 2006 and had favorable primary tumor characteristics and ITCs or micrometastases in the regional lymph nodes, while patients with node-negative disease were randomly selected from the years 2000-2001. The following 3 patient cohorts were assessed: node-negative with no adjuvant-therapy (n = 856), node-positive (ITC or micrometastases in LN) with no adjuvant-therapy (n = 856), and node-positive (ITC or micrometastases in LN) with adjuvant-therapy (n = 995). Patients with ITCs who did not receive adjuvant therapy had a significantly reduced 5-year DFS rate (primary endpoint) compared to those in the node-negative, no adjuvant-therapy cohort (77.2% vs 85.7%, respectively; P<.001); among patients with micrometastases the DFS rates were 75.9% vs 85.7%, respectively (P = .002). Moreover, women with ITCs or micrometastases who did not receive adjuvant therapy had a significantly reduced DFS rate compared with those in the node-positive, adjuvant-therapy cohort (76.5% vs 86.2%, respectively; P<.001).
Results from this study showed a strong association between ITCs or micrometastases in the regional lymph nodes and a reduced 5-year DFS rate in women with low-risk breast cancer who received no adjuvant therapy. Additionally, the study showed a significant improvement in DFS in patients with ITCs or micrometastases who received adjuvant therapy.
N Engl J Med. 2009;361(7):653-663.
Antitumor Activity of Abiraterone in Castration-Resistant Prostate Cancer
It has been suggested that castration-resistant prostate cancer (CRPC) frequently remains hormone-driven via adrenal hormones or intracrine synthesis. Patients who relapse despite castration may respond to further hormonal treatments, but these secondary endocrine therapies have been shown to be only modestly effective. Currently, many treatment options are being investigated for CRPC, one of which is abiraterone, an orally available hormonal therapy that blocks CYP17, the enzyme essential for androgen and estrogen production. By blocking CYP17, abiraterone inhibits testosterone production in the testes and in the adrenal glands and tumor cells.
To rapidly evaluate the antitumor activity of abiraterone acetate in chemotherapy-naïve patients with CRPC, a phase I study seamlessly expanded into a two stage, single-arm, phase II trial that included 42 chemotherapy-naïve patients with CRPC who experienced progression on multiple hormonal therapies. Abiraterone was administered continuously at 1000 mg once daily. The primary endpoint of the study was ≥50% prostate-specific antigen (PSA) decline at any time after 12 weeks of therapy, confirmed by a second PSA analysis 4 weeks later; the rate of PSA declines ≥30% was a secondary endpoint. This study also reported ≥90% PSA declines, radiologic changes, changes in circulating tumor cells (CTC) counts, and median time to PSA progression. The study was prospectively designed to allow addition of dexamethasone 0.5 mg/day to abiraterone for all patients at progression in order to reverse resistance by suppressing adrenocorticotropic hormone and steroids upstream of the CYP17 blockade. Nearly two-thirds (67%) of phase II patients had a decline in PSA of ≥50%, 70% experienced a decline of ≥30%, and declines of ≥90% were observed in approximately 20% of patients. The decline in PSA values was associated with partial responses (RECIST) in 9 of 24 (37.5%) patients with measurable disease on CT scan; overall, 66% of patients showed no progression at 6 months. A decline in CTC counts of ≥30% was shown in 12 of 17 (70%) of patients after treatment initiation with abiraterone. Median time to PSA progression on abiraterone alone was 225 days (range, 162 days to 287 days) for all phase II patients. Exploratory analyses in phase I/II patients (n = 54) showed that addition of dexamethasone at disease progression reversed resistance in 33% of patients, irrespective of prior dexamethasone treatment.
This study confirms that CYP17 inhibition with abiraterone results in declines in PSA levels and CTC counts, and radiologic responses in patients with CRPC. These findings also indicate that abiraterone may be activated by elevated hormone levels upstream of CYP17, supporting future evaluation of a combination of abiraterone plus low-dose corticosteroids to maximize efficacy and minimize toxicity (eg, syndrome of secondary mineralocorticoid excess). Indeed, this combination is currently being evaluated in a phase III clinical trial.
J Clin Oncol. 2009;27(23):3742-3748.
