Attempts to give immunotherapy through insurance authorization by exemption or enrollment in clinical trials will often come with delays in treatment. Patients may be ineligible for several of the agents that are required before pembrolizumab. For example, in gastric cancer, single agent pembrolizumab is approved in locally advanced or metastatic gastric or GEJ adenocarcinoma in tumors that express PD-L1 with disease progression on or after 2 or more prior lines of therapy including fluoropyrimidine- and platinum-containing chemotherapy and if appropriate HER2/neu-targeted therapy (Keytruda. Third, pembrolizumab is approved with requirement of prior line therapy or expression of biomarkers in certain cancers. In the current system, some patients would never practically be eligible for checkpoint inhibitors, thus missing the opportunity to benefit from a potentially durable response. Lack of PD-L1 expression in tumors, as in non-TMB-high tumors does not preclude response and some excluded patients may even achieve complete or long-term response.
2020), even in non-TBM high patients with rare cancers 2% achieved complete response some of whom may have long-term remission.
Keynote 158 clinical trials.gov trial#
Patients with rare tumor types and who are also negative for known predictive biomarkers however are unlikely to find a trial dedicated to that subgroup. Currently, there are 164 KEYNOTE studies searchable in website. Therefore, many patients without an approved indication must wait for individual studies of each tumor type before being able to try pembrolizumab. There is limited understanding of the predictors of response to immunotherapy except in certain tumors such as NSCLC where PD-L1 is a strong predictive biomarker. Second, patient otherwise ineligible for immune checkpoint inhibitors would have the opportunity to be treated. Based on these observation, we estimate that among all real-world patients 8.3% will respond to checkpoint inhibitors based on current FDA labels. Trial eligible patients had a response rate of 47% compared to 36% in trial ineligible patients. 2021) patients with renal cell carcinoma (RCC), non-small cell lung cancer (NSCLC) and melanoma had different response rates based on trial eligibility based on performance states, baseline labs and presence of brain metastases. A study of real-world outcomes of patients with solid tumor malignancies by Gan et al. This estimate was updated to approximately 36.1% eligible patients and 10.9% response rate in 2019 due to negative confirmatory trials (Haslam et al. This is based on response rates in FDA drug labels from clinical trial patients. have reported that approximately 43.63% of US patients with metastatic cancer were eligible for checkpoint inhibitors in 2018 and approximately 12.46% might achieve a response (Haslam and Prasad 2019). Based on FDA drug approvals, Haslam et al. Randomized clinical trials should focus more on optimal duration of treatment based on tumor type and initial response to checkpoint inhibitors.įirst, treatment outcomes may be similar. We conclude that giving pembrolizumab in any metastatic solid tumor in any setting may lead to better outcomes with minimal increase in cost. The current regulatory framework of numerous overlapping clinical trials leading to complex approval indications is redundant and inefficient. Due to heterogeneity of response to checkpoint inhibitors and limited predictive biomarkers, there are subsets of patients without approved indications for pembrolizumab that may have response to checkpoint inhibitors. The aggregate response rate in landmark clinical trials for approved indications of pembrolizumab is low and even lower in real-world populations. Here we argue that allowing the use of pembrolizumab to any advanced solid tumor in any tumor type in any line of therapy for a fixed duration may be preferable to the current assortment of indications. The current approval indications for pembrolizumab are complex, reflecting the inclusion criteria of numerous clinical trials that led to approvals.
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