Let the kidney cancer battle begin.

In this corner, weighing in at a market cap around $100 billion, is Bristol-Myers Squibb (BMY -0.30%) and its immunotherapy drug Opdivo.

And in this corner, weighing in at a mere $1.3 billion, is Exelixis (EXEL 1.84%) and its kinase inhibitor Cometriq.

Now go to your corners, and at the sound of the bell, come out fighting.

Fighting Novartis' (NVS 2.27%) Afinitor, that is.

At European Cancer Congress, both companies presented data for their trials comparing their drugs to Afinitor.

While a head-to-head comparison would obviously be most ideal, a comparison against the same active comparator at the same stage of disease progression -- in this case, after patients had failed an initial treatment, which is when Afinitor would normally be used -- is the next best thing.

It's clear both drugs are better than Afinitor, but Bristol-Myers Squibb's Opodivo clearly has Exelixis' Cometriq beat -- at least for now.

The problem for Exelixis is that it didn't run quite as big of a clinical trial as Bristol-Myers Squibb and started later. So while the larger pharma was able to show that its drug had a survival benefit compared to Afinitor, Exelixis was only able to show that Cometriq delayed the progression of the tumor.

There was a survival trend in favor of Cometriq, but it wasn't statistically significant. Exelixis' trial is continuing, but even if Exelixis ultimately proves that Cometriq can produce a survival benefit similar to Opdivo's 5.4 months longer than Afinitor, the biotech still as an uphill battle ahead of itself because Opdivo is clearly safer.

Cometriq produced serious adverse events in 40% of the patients, similar to the 43% seen with Afinitor. By contrast, in Bristol-Myers Squibb's head-to-head trial, only 19% of the patients taking Opdivo had serious adverse events, compared with 37% for patients receiving Afinitor.

Exelixis can overcome the adverse event issue if overall survival is substantially better than Opdivo; most patients would trade high blood pressure, gastrointestinal issues, and fatigue for a few extra months of survival. The adverse events can also be mitigated by reducing the dose.

Winner takes all (loser takes most)
We won't know which drug has won until they're approved for kidney cancer, but that seems like a foregone conclusion, given the data and that both drugs are already approved to treat other cancers.

Doctors could use Opdivo off-label before it's approved since it's already available to treat melanoma. Insurers would need to cover the off-label use, but since they'd have to pay for Afinitor anyway, coverage should be fairly easy to get once the compendiums that list doctors' best practices are updated.

Exelixis changed the formulation of Cometriq from a capsule to a tablet when testing the drug for kidney cancer, so it isn't clear that doctors could use the capsule, which is approved for thyroid cancer, off label to treat kidney cancer.

Given the potential head start in being able to treat kidney cancer patients, and the overall survival benefit, Bristol-Myers Squibb will probably capture nearly all of the second-line patients. Unless Cometriq produces an overall survival benefit over Afinitor that's substantially more than 5.4 months, Opdivo will remain in the lead position.

But Opdivo isn't a cure, so most of the patients are going to need another treatment. Some might be too sick for another treatment, but there will still be plenty of patients available to treat. And with a survival benefit over Afinitor, Exelixis shouldn't have too much problem getting used as the next drug in the treatment regimen.

If you can't beat 'em, join 'em
While Cometriq may never move ahead of Opdivo in the treatment paradigm, it's possible that the two drugs might get used together, potentially as a first-line treatment where even more patients are available. There's some evidence that Cometriq may make tumors more amenable to the immune system, which Opdivo boosts.

A phase 1 trial testing the combination is already under way, so we should know shortly if there's a possibility for this boxing match to turn into tag-team wrestling.