Axitinib: Another Targeted Therapy for Metastatic Renal Cell Carcinoma
Agents that target vascular endothelial growth factor (VEGF) signaling or mammalian target of rapamycin (mTOR) have shown benefit in patients with metastatic renal cell carcinoma (mRCC). Several of these agents, including the multitargeted TKIs sorafenib and sunitinib, are now approved in the US and EU for first-line or second-line treatment of mRCC. Axitinib, an oral inhibitor of VEGF receptors 1, 2, and 3, has demonstrated substantial activity in phase II trials evaluating patients with cytokine-refractory mRCC. In vitro, axitinib has shown to be more potent and selective against VEGF receptors than sunitinib or sorafenib. Combined with the fact that there is no complete cross resistance to antiangiogenic therapies in mRCC, researchers hypothesized that axitinib could provide clinical benefit in patients who received prior VEGF-targeted therapy.
An open-label, multicenter, phase II study was conducted to evaluate the efficacy and safety of oral axitinib 5 mg twice daily in patients with mRCC that was refractory to prior therapies, including, but not limited to, sorafenib. All 62 patients enrolled received prior sorafenib, while approximately 75% received at least 2 prior systemic treatments. Objective response rate was the primary endpoint and was 22.6%, and the median duration of response was 17.5 months. Median duration of PFS and OS were 7.4 months and 13.6 months, respectively. The most common grade 3 adverse events included hand-foot syndrome (16.1%), fatigue (16.1%), hypertension (16.1%), and diarrhea (14.5%).
These results demonstrate that axitinib is active and well tolerated in patients with sorafenib-refractory mRCC and in patients who have been treated with additional prior therapies. Axitinib is an addition to the armamentarium against renal cell carcinoma, which continues to expand. A randomized, phase III study is being conducted to compare the activity of axitinib versus sorafenib in patients with mRCC who are refractory to one prior first-line therapy, including sunitinib, cytokines, temsirolimus, or bevacizumab plus interferon alfa.
J Clin Oncol. 2009 Aug 3 [Epub ahead of print].
Denosumab Protects Bone in Men Receiving Androgen-Deprivation Therapy for Prostate Cancer
Androgen-deprivation therapy (ADT), achieved via surgical castration or chemical castration by using gonadotropin-releasing hormone (GnRH), is the standard first-line treatment for metastatic prostate cancer. Gonadotropin-releasing hormone agonists are also frequently used in the following situations: for nonmetastatic prostate cancer as adjuvant treatment in men with locally advanced disease who are undergoing radiation therapy, men with lymph node-positive disease treated with radical prostatectomy and pelvic lymphadenectomy, and patients with PSA relapse only. However, ADT adversely affects bone, causing increased bone resorption, decreased bone mineral density (BMD), and an increased risk of fractures in this patient population. Several drugs, including bisphosphonates and selective estrogen-receptor modulators, have shown to prevent bone loss associated with ADT, but published studies demonstrating an effect on fracture prevention are lacking. Denosumab is a human monoclonal antibody that specifically binds to the receptor activator of nuclear factor-κB ligand (RANKL), which is a key mediator of osteoclast formation, function, and survival.
A randomized, double-blind, phase III study was conducted to evaluate the effects of denosumab on BMD and fractures in men receiving ADT for nonmetastatic prostate cancer. Patients were randomized to denosumab 60 mg subcutaneously every 6 months (n = 734) or placebo (n = 734), and were followed for 3 years for safety and fracture evaluation. Primary endpoint was percentage change in BMD of lumbar spine at 24 months. At 24 months, denosumab-treated patients had a significant increase of 5.6% in BMD at the lumbar spine compared to a 1% loss in the placebo group (P<.001); significant between-group differences were observed as early as 1 month and sustained through 36 months. Additionally, denosumab significantly increased BMD at the hip, femoral neck, and distal third of the radius at all time points, while significantly decreasing the incidence of new vertebral fractures at 36 months (1.5% vs 3.9% for placebo, P = .006). Adverse event rates were similar between the 2 groups.
The authors concluded that the bi-annual administration of denosumab is associated with significant increases in BMD at all sites and a significant reduction in new vertebral fractures in men receiving ADT for nonmetastatic prostate cancer.
N Engl J Med. 2009;361(8):745-755.
Single-Agent Lenalidomide for Refractory Multiple Myeloma: Can We Avoid the Corticosteroid Effects?
