When 2018 began, there was still plenty of uncertainty surrounding the previously untreated lung cancer market—the holy grail for immuno-oncology drugmakers, thanks to its sheer size.

Merck had the lead with two approvals for Keytruda, but three other companies were awaiting combo data and aiming to take the crown. Doubts were also swirling among investors that Merck could replicate the phase 2 success for its own combo—a Keytruda-chemo pairing—in a confirmatory phase 3 study.

Let’s just say the picture doesn’t look that way anymore. When 2019 kicks off, Merck's dominance will be pretty clear.

As Evaluate’s Vantage put it in a recent report, "the year that started with the promise of a first-line lung cancer shakeout" will leave Keytruda, "the drug that started in pole position, even more entrenched than before."

Concerns about Merck’s star didn’t persist far into 2018, with the New Jersey drugmaker announcing in mid-January that its chemo combo study had hit its primary endpoints. And Keytruda never looked back. It cut the death rate by half in that study, regardless of patients’ PD-L1 biomarker status, raising the bar much higher for its competitors.

It didn’t stop there, either. It trumped Roche’s win in squamous lung cancer with a bigger one of its own, and it put up monotherapy data to back Keytruda’s use in PD-L1-positive patients who can’t tolerate chemo. It overtook archrival Opdivo from Bristol-Myers Squibb in the sales department. And in the process, it might just have helped secure Merck CEO Ken Frazier some bonus years on the job.

Of course, Merck had some help. Its rivals have faltered, faced delays and made decisions analysts say could hurt their ability to challenge Keytruda down the line.

Bristol-Myers Squibb, for starters, built a key phase 3 study and FDA filing for its Opdivo-Yervoy combo around an unproven biomarker, tumor mutational burden (TMB); a new analysis of that data may actually have skewered the company’s plans for a timely first-line entry. Roche—which also went the chemo-combo route with its PD-L1 inhibitor Tecentriq—threw older blockbuster Avastin into the mix, meaning it’ll take on the Keytruda pairing with a cocktail that’s more expensive and potentially more toxic. And AstraZeneca’s Imfinzi-tremelimumab duo straight-up failed critical phase 3 trial Mystic.

That’s not to say there’s no opening left for any of Keytruda’s rivals. As analysts pointed out in June, the monotherapy win Keytruda posted at ASCO—results that’ll help dictate treatment for chemo-ineligible patients who can’t take Merck’s combo—was carried mainly by high PD-L1 expressers. "The fact that KN-042 was not overwhelmingly positive in patients with PD-L1 levels of 1-49% leaves that population potentially more available to better combination therapy approaches in the future," Credit Suisse analyst Vamil Divan wrote to clients at the time.

And the drug will get its first taste of first-line competition heading into next year, what with the FDA’s recent green light for Roche’s Tecentriq-Avastin-chemo trio.

Still, "Keytruda has left rival checkpoint blockers fighting over what is at best a vanishingly small slice of the pie," the Vantage report noted.

Of course, Keytruda’s success hasn’t been confined to lung cancer—and it won’t be in 2019, either. The drug already has investors at Bristol-Myers Squibb quaking in their boots over the prospect of a speedy kidney cancer approval that could diminish Opdivo’s market share. And as the drug advances in other tumor types, shareholders could punish Merck’s rivals, too.

All of that said, anyone expecting a dull year in which Merck runs away with the I-O market clearly hasn’t spent much time following the sector.

"If anything is certain about immuno-oncology, it is that nothing is certain," analyst Tim Anderson, then with Bernstein, wrote to clients in April.