“My name is T-Cell…, James T-Cell”
Immune T-cells are licensed to kill other cells through a quick molecular kiss of death, and as such are potentially powerful allies in controlling a tumor. For obvious reasons this killing power is under strict regulatory control and in particular T-cells display PD-1 proteins on their surface, which when engaged by the ligand PD-L1 on another cell, protects that cell from being killed. Tumors often display high levels of PD-L1 so that disrupting the interaction between PD-L1 and PD-1 can enhance the effectiveness of immune killing of tumor cells. Amplifying results from last year in lung cancer, the antibody against PD-L1 pembrolizumab (Keytruda, Merck) was shown to be greatly superior to standard chemotherapy in first line treatment for patients selected on the basis of lung tumor expression of PD-L1 (about 30% of lung cancers). Similarly the antibody against PD-1 nivolumab (Opdivo, BMS) was shown to have significant survival benefit (doubling of survival at 1 year from 20% to 40%) in patients with terminal head & neck cancers, with the benefit highly concentrated in the set of patients whose tumors expressed PD-L1. Unfortunately, these drugs can also kill, as attested by a case report of a couple of unfortunate patients whose unleashed immune systems turned against their heart. Pembrolizumab versus Chemotherapy for PD-L1–Positive Non–Small-Cell Lung Cancer; Nivolumab for Recurrent Squamous-Cell Carcinoma of the Head and Neck; Fulminant Myocarditis with Combination Immune Checkpoint Blockade (subscriber access)
It’s not only about immune-oncology, Cyclin D kinase inhibitors are coming of age too
Last year, FDA approved palbociclib (Ibrance, Pfizer) as a breakthrough therapy for hormonally responsive advanced breast cancer on the basis of early clinical data and pending confirmation through phase 3 studies. Similarly FDA gave breakthrough designation to two other drugs (ribociclib – Novartis, and amebaciclib – Lilly) with the same target. This is now vindicated with several studies showing a large progression free survival benefit in this patient population. And this is only the tip of iceberg as cyclins are ubiquitous actors in the control of the cell cycle of replication (hence the name). A quick check on clinicaltrials.gov shows that currently there are 122 open trials between these three drugs; the competition for investigators and patients must be fierce. Ribociclib as First-Line Therapy for HR-Positive, Advanced Breast Cancer; Palbociclib and Letrozole in Advanced Breast Cancer; A New Cell-Cycle Target in Cancer — Inhibiting Cyclin D–Dependent Kinases 4 and 6; CDK4 and CDK6 Inhibition in Breast Cancer — A New Standard (subscriber access)
Meanwhile, in our dysfunctional health system…
Anecdotes about patients being stung by out-of-network charges while getting care at a hospital abound – the surgeon was in network but not the anesthesiologist, the OB was in network but not the maternal fetal medicine specialist etc., but the phenomenon has not truly been quantified. Now an analysis of a large commercial claim dataset shows that more than 1 in 5 emergency department visits to in-network hospitals result in bills from ED physicians that are out-of-network. The problem is not only that this is not covered by insurance, but that what is charged is at “the list price” which is essentially an opening bid for negotiation with payers and is typically several-fold higher than the customary price. The authors don’t say this but through a back on the envelope calculation, it is apparent that on average this must improve ED physician incomes by at least 20%. The solution is simple and regulatory (which given the current political mood may be long in coming), requiring network rates for all services that are accessed at a facility that is in network. Out-of-Network Emergency-Physician Bills — An Unwelcome Surprise (subscriber access)
The New England Journal of Medicine is a premier weekly medical journal covering many topics of interest to the health sector. In this monthly series we offer an opinionated perspective on selected highlights that might be of interest to our clients and others.