The PINCH study
The PINCH study was designed to investigate PD-L1 PET imaging, a new technique to predict response to immune therapy in patients with recurrent or metastatic head and neck cancer. This technique potentially visualizes tumor cells expressing the protein PD-L1. The number of visualized tumor cells will be correlated to the treatment response with durvalumab.
Head and neck cancer is the sixth most common cancer worldwide, with an overall survival rate of 65% after 5 years. In attempts to improve survival, immune therapies targeting PD-L1 have been studied extensively, resulting in impressive and durable antitumor responses. However, only 15-20% of patients respond to these drugs. This means that non-responders are exposed to expensive, ineffective treatment, and its associated side effects, while alternative treatment is delayed. Therefore, there is an urgent need for a predictive biomarker to select patients who could benefit from immune therapy.
Patients with recurrent or metastatic head and neck cancer were approached to participate in the PINCH study, offering one PD-L1 PET scan before treatment with the anti PD-L1 checkpoint inhibitor durvalumab. The PD-L1 PET scan can visualize tumor cells that express a protein referred to as PD-L1. Based on previous studies, the presence of tumor cells expressing PD-L1 can predict the response to treatment. Currently, the presence of PD-L1 is analyzed on a sample of tumor tissue. This sample does not reflect the presence of PD-L1 on all tumor cells, therefore this can lead to misinterpretation. PD-L1 PET-imaging can overcome these limitations. It visualizes PD-L1 positive tumor cells throughout the whole body with a high specificity, avoiding sampling errors and misinterpretations.
If the visualization of PD-L1 positive tumor lesions is feasible, this technique can be extended in a prospective trial to study the potential value of PD-L1 PET-imaging as a predictor for treatment with immune checkpoint inhibitors by correlating the tracer-uptake with the response to treatment.
At the end of the trial we concluded that PD-L1 PET-imaging with 89Zr-labeled durvalumab is feasible and safe. However, in this small subset of patients the uptake of 89Zr-durvalumab did not correlate to PD-L1 expression on a patient level and could not predict durvalumab response.
We also evaluated the correlation between tumor metabolism and ICI response, as performed in previous studies. Our data suggests that particularly [18F]FDG total lesion glycolysis may identify poor durvalumab responders upfront. A potential explanation could be that patients with more extensive disease have already undergone extra steps in the immune escape route.
Despite the fact that [89Zr]Zr-DFO-durvalumab did not correlate to treatment outcome, we do see potential of 89Zr-labeled antibodies in optimizing the ICI treatment efficacy in patients with R/M SCCHN 40. Besides an unique insight in antibody biodistribution, the in vivo visualization of 89Zr-labeled antibodies highlights essential local effector mechanisms, reveals the complexity of dose-response relations, and may shed a new light on the role of non-tumor located PD-L1 expression in the anti-cancer immune responses 39. Ultimately, this teaches us how to use (and combine) these drugs to improve response rates; an essential step in early drug development suitable for phase 1 and 2 clinical trials.
