‘Miracle’ drug stopped working, but lung cancer patient lives on

For Gail Sadler, who has quadrupled her expected survival time, clinical trial picked up where standard therapy left off.
June 14, 2021
“I hear ‘no’ and I’m like, ‘What? No is not an option,’” Sadler says. “Or ‘You’re gonna die.’ I don’t take that as an answer, either.” Photo by Cyrus McCrimmon for UCHealth.

Last time UCHealth Today wrote about Gail Sadler, the headline read, “She was given two years to live with lung cancer, max. That was four years ago.”

That was nearly four years ago.

To review: When diagnosed in December 2013 with stage 4 non-small cell lung cancer, Sadler, then 52, was given six months to two years to live. She went on chemotherapy (cisplatin first, then docetaxel) to address tumors in her left lung, left hip, right femur, vertebra, sternum, and throat. Chemotherapy helped until about a year after diagnosis. Then in December 2014, nivolumab (trade name Opdivo) was approved by the U.S. Food and Drug Administration.

Cancer spreads in part by chemically hiding itself from an immune system that would otherwise attack the malignant cells. Immunotherapies such as Opdivo work by poking holes in that chemical cloak so the immune system can take the fight to cancer and keep the disease in check. It doesn’t always work, but for Sadler, Opdivo was a revelation: The cancer disappeared, and she experienced no side effects.

But all the while her cancer was trying on countless molecular disguises. Ultimately it evolved into one that fooled even her Opdivo-enhanced immune system. In March 2020, shortly after Sadler moved from Littleton to Castle Pines and the COVID-19 pandemic hit, a tumor appeared on a lymph node on her neck. The woman who was perhaps one of the world’s longest-term Opdivo “customers” had relapsed. The FDA had approved Opdivo based on a clinical trial that found the drug to extend survival by about three months; Sadler had received 86 Opdivo infusions over more than five years.

Gail Sadler, a lung cancer patient, on the tarmac outside Modern Aviation where she works at Centennial Airport.
Gail Sadler on the tarmac outside Modern Aviation where she works at Centennial Airport. Sadler was given max two years to live – more than seven years ago. Photo by Cyrus McCrimmon for UCHealth.

What next for a stage 4 lung cancer patient?

Ten rounds of radiation therapy led by UCHealth and University of Colorado School of Medicine radiation oncologist Dr. Brain Kavanaugh eradicated the neck tumor. The question, though, was how to keep the rest of her cancer under control now that Opdivo was no longer doing its job. Not long ago, Sadler’s story would be coming to an end. But the last few years have brought a revolution to lung cancer treatment, and these life-extending innovations show no signs of slowing down.

Sadler undergoing radiation therapy for a lymph-node tumor.
Sadler prepares to undergo radiation therapy for a lymph-node tumor in March 2020. She was at that point the longest-surviving patient on Bristol Myers Squibb’s immunotherapy drug Opdivo. Photo courtesy of Gail Sadler.

Opdivo was the first new immunotherapy-based lung cancer drug when it was approved in late 2014. In the six-plus years since, multiple other immunotherapy drugs and targeted therapies have joined it in the lung cancer armamentarium – most recently at the end of May. Many of these drugs target the mutations of specific genes known to drive individual variants of non-small cell lung cancer – eight mutations now have a specific drug licensed for them. Dr. Ross Camidge, who leads lung cancer research at the CU School of Medicine and sees patients at UCHealth University of Colorado Hospital on the Anschutz Medical Campus, says those mutations account for more than half all non-small cell lung cancers (88% of lung cancers are NSCLCs, he adds). He expects the number of targeted genes to grow, he says.

“Not that we have an answer for everybody yet, but we are pulling bricks out of the wall one by one,” Camidge said.

The fruits of pharmaceutical progress are plain to see, he says.

“Last week in clinic, I had two patients who have been stage 4 for 10 years,” Camidge said. “We are creating long-term lung cancer. It used to be that you were either cured or had a short amount of time left.”

What’s interesting about Sadler’s case, Camidge says, is that she’s done so well despite her cancer not being attributable to a single mutated gene. She’s far from alone in having what he called a “committee” of cancer drivers. None of these remarkable new drugs, typically prescribed for people with specific mutations Sadler doesn’t have, were designed to help her. Opdivo isn’t gene-specific, and that it worked so well remains a mystery Camidge and colleagues in Colorado and around the world are still working to understand.

“Her immunotherapy can be given to almost anybody. It works amazingly well in 20% of people, but we don’t know who those 20% of people are,” Camidge said.