Nearly all patients with multiple myeloma (MM) relapse after initial therapy and become refractory to treatment. Novel agents such as thalidomide (Thalomid®), bortezomib (Velcade®), and more recently, lenalidomide (Revlimid®), have improved treatment outcomes for patients with MM. Lenalidomide, an immunomodulating agent, combined with dexamethasone has demonstrated efficacy in two phase III trials evaluating patients with relapsed or refractory MM who have received ≥1 prior treatment regimen. Results from these trials supported the marketing approval of lenalidomide in both the US and EU. However, dexamethasone added to lenalidomide has been associated with dose-limiting toxicities such as deep-vein thrombosis (DVT), infections, and hyperglycemia; thus, it was important to investigate single-agent lenalidomide in MM, particularly in patients unable to tolerate steroids.
A multicenter, open-label, phase II trial was conducted to evaluate the efficacy and safety of lenalidomide monotherapy in patients with relapsed or refractory MM who received ≥2 prior treatment regimens; concomitant dexamethasone was not permitted. A total of 222 patients were treated with oral lenalidomide 30 mg once daily for 21 days, every 28 days, until disease progression or intolerance. Two-thirds of the patients had received ≥3 prior treatment regimens including thalidomide, bortezomib, or stem cell transplantation. Twenty-six percent of the patients had partial responses or better, with a minimal response rate of 18%. Response rates were comparable for patients who received ≤2 or ≥3 prior treatment regimens (45% vs 44%, respectively). Median values for time to progression (TTP), PFS, and OS were 5.2 months, 4.9 months, and 23.2 months, respectively. Moreover, the majority of grade 3/4 adverse events consisted of neutropenia (60%), thrombocytopenia (39%), and anemia (20%), which were manageable with dose reductions.
Based on these results, the authors concluded that lenalidomide monotherapy is active and well-tolerated in patients with relapsed and refractory MM. Furthermore, these findings provide a strong rationale for the use of single-agent lenalidomide in select patients, in steroid-sparing combination regimens, and as maintenance therapy.
Bendamustine Better than Chlorambucil for Chronic Lymphocytic Leukemia
Chronic lymphocytic leukemia (CLL) is the most common type of adult leukemia in Western countries. First-line treatment typically consists of chlorambucil, fludarabine, or fludarabine plus cyclophosphamide, either alone or in combination with rituximab. Despite improved outcomes demonstrated with fludarabine compared to chlorambucil in untreated patients with CLL, an unmet need exists for new and improved treatment options for patients with advanced CLL. Bendamustine (Treanda®), an intravenously administered alkylating agent, has demonstrated similar or higher overall response rates compared to chlorambucil in phase I/II trials in patients with advanced relapsed or refractory CLL. These results led to a randomized, open-label, multicenter, phase III trial, which enrolled 319 untreated patients with advanced (Binet stage B or C) CLL to receive bendamustine 100 mg/m2/day IV on days 1 and 2 (n = 162), or chlorambucil 0.8 mg/kg orally on days 1 and 15 (n = 157); treatment cycles were repeated every 4 weeks for a total of 6 cycles. Treatment response was assessed according to the National Cancer Institute Working Group criteria, and a blinded independent review committee made the final determination of response.
Overall, significantly more bendamustine-treated patients than chlorambucil-treated patients achieved a complete or partial response (68% vs 31%, P<.0001), and complete response rates were higher with bendamustine than chlorambucil (31% vs 2%). Bendamustine significantly prolonged median PFS compared with chlorambucil (21.6 months vs 8.3 months, P<.0001). In addition, bendamustine prolonged duration of remission by approximately 14 months compared with chlorambucil. The incidence of grade 3/4 adverse events was higher in the bendamustine than chlorambucil group (40% vs 19%), with severe infections occurring in 8% of bendamustine-treated patients and 3% of chlorambucil-treated patients.
These results showed that bendamustine is significantly more effective than chlorambucil, and with manageable toxicity, when used as first-line treatment in patients with advanced CLL. Data from this trial supported the US marketing approval of bendamustine for CLL in March 2008.
J Clin Oncol. 2009;27(26):4378-4384.
