February 2016, Vol. 5, No. 1

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In Newly Diagnosed Myeloma Patients, Triplets Preferred

Brian G.M. Durie, MD

ASH 2015, ASH Highlights

Brian_Durie98pxWhile the cost of treating newly diagnosed patients is greatly increased with the use of 3 drugs, doublets should not be considered adequate, and triplets should be the standard of care, according to results from a randomized trial.

The use of triplets—including a proteasome inhibitor, immunomodulatory drug (IMiD), and steroid—has been growing in the United States, and lenalidomide was approved in 2015 for use up front. No randomized trial, however, had proved triplets superior to lenalidomide/dexamethasone alone.

This has now been accomplished in the phase 3 SWOG S0777 trial. Brian G.M. Durie, MD, of the International Myeloma Foundation and Cedars-Sinai Comprehensive Cancer Center, Los Angeles, CA, presented the comparison of bortezomib/lenalidomide/low-dose dexamethasone (VRd) with lenalidomide/dexamethasone (Rd) alone. Both arms received maintenance Rd until progression or unacceptable toxicity.

VRd significantly improved response rates, progression-free survival, and overall survival, Durie reported.

“VRd induction followed by continuous Rd is a potential new standard of care,” he maintained. Sagar Lonial, MD, Professor, Hematology and Medical Oncology, Emory University’s Winship Cancer Institute, Atlanta, GA, said the results solidify the use of 3 drugs as the optimal first-line therapy. A triplet containing a proteasome inhibitor, IMiD, and steroid has “come of age” as the standard of care, he said.

All Outcomes Improved with Triplet

SWOG S0777 randomized 525 patients to VRd or Rd, with both arms offered maintenance Rd.

Overall response rates were 81.5% with VRd and 71.5% with Rd, which included complete responses in 15.7% and 8.4%, respectively. Median progression-free survival was 43 months with VRd and 31 months with Rd (hazard ratio [HR], 0.712; 1-sided P = .0018). Median overall survival was 75 months versus 64 months, respectively (HR, 0.709; 2-sided P = .0250).

The regimens were generally well tolerated; adverse events grade ≥3 were significantly more common in the VRd arm, including neurologic events (33% vs 11%), pain (12% vs 4%), sensory toxicity (23% vs 3%), and gastrointestinal side effects (22% vs 8%).

Durie pointed out that bortezomib was administered intravenously twice a week, which was the way the drug was typically given in 2008 when the study began. Subcutaneous or less frequent administration of bortezomib might have ameliorated some of the toxicity, he suggested.

According to Lonial, “We have now established that a 3-drug induction of an IMiD and proteasome inhibitor is the best combination. Three drugs are better than 2, with the exception of frail patients.”

San Antonio Breast Cancer Symposium - February 12, 2016

ESR1 Mutations Portend Worse Survival in ER+ Advanced Breast Cancer

A “liquid biopsy” was able to detect 2 mutations in the estrogen receptor 1 (ESR1) gene that predicted worse overall survival (OS) in women with estrogen receptor–positive (ER+), metastatic breast cancer who were originally enrolled in the BOLERO-2 clinical trial.The presence of a D358G and/or Y537S mutation in the ESR1 [ Read More ]

San Antonio Breast Cancer Symposium - February 12, 2016

Omit Chemotherapy for Premenopausal Luminal A Breast Cancer?

Younger patients with luminal A subtype breast cancer may not need chemotherapy, according to a Danish trial presented at the 2015 San Antonio Breast Cancer Symposium. Luminal A biological subtype breast cancer has an excellent prognosis, even in high-risk patients, the study suggests.“A large body of evidence suggests that luminal [ Read More ]