ASCO 2010|May 15, 2011 9:40 pm

Discussed Poster Session ASCO 2010

After the relative excitement of the previous two days, the discussed melanoma poster session on Monday June 7 seemed pretty muted. I went through the posters, listened to the discussants, and below list my personal Top 5, in no particular rank order, along with two honorable mentions. The numbers that keep coming to the front of my mind are the PFS/OS stats for any treatment trial, in light of the 6 month OS and 10 month OS in the “control” and treatment arms of the ipi plenary session trial from June 6.

Two posters with Avastin (bevacizumab):

#1: Phase II trial of bevacizumab and high-dose interferon alpha-2b in metastatic melanoma.

#2: First-line temozolomide (TEM) combined with bevacizumab (BEV) in metastatic melanoma (MM): A multicenter phase II trial (SAKK 50/07).

These are two trials continue the long look that Avastin is getting in melanoma. Last year, the BEAM trial (taxol/carbo/Avastin vs taxol/carbo, randomized Phase II) initially looked positive for overall survival but subsequent analysis failed to show a benefit. The first poster described the results of a small study with only 25 patients who received Avastin plus an intermediate dose of inteferon-alfa. The combination appears active and the median PFS/OS were 4.9 months/18.4 months.

The second poster combined a slightly different Avastin dose with a modified Temdoar dose–Temodar is usually 150 mg/m^2 for five days every three week cycle but this study used that dose over 7 days every two weeks (?). The PFS and OS numbers from the 62 patients treated were fairly pedestrian (4.2 months/9.3 months) but BRAF V600E mutants had a longer OS (14.8 months). This reinforces the overall concept that melanoma patients and their therapies are probably best characterized and designed using specific tumor mutation information, the most prominent of which currently is the BRAF mutants (followed by c-KIT).

# 3:  Phase II evaluation of tremelimumab (Treme) combined with high-dose interferon alpha-2b (HDI) for metastatic melanoma.

This trial is also an early evaluation of a combination therapy, treated with interferon alfa-2b and tremelimumab, a cousin of ipi. Historically, ipi and “tremmie” were both developed by the same investigators as part of the same experiment (distinct clones of the same antibody) and separately licensed. Tremmie failed as part of an early Phase 3 study sponsored by Pfizer while BMS continued to pursue ipi, resulting in the trial presented June 6. In the 36 pts treated, the median PFS/OS was 6.4 months/15.9 months. There was the expected level and type of side effects. CRP (C-Reactive Protein) is a potential biomarker for response.

#4: A phase I/II trial of DTIC and dasatinib in metastatic melanoma

This is another early study of a combination therapy with standard chemotherapy, DTIC, along with dasatinib, which is a tyrosine kinase inhibitor approved for use in some leukemias. The specific question in this trial was the selective actions of dasatinib can increase the effectiveness of chemotherapy to treat melanoma. The 49 patients treated tolerated the drug combination fairly well and an MTD (maximally tolerated dose) was identified for dasatinib in this combo. This combo showed some, if not overwhelming, clinical activity, with a median PFS/OS profile of 3 months/8.5 months. I suspect that this data will be clarified and improved by mutational analysis of the tumor tissue. If this was already in the poster, I may have missed it due to time constraints.

#5:  Frequent dosing and GPNMB expression with CDX-011 (CR011-vcMMAE), an antibody-drug conjugate (ADC), in patients with advanced melanoma

I like this trial because it addresses “targeting” in a different way: as an antibody-drug conjugate, meaning that the melanoma cell is targeted by the agent because of an attached antibody to a surface protein, then once inside the cellular toxin is released. I’m not sure this is the perfect conjugate or how much further it will be pursued in melanoma, but it is broadly speaking a great concept for the future as our understanding of the melanoma cell and its variability improves.

Honorable mention:

Early FDG-PET responses to PLX4032 in BRAF-mutant advanced melanoma

If your tumor responds, can you assess that only by tumor size on scans or is tumor metabolic rate also important. This is an interesting look at patients treated with the thus far impressive PLX4032 BRAF inhibitor, comparing RECIST response to “metabolic” response. Interestingly, they didn’t correlate that well. Good food for thought.

Phase II trial of ipilimumab monotherapy in melanoma patients with brain metastases

The other honorable mention poster is mostly of interest because of the fanfare associated with ipi at this year’s ASCO. This study examined its effect on brain metastases. It had some activity (good) and was tolerable (also good). The extent of benefit was difficult to assess in this diverse but small patient group. This is important if ipi gets approved since in the past people have worried about the effect of immunotherapy on brain metastases, since immunotherapy can cause initial swelling which could be very harmful in the closed confines of the skull.

Eric D. Whitman, MD

Senior Editor


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