ASCO Updates

So the American Society of Clinical Oncology Conference is going on right now in Chicago.  My original plan was to actually attend as a patient advocate but given the last few weeks decided to stay home and take it easy this weekend.

We all know that in the last year + there have been some great advances in the treatment of Melanoma.  You have Ipi and Zelboraf (what I'm taking right now) that were approved by the FDA last year.  There are also lots of clinical trials going on.  One that folks are talking about a lot lately is the anti-PD1 trial.  I'm attaching below an article from the ASCO daily news talking about anti-PD1.  I just find it entertaining that the PD = programmed death lol!  There are lots of drug companies right now rushing to perfect this treatment.

As I see more updates from ASCO I'll post them!
Cheers,
Erin


ASCO Daily News > CRA2509 


Inhibition of PD-1 on T Cells

Blocking the programmed death-1 receptor on activated T cells yielded objective responses in some patients with advanced non-small cell lung cancer, melanoma, and renal carcinoma, suggesting that recent successes with immunotherapy are continuing. Suzanne Louise Topalian, of Johns Hopkins University Sidney Kimmel Comprehensive Cancer Center in Baltimore, presented results from a phase I study of the new agent BMS-936558 during the Clinical Science Symposium – Immune Checkpoint Strategies on Saturday (Abstract CRA2509).
Once activated, immune T cells begin to express programmed death-1 (PD-1). By expressing the ligand PD-L1, tumor cells can co-opt this system and send a signal that can deactivate the T-cells, thereby protecting themselves from attack. “Anti-PD-1 antibody blocks this interaction, so it blocks this biochemical shield that is created by the tumor to protect itself, thereby enabling T-cell destruction of tumor cells,” Dr. Topalian said.
BMS-936558 is a fully human monoclonal antibody that blocks PD-1. In this dose-escalation study, 296 patients received IV every second week of BMS- 936558 at doses ranging from 0.1 to 10.0 mg/kg. A total of 104 patients had melanoma, 122 had non-small cell lung cancer (NSCLC), 34 had renal cell carcinoma (RCC), 19 had colorectal cancer, and 17 had castration-resistant prostate cancer; all had progressive disease after at least one standard therapy. The median duration of therapy was 15 weeks, with a maximum of 120 weeks.
The maximum tolerated dose was not reached over the course of the study; grade 3-4 adverse events occurred in 14% of patients, and the most common adverse events of any grade were fatigue, rash, and diarrhea. Fifteen of the 296 patients (5%) discontinued treatment due to adverse events. Notably, nine patients had pneumonitis, and three of these patients (1% of total cohort) died. Dr. Topalian said that lower grade pneumonitis can be treated by stopping the drug or with steroids.
Among patients who received at least two cycles of the study drug, complete or partial response was observed in patients with melanoma, NSCLC, and renal cell carcinoma. Of the 94 evaluable melanoma patients, 28% had an objective response; in 33 RCC patients, 27% had a response; and in 76 NSCLC patients 18% showed some response. Topalian said that the response in NSCLC was most surprising, as this malignancy has proven refractory to immune-based therapies in the past.
The responses appeared to be durable. Among 31 patients with an objective response who had been followed for at least one year, 20 had a response lasting at least one year. Six melanoma patients, five NSCLC patients, and nine RCC patients had stable disease lasting at least 24 weeks.
The investigators performed immunohistochemistry on pre-treatment tumor biopsies in 42 patients to test PD-1 ligand’s (PD-L1) efficacy as a biomarker for response. Nine of 25 of those patients with PD-L1-positive tumors achieved an objective response (36%), while none of the 17 with PD-L1-negative tumors showed any response (p = .006). Dr. Topalian said this was promising, and that the use of PD-L1 as a biomarker will be explored further.
James Allison, of Memorial Sloan- Kettering Cancer Center, was the discussant for the session, and he said the response in multiple tumors and especially NSCLC make this a promising avenue of research,¡ though it was surprising that no responses were seen in prostate cancer or in colorectal cancer patients.
Dr. Allison also noted that it will most likely be in various combinations that immunotherapies such as this will eventually be most effective. “How do we start combining these to get up to the point where we’re not getting a successful outcome in just a fraction of patients?” he asked. He added that the results with PD-1 indicate that the success with the immunotherapeutic agent ipilimumab, approved last year by the FDA, will likely continue.
This early success with BMS-936558 will lead to controlled clinical registration trials of the agent soon, Dr. Topalian said, specifically in patients with NSCLC, melanoma, and renal cell carcinoma.

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