There are a number of CheckMate trials going on both in Britain and Globally. It’s obviously a wonderful soundbite, but is the double immunotherapy delivering? Here we look at lung cancer and mesothelioma.
Immunotherapy vs chemotherapy in lung cancer
For example, ‘First line Nivolumab (a PD-1 immunotherapy), plus ipilimumab (a PD-L1 immunotherapy) has shown improved overall survival in patients with advanced non-small-cell lung cancer (NSCLC)' (1). But the word checkmate surely means more than simply beating the previously used drugs, so the researchers have gone on to use two platinum based chemotherapy drugs as well for two rounds with the immunotherapy drugs, or four rounds alone. So, two immunotherapy drugs plus 2 chemo drugs vs just the two chemo drugs.
This was in a Phase III trial in 103 Hospitals in 19 countries; 1107 patients. Serious stuff. Median survival went to 14.1 months from 10.7 months. Being a chess player, I’m not sure that qualifies for the term ‘Checkmate’.
To be fair, I have now reviewed the data after a three year follow up, as well (2). I quote the Conclusions in the study: With a 3-year minimum follow-up, nivolumab plus ipilimumab with two cycles of chemotherapy continued to have long-term, durable efficacy versus chemotherapy alone; a manageable safety profile; and survival benefit in patients with or without baseline brain metastases or select somatic mutations, further supporting the regimen as first-line treatment for patients with metastatic NSCLC.
Double immunotherapy and side-effects
Now the reason I have had a little look at this is that I have been helping two people who were both on the same two immunotherapy drugs, and they both had to stop after 3 rounds because they had severe liver problems. Severe as in 2 months on Prednisolone and they are still in serious trouble. One has NSCLC and the other Mesothelioma. They both talked to me in the last 10 days. Curiously their oncologists told them they didn’t really understand why these men had reacted so badly, and that in each case, their patient was the only example he had come across.
Maybe it is just a coincidence?
Then I opened my mail today to find a third patient (NSCLC) in exactly the same state. Again told he was the only person it has happened to. He was taking no supplements.
Notwithstanding that I think most oncologists in the UK don’t know how to use an immunotherapy properly by preparing the patient’s gut (you can see what I wrote about making PD-1 work better, here), I was worried about these men so I checked side-effects.
In the study I reference above, hepatitis was just one of the problems; kidney failure led the way. And interestingly under side-effects was death - about 7 people in this study.
So, 0.7% of people taking these two immunotherapy drugs die. That certainly is Check Mate.
But hang on. 0.7% is roughly the same number of people who die overall having caught Covid, and much higher than people dying from Covid under 50. So why is this a big deal when it comes to Covid-19 vaccines, but not when you simultaneously take two immunotherapy drugs?
Double Immunotherapy and Mesotheloioma
Interestingly, the Checkmate 743 study (3) used the same two immunotherapy drugs for patients with non-resectable Mesothelioma. This was a straight, double immunotherapy vs normal chemotherapy trial. Again I quote from the conclusions: With a median follow-up of 43.1 months, nivolumab plus ipilimumab continued to prolong Overall Survival versus chemotherapy alone. Median OS was 18.1 versus 14.1 months and 3-year OS rates were 23% versus 15%, respectively.
Go to: Transarterial chemoperfusion give some hope to mesothelioma patients
*****
References
- First-line nivolumab plus ipilimumab combined with two cycles of chemotherapy in patients with non-small-cell lung cancer; Luis G. Paz-Ares et al; Lancet Oncol, 2021 Feb;22(2):198-211.
- First-Line Nivolumab Plus Ipilimumab With Chemotherapy Versus Chemotherapy Alone for Metastatic NSCLC in CheckMate 9LA: 3-Year Clinical Update; Luis G. Paz-Ares et al; Journal of Thoracic Oncology; NON-SMALL CELL LUNG CANCER, Volume 18, Issue 2, p204-222 February 2023
- First-line nivolumab plus ipilimumab versus chemotherapy in patients with unresectable malignant pleural mesothelioma: S. Peters et al; Ann Oncol, 2022 May;33(5):488-499.