ASCO 2015 News 1, 3-5, 9–13 | Bilateral Prophylactic Mastectomy
14
| CUSTOM ‘Basket’ Trial
VOLUME 6, ISSUE 10
30
JUNE 10, 2015
Editor-in-Chief, James O. Armitage, MD | ASCOPost.com
Clinical Trials, Drug Costs, and Restoring the Primacy of the Patient Volunteer
ASCO 2015 Plenary Report
CheckMate 067: Dual Checkpoint Blockade Proves Effective in Advanced Melanoma By Caroline Helwick
By Laurence H. Baker, DO
n advanced melanoma, combination treatment with nivolumab (Opdivo) and ipilimumab (Yervoy) more than doubled the median progression-free survival time over ipilimumab alone in the CheckMate 067 trial. That said, single-agent nivolumab proved almost as powerful in patients expressing the programmed cell death ligand 1 (PD-L1). The findings from CheckMate 067, the first phase III trial to evaluate the combination of anti–PD-1 and anti–CTLA-4 agents, were presented at the Plenary Session of the 2015 ASCO Annual Meeting by Jedd Wolchok, MD, PhD, Chief of the Melanoma and Immunotherapeutics Service at Memorial Sloan Kettering Cancer Center, New York.
Toward Precision Immunotherapy “PD-L1 expression is not a binary discriminator of absolute benefit, but this trial is a first effort to try to introduce a precision aspect to immunotherapy.
In this study, we see it’s a way to initiate meaningful conversations between patients and clinicians about whether a combination [nivolumab/ipilimumab] is the right thing for them, vs nivolumab alone,” he told The ASCO Post. Jedd Wolchok, MD, PhD Some experts, however, were more tempered in their impression of PD-L1 as a potential biomarker. Study discussant Michael B. Atkins, MD, Deputy Director of the Lombardi Cancer Center at Georgetown University, a key figure in the PD-1 research story, said much more work is needed before involving PD-L1 expression in patient selection. “Even with a high threshold for positivity, which greatly enriched the biomarker-positive group in this trial, the
“What’s past is prologue.” ©ASCO/Scott Morgan 2015
I
continued on page 9
ASCO Annual Meeting
Mismatch Repair Deficiency Predicts Benefit With Pembrolizumab in Colorectal Cancer By Caroline Helwick
A
Almost two-thirds of colorectal cancer patients whose tumors demonstrated mismatch repair deficiency responded to pembrolizumab (10 mg/kg every 2 weeks), whereas none with mismatch repair– proficient tumors responded, reported Dung T. Le, MD, of the Kimmel Cancer Center at Johns Hopkins University, Baltimore. “This is the first study to use genetics to guide immunotherapy,” Dr. Le noted. “Mismatch repair–deficient tumors are highly responsive to checkpoint blockade This is the first study to use genetics with anti–PD-1 agents.”
©ASCO/Max Gersh 2015
genetic marker to predict response to anti– PD-1 (anti-programmed cell death protein 1) antibodies may have emerged in colorectal cancer, a tumor type that is a newcomer to the anti–PD-1 ballgame. In a phase II study of colorectal cancer patients treated with pembrolizumab (Keytruda), the presence of mismatch repair deficiency within the tumor robustly predicted benefit, investigators reported at the 2015 ASCO Annual Meeting.1
to guide immunotherapy. Mismatch repair–deficient tumors are highly responsive to checkpoint blockade with anti–PD-1 agents.
Send your comments to editor@ASCOPost.com
—Dung T. Le, MD
High Mutational Load May Be Needed
—William Shakespeare
T
oday, a cancer drug under study in a clinical trial is commonly provided for a finite period of time after the study closes to accrual. If that drug were not yet U.S. Food and Drug Administration (FDA)-approved when the study began, the complimentary drug supply to patients would end following FDA approval. In order to continue therapy with the drug, it would become the patient’s responsibility to purchase it. But this was not always the case. The following commentary is not meant to continued on page 94
Dr. Baker is Professor of Internal Medicine and Pharmacology, Division of Hematology/Oncology, University of Michigan Medical School, Ann Arbor. Disclaimer: This commentary represents the views of the author and may not necessarily reflect the views of ASCO.
MORE IN THIS ISSUE Oncology Meetings Coverage ASCO Annual Meeting �����1, 3–5, 9–13, 95 ASBS Annual Meeting ���������������������� 14, 17 AUA Annual Meeting �����������������������22–24 AACR Annual Meeting ����������������������������26 Robert L. Coleman, MD, on Advanced Ovarian Cancer �������������������������28 Direct From ASCO �������������������������� 46–49 Kim Margolin, MD, on Immune Checkpoint Inhibition �����������������53 In Memoriam ���������������������������������������������� 81 Fracture Risk After Stem Cell Transplant ��������������������������������������������������87
Mismatch repair deficiency occurs in up to 20% of sporadic colorectal cancers and all colorectal cancontinued on page 10
A Harborside Press® Publication