Surgery after Induction Chemoradiotherapy for Stage IIIb NSCLC
Management of locally advanced NSCLC remains a major challenge. Stage IIIb NSCLC is generally considered unresectable and is managed with chemotherapy with or without radiotherapy. Nevertheless, among patients with locally advanced stage IIIb NSCLC, there is a subgroup whose tumors are technically amenable to complete resection (eg, localized N3 or T4 disease). Recent surgical series suggested encouraging survival rates in patients with stage IIIb disease after induction chemoradiotherapy.
A multicenter, phase II study by the Swiss Group for Clinical Cancer Research (SAKK) was conducted to evaluate the efficacy and safety of neoadjuvant chemotherapy and radiotherapy followed by surgery in patients with potentially operable stage IIIb NSCLC. Patients received sequential therapy, consisting of 3 cycles of neoadjuvant chemotherapy (cisplatin with docetaxel) followed immediately by accelerated concomitant boost radiotherapy (44 Gy in 22 fractions) and surgery. Of the 46 patients enrolled, all received chemotherapy and 35 received radiotherapy. A total of 13 patients had N3 disease and 36 had T4 disease. Nearly 60% of patients (27/46) had complete resection, while a second surgical intervention was required in approximately 15% of patients (7/46). Event-free survival at 12 months (primary endpoint) was 54%. After a median follow-up of 58 months, the median OS was 29 months; estimated OS at 1, 2, 3, and 5 years was 67%, 52%, 47%, and 40%, respectively. The most common toxicities during chemotherapy were neutropenia (54%, grade 3/4) and febrile neutropenia (20%), while the main toxicity after radiotherapy was esophagitis (29%; mostly grade 2).
Several limitations of the study were mentioned, including recently changed staging tools that might have led to stage migration, the small size of the trial, and a selected patient population. However, these results demonstrate that, for a subset of patients with stage IIIb NSCLC, treatment with neoadjuvant chemotherapy and radiotherapy followed by surgery is feasible, and toxicities associated with chemotherapy and radiotherapy are manageable. Ongoing phase III trials will help clarify the role of radiotherapy and surgery in locally advanced NSCLC.
Lancet Oncol. 2009;10(8):785-793.
ADDITIONAL PUBLICATIONS WORTH READING
- Vardiman JW, Thiele J, Arber DA, et al. The 2008 revision of the World Health Organization (WHO) classification of myeloid neoplasms and acute leukemia: rationale and important changes. Blood. 2009;114(5):937-951. This article highlights the recently revised classification of myeloid neoplasms and acute leukemia with the goal of familiarizing hematologists, clinical scientists, and hematopathologists with the major changes in the classification as well as the rationale for those changes.
- Bellmunt J, Theodore C, Demkov T, et al. Phase III trial of vinflunine plus best supportive care compared with best supportive care alone after a platinum-containing regimen in patients with advanced transitional cell carcinoma of the urothelial tract. J Clin Oncol. 2009 Aug 17 [Epub ahead of print]. This article reports the results of
a study comparing OS between patients with advanced transitional cell carcinoma of urothelial tract receiving vinflunine plus best supportive care (BSC) or BSC alone. - Motzer RJ, Hutson TE, Tomczak P, et al. Overall survival updated results for sunitinib compared with interferon alfa in patients with metastatic renal carcinoma. J Clin Oncol. 2009;27(22):3584-3590. This article reports final survival analysis, efficacy and safety data of a randomized phase III trial comparing sunitinib with interferon alfa in metastatic renal cancer.
- The Big I-98 Collaborative Group, Mouridsen H, Giobbie-Hurder A, et al. Letrozole therapy alone or in sequence with tamoxifen in women with breast cancer. N Engl J Med. 2009;361(8):766-776. This article reports the findings of the randomized phase III double-blind Breast International Group 1-98 (BIG 1-98) trial that evaluated postmenopausal women with endocrine hormone receptor–positive breast cancer receiving either a sequence of letrozole and tamoxifen for 5 years or letrozole alone (as monotherapy) for 5 years. Also included is the update of the monotherapy arms analysis at 76-months follow-up, comparing 5 years of letrozole alone versus 5 years of tamoxifen alone following surgery. (See the primeLINESSM ASCO Edition, June 2009)
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| Expert PracticeSM in Genitourinary Malignancy 10 October 2009 | Brussels, Belgium | Contemporary Strategies for Breast Cancer Management: Practical Solutions for Important Issues 22 October 2009 | Yokohama, Japan |
