Tuesday, July 7, 2015
PD-L1 positive? Which immunotherapy is best? Same song, second verse...
Differential activity Nivolumab, Pembrolizumab, and MPDL3280A according to the tumor expression of Programmed Death-Ligand (PD-L1): Sensitivity Analysis of trials in melanoma, lung, and genitourinary cancers. Carbognin, Pilotto, Milella, et al. PLos One. June 18, 2015.
The potential predictive role of PD-L1 expression on tumor cells in the context of solid tumor treated with checkpoint inhibitors targeting the PD-1 pathway represents an issue for clinical research. ORR was extracted from Phase I-III trials investigating nivolumab, pembrolizumab, MPDL3280A [an anti-PD-L1 product] for advanced melanoma, NSCLC, and genitourinary cancer... Interaction test according to tumor PD-L1 was accomplished, and analysis performed. Twenty trials (1,475 patients) were used. A significant interaction per tumor PD-L1 expression was found in the overall sample with an ORR of 34.1% in the PD-L1 positive and 19.9% in the PD-L1 negative population. ORR was significantly higher in PD-L1 positive in comparison to PD-L1 negative patients for nivo and pembro, with an absolute difference of 16.4% and 19.5% respectively. A significant difference in activity of 22.8% and 8.7% according to PD-L1 was found for melanoma and NSCLS, respectively with no difference for gu cancer. Overall, 3 antibodies provide a significant differential effect in terms of activity according to PD-L1 expression on tumor cells. The predictive value of PD-L1 on tumor cells seems more robust for anti-PD-1 antibody (nivo and pembro) and in the context of melanoma and NSCLC.
1. Background info on MPDL3280A: Anti-PD-L1 for melanoma phase 1 trial
2. Note that you can still respond, even if PD-L1 negative. Is that true? Does that reflect action of the medication? Or, is the current test for PD-L1 not terribly accurate?
3. Let's standardize testing tumors for the presence of PD-L1 and make it available to all melanoma and NSCLC patients so treatments can be chosen more wisely!!! NOW!!! Prior rant on my tumor testing for PD-L1: Info on test for PD-L1 from 2012!
4. I think we ratties have given you enough intel over many years. Researchers and FDA weirdo's...get with it! Make this happen, TODAY!!!
Don't make me come back there! c