Novel clinical trial shows promise, offers new options to treat lung cancer
The wedding day in Charleston dawned cold and windy. It didn’t matter to the best man, Kerry Hardy, though. He wasn’t supposed to be alive to see the day anyway. The day was a gift, and as fate would have it, just 15 minutes before the ceremony, the clouds parted and the strong winds settled.
The sky dissolved into the colors of a beautiful sunset as the bride and groom exchanged vows. It’s a moment Hardy will never forget, especially since many doctors expected the 54 year-old to have succumbed to non-small cell lung cancer long before February 18, the day of his oldest son’s wedding.Diagnosed with stage 4 lung cancer in 2015, Hardy knew the weather and his presence were both miracles. The father of four boys lives with his wife Beth in Augusta, Georgia, and is close to all his children.
“I know the trend is going away from Dad being the best man. But Rhodes asked me and pointed out to me that I was the only person that had been there for every important thing he'd ever done. After crying, I accepted with honor. I was so happy to be with him on the biggest day of his life.”Not only was Hardy there, he was able to deliver a speech with his usual quick wit and down-home style of humor that had his wife rolling her eyes and, by the end, everyone tearing up. Hardy’s quick to explain he’s a man of faith and not afraid of dying. He believes in fighting to be there for his kids, though, so he can experience as many special moments as he can.
A big reason Hardy was able to be at his son's wedding was his great response to an immunotherapy clinical trial. As immunotherapy continues to transform the cancer landscape, more of these miracles are happening. Hardy, who enrolled in the trial at Hollings Cancer Center (HCC) at the Medical University of South Carolina in 2016, knows he’s lucky because while immunotherapy treatment works for some, it doesn’t for others. There are many factors that come into play, including the type of cancer and the genetic mutations a person has.
A specialist in lung cancer, John Wrangle, M.D., knows the statistics. Lung cancer is diagnosed far more often than other cancers in the state, and it takes more lives. The rate of deaths from lungs cancer is more than three times the level of the next most-common cancer, colorectal.
“It’s exhausting to give bad news all the time,” Wrangle said. He and colleague Mark Rubinstein, Ph.D., teamed up to develop this trial in the hopes they could give lung cancer patients, often diagnosed at later stages of cancer, more options. Wrangle didn’t sleep the night before the trial’s first patient received the drugs. They had never been administered this combination of a checkpoint drug, nivolumab, with a new and powerful immune stimulation drug, ALT-803. The side effects were unknown.Hardy had a tumor the size of a lemon in his lungs. “When you have someone who has a tumor with molecular characteristics like his, you have close to zero expectation that immunotherapy is going to work for it,” he said, adding that he admired how Hardy was in for the fight.
“He was one of the most positive dudes I have ever met. He’s an ebullient character. He always makes it his mission to make everyone around him smile. What a wonderful response to being in a predicament that no one wants.”
The DiagnosisWhen Hardy was diagnosed with stage 4 cancer in 2015, he was 51 with four boys, his youngest a three-year-old toddler. “You can imagine. It was a shock,” he said.
Hardy, who never smoked, had had a couple bouts of pneumonia. His doctor said he was too healthy to be having so many infections and wanted him to get checked out. Fortunately, even though nothing was found from scans at one hospital, Hardy had the scans done elsewhere. This time, doctors found a cloudy spot on his lung. After getting a needle biopsy in September 2015, he returned to see a local oncologist, asking to get the results without any sugar coating.“I’m one of those people who wants to know it straight. I want to know what I’m dealing with.” Hardy got what he asked for. “She said, ‘If everything goes well, you may have about two years to live, at the most, with what you have. We don’t see this as having a long-term survival rate.’”
Hardy, who teaches first aid and CPR classes and owns a custom closet business, took it in stride. “I didn’t give up. We had our cry and our big one-day pity party. I said let’s do this today and get it over with and then let’s go fight.”The research and phone calls started to find the best course of treatment. He put out several feelers and following up on a lead from a doctor in Miami, Florida, ended up at HCC, consulting with surgeon Chadrick Denlinger, M.D., and Wrangle.
“It was a little bit of a windy road to get to Charleston, but we realized it was where we were meant to be. That’s all divine stuff. I’m a religious guy, so I believe in all that.”His surgery was scheduled in October 2015. Doctors were hoping the big tumor in his upper left lobe was the extent of his cancer. “As they started surgery, though, they realized other tiny areas that had shown up on scans were also cancerous. They basically closed me up and we started talking to Dr. Wrangle.”
The only option for him at that point was chemotherapy, which worked for six months and then stopped working, which is what the doctors expected given the kind of cancer he had. “That wasn’t a big shock to us. When the chemo stopped working, my tumor doubled in size and that’s when Dr. Wrangle had just been approved for that new clinical trial.”Hardy knew he’d be one of the first people to get this treatment and that he didn’t have many options. Waiting for the results of a scan after the first round of treatment was nerve-wracking for everyone, he said.
“When we got the first results, we cried. All of us did.” He said Wrangle had warned him that most patients with his type of cancer do not respond to immunotherapy and that he didn’t want to offer false hope. “Dr. Wrangle was ecstatic. He had had some doctors say it wouldn’t work on me. We always had hoped, of course, that the cancer would go away. We knew that wasn’t the reality, though, so we hoped for longevity – that I could live for a long time stable until the next magic bullet comes along.”Hardy, who saw an almost 30 percent decrease in the size of his tumor, has been stable for two years. He is worried about what will happen when he comes off the trial and stops treatment, but he knows Wrangle has something in mind. “The longer you live – the more magic bullets that get introduced into the market. That’s what’s happening now with all these immunotherapies that are getting developed,” he said.
He takes it a day at a time. “To say I’m ecstatic is an understatement. I’m on the way now to South Georgia to teach CPR and first aid. If you could see me, you’d never know that I have been sick.”
Wrangle wishes he could see those results with all his patients and is thankful for the ones who do respond as well as Hardy