Adam Feuerstein/STAT

Immunotherapy

Keytruda shows benefit in early stage lung cancer

The use of Keytruda before and after surgery in people with early stage lung cancer reduced the risk of relapse, disease progression, or death by 42% compared to placebo in a large clinical trial, its maker Merck and researchers reported Saturday. 

The findings from the Merck study called KEYNOTE-671 provide more evidence to support using immunotherapy drugs in earlier stages of lung cancer — first to shrink tumors to improve surgical outcomes, and then post-operatively to eliminate residual tumor cells. Earlier and prolonged use of Keytruda or other similar checkpoint inhibitors in the so-called perioperative setting could also add billions of dollars in sales to what are already blockbuster commercial products. 

Earlier this year, AstraZeneca reported positive results from a perioperative lung cancer study of its checkpoint inhibitor Imfinzi.

The KEYNOTE-671 study results were presented by Heather Wakelee, a medical oncologist at Stanford Medicine. The data were published simultaneously in the New England Journal of Medicine. The outcome is meaningful, she said, because more than half of patients with early stage lung cancer that is surgically removed still experience relapse that requires further treatment. 

She also noted that patients will only benefit from perioperative immunotherapy if lung cancer is detected early, before it becomes inoperable or spreads to other parts of the body. “We need to push for more screening,” she said.

During a discussion session, Mark Awad, a medical oncologist at Dana-Farber Cancer Institute, said KEYNOTE-671 and other perioperative immunotherapy studies were a “major advance” and could be a new standard of care. Longer follow up is needed to determine if this strategy will prolong survival, he said, and further studies should be done to more precisely measure the additive benefit of postoperative immunotherapy when it’s used before surgery.

The Food and Drug Administration is reviewing Merck’s application for perioperative use of Keytruda in lung cancer, with a decision expected by Oct. 16. 

Coffee and cigs

A culinary report from the exhibit floor

The ASCO meeting is a great place to see important clinical data. But attending is also a reminder that medicine is very much a commercial enterprise – especially when a reporter is walking the cavernous exhibit floor. Here, you'll find enormous, glowing drug company sales booths, many topped with flying saucer-like signs emblazoned with AstraZeneca, Pfizer, and Bristol-Myers Squibb.

Of course, one of the main currencies in any sales effort is free food. Booths offering made-to-order lattes drew caffeine-starved crowds. Eisai was set up to serve iced tea and veggie dumplings. Novartis had chocolate lava cakes. Myriad Genetics, in a small booth off to the side, was handing out cups of Dippin’ Dots, the candy covered ice cream snack.

But beneath the exhibit floor was also an unfortunate reminder of why cancer research, and meetings like this one, are necessary: An emergency exit stairwell apparently used by workers taking smoke breaks, littered with cigarette butts, some still smoldering. 

Lung cancer

The ups and downs of TIGIT

You’ll be forgiven for losing track of the ever-shifting sentiment around anti-TIGIT immunotherapy. These experimental antibodies are designed to kill cancer cells by unleashing the brakes of the immune system while also stepping on the gas. But data reported so far have provided few definitive answers about TIGIT’s future, particularly in lung cancer. 

An update today from a mid-stage study of domvanalimab, an experimental, anti-TIGIT therapy from Gilead Sciences and Arcus Biosciences, didn’t offer clarity. The addition of domvanalimab to another experimental drug called zimberelimab PD-1 — the “dom-zim doublet” — reduced the risk of tumor progression by 33% compared to zim on its own. 

The benefits shown by the dom-zim doublet were consistent with an update last December and “supports the potential therapeutic benefit of inhibiting the TIGIT pathway,” said Melissa Johnson, a lung cancer specialist at the Sarah Cannon Research Institute, speaking to a large crowd Saturday. 

But when Johnson reported on the same study last December, the dom-zim doublet reduced the risk of tumor progression by 45%. The benefit shown today narrowed with longer follow and also dropped outside the encouraging embrace of statistical significance. 

“These results reinforce the data we saw in December with longer follow-up,” said Bill Grossman, senior vice president and therapeutic head of Gilead’s oncology unit. 

Gilead and Arcus are conducting Phase 3, randomized clinical trials of domvanalimab in lung cancer. Patient enrollment is still underway, but today’s data “supports confidence” in the program, Grossman added.

Questions still swirl around TIGIT’s role in treating lung cancer, but answers could come relatively soon when Roche reports an overall survival analysis from a Phase 3 study involving its own TIGIT compound called tiragolumab.