Oh, what a surprise! After pooling together data from six whole clinical trials conducted between the ancient times of January 2018 and the futuristic era of March 2023, researchers have stumbled upon a groundbreaking revelation in the treatment of high-risk resectable melanoma (HRRM). Brace yourselves: dual checkpoint inhibitors (DCPI) might just be more effective than anti-PD1 monotherapy. Who would’ve thought, right? But wait, there’s a catch – it also comes with a higher chance of making patients feel like they’ve been hit by a truck, thanks to those lovely grade 3 or 4 immune-related adverse events (irAEs).

Patients were treated with either the lonely anti-PD1 monotherapy; a tag team of DCPI with a “conventional” dose that sounds like it was decided by throwing darts at a board (3-mg/kg ipilimumab and 1-mg/kg nivolumab); or an “alternative” dose that probably involved flipping a coin (1-mg/kg ipilimumab and 3-mg/kg nivolumab).

The main outcomes measured were basically a series of acronyms that sound like rejected robot names from a sci-fi movie: rCR, rOOR, and pCR. And, of course, whether or not the patients could still undergo surgical resection without turning into a Marvel superhero from the side effects.

After analyzing data from 573 patients (because who needs a larger sample size when you’re having fun?), it turns out that DCPI is indeed more effective than sending patients into battle with anti-PD1 monotherapy alone. The odds of achieving a pathologic complete response (pCR) were like comparing the chances of finding a needle in a haystack versus finding a needle in a slightly smaller haystack. But, as the universe demands balance, DCPI also significantly increases your odds of experiencing irAEs that are about as pleasant as a surprise math test.

And for those who enjoy a bit of gambling with their treatment options, the study found no significant difference between playing darts or flipping coins to decide on the dosage of ipilimumab and nivolumab. However, if you’re into higher stakes, the conventional dose will give you better odds for improved responses but also a higher chance of feeling absolutely terrible.

In conclusion, this riveting episode of “Melanoma Treatment Roulette” reveals that while DCPI might help you win the battle against HRRM, it could also leave you feeling like you’ve gone a few rounds with a heavyweight boxer. And in the thrilling dosage showdown, it seems that more is not always better, except when it comes to the likelihood of adverse events. Remember, folks, in the world of medical research, no good deed (or treatment) goes unpunished.