The issue isn’t the 20% of patients for whom Opdivo or other broad-based therapies mysteriously work; it’s the 80% for whom they don’t. They lose time as their cancer spreads. That uncertainty also hinders the scientific community’s ability to develop and prescribe drugs for subsets of patients whose lung cancers, like Sadler’s, probably have roots in multiple genetic and other factors. A year ago, Sadler and her UCHealth care team faced exactly this problem. Opdivo had failed and the roots of her cancer remained unexposed. What could they do for her?

Gail Sadler, a lung cancer patient, outside Modern Aviation at Centennial Airport.
Gail Sadler has done well despite her cancer not being attributable to a single mutated gene. Photo by Cyrus McCrimmon for UCHealth.

Lung cancer patients seek clinical trials

Sadler has for years received the vast majority of her medical care at UCHealth Lone Tree Medical Center – it’s close to home, which is no small matter given the roughly 100 appointments a year a late-stage cancer patient can expect. Dr. Regina Brown, and, more recently, Dr. Jose Pacheco, who also sees patients at the UCHealth Lung Cancer clinic – Anschutz Medical Campus, saw that clinical trials of promising cancer-drug candidates would be the path forward for Sadler. About 40% of UCHealth lung-cancer patients are on clinical trials, the highest percentage of any U.S. lung cancer center, according to Camidge.

“When immunotherapy stops working after it has clearly worked before, that’s likely a different issue than when it doesn’t work in the first place, said Camidge. “The behavior of the cancer tells you something about its underlying biology. It tips its hand a little,”

Pacheco and the lung cancer care team settled upon a clinical trial featuring a combination of two approved drugs: ramucirumab (trade name Cyramza) and pembrolizumab (trade name Keytruda). Keytruda works much like Opdivo; Cyramza would help Ketruda reestablish immune control. Sadler would take them through infusions every three weeks at UCHealth Lone Tree Medical Center. Pacheco, who is leading the trial’s implementation across the UCHealth network in Colorado, was particularly familiar with the potential of the combination.

Sadler has responded to the drug without side effects as of late May – more than a year into treatment. She has been working since March 2020 as a customer-service lead at Modern Aviation, which serves private-jet clients from Centennial Airport. Despite Sadler possessing a smile as wide as an aircraft’s wings and a personality and energy level seemingly fueled by some hidden turbine, she was pleasantly surprised by the job offer.

“Not everyone will hire someone with stage 4 lung cancer,” she said. “They took a chance on me.”

Sadler, a stage 4 lung cancer patient, with friend and Modern Aviation colleague Janet Gallagher.
Sadler with friend and Modern Aviation colleague Janet Gallagher. Gallagher and others at Modern Aviation “went out on a limb” when they hired her a year ago, Sadler says. “Not everyone will hire someone with stage 4 lung cancer.” Photo by Cyrus McCrimmon for UCHealth.

She insists on scheduling her infusions and other medical appointments on Fridays, one of her days off, so that she misses a minimal amount of time at work. She tips her hat to UCHealth for being able to work around her schedule.

There have been setbacks along the way. Most recently, on May 11 Sadler had three holes drilled into a femur that had probably fractured because prior radiation treatments had weakened it. But for years now, she has lived her life. She loves her job. She has cherished time with her daughter Shannon and granddaughter Ava; she experienced the wedding of son Cameron; and she was in San Diego 10 days after the femur surgery to join her daughter Alex, recently engaged, for some wedding-dress shopping. The wedding is scheduled for October 2022, and Sadler plans on being there.

“Nobody’s getting out alive – I mean, what the hell,” Sadler said. “But my fear of dying right now is like zero.”

Should the current trial’s drugs stop working, she’s confident that Pacheco will find her another option, she says.

“I’m in the best possible hands. I’ve always felt that way,” she said. “These people care. They dig in. They’re with you in this fight. You never feel like you’re a one-woman army.”

Those who know Sadler would argue that she’s a one-woman battalion at least. Certain is this: Whatever happens next, she’ll be up for the challenge.

About the author

Todd Neff has written hundreds of stories for University of Colorado Hospital and UCHealth. He covered science and the environment for the Daily Camera in Boulder, Colorado, and has taught narrative nonfiction at the University of Colorado, where he was a Ted Scripps Fellowship recipient in Environmental Journalism. He is author of “A Beard Cut Short,” a biography of a remarkable professor; “The Laser That’s Changing the World,” a history of lidar; and “From Jars to the Stars,” a history of Ball Aerospace.