The National Cancer Institute Lung-MAP trial launched in 2014 was designed to accelerate clinical trials by allowing physicians to incorporate new drugs and combinations into rapid turn-around formats to study novel approaches for recurrent disease.
I applaud anything that accelerates clinical development, but once again the focus is almost exclusively genomic. A recent example used PDL1 stratification to craft a non-chemotherapy treatment consisting of the immune checkpoint inhibitor pembrolizumab (anti-PD1) with the anti-blood vessel antibody ramucirumab (anti-VEGFR).
The study reported at the 2022 American Society of Clinical Oncology, randomized patients to physicians-choice of treatments versus the experimental ramucirumab plus pembrolizumab arm.
Touted as an important breakthrough, even practice-changing by some, the actual results are a bit less compelling.
The study did not reveal a progression-free survival difference.
While it had an approximate 3-month overall survival improvement that achieved statistical significance by log-rank p=0.05 this wasn’t confirmed by weighted log-rank.
More to the point, the comparator arm chosen by the physicians used docetaxel plus pembrolizumab as well as a smattering of single-agent drugs with some patients receiving no treatment at all.
Whatever the marginal benefits, the report did not include financial toxicity. The current list price of ramucirumab is in the range of $14,000 to $15,000 per month and that of pembrolizumab is $10,000 per dose. When we add these together we have a treatment with a monthly cost approaching $20,000 to $30,000 per patient.
On an annualized basis, that would be $240,000 to $360,000. But when we then consider that the overall survival advantage was three months, the cost to achieve one quality life year (QALY), a standard measure of cancer therapy effectiveness, is much higher still.
Although cooler heads prevailed and most suggested this wasn’t practice-changing, it is alarming that such marginal improvements at such extremely high costs could possibly constitute a new direction in cancer medicine.
Had the patients in the physician’s choice arm instead been offered a more active and appealing control arm of drug response profiling, with their tumor tissue used to select therapy, the dual antibody treatment would likely have been bested and retired hastily.
We need to move away from exclusively genomic trials toward more biologically relevant endpoints. The current Lung-MAP is just the most recent iteration of gene-driven studies that are driving our patients in the wrong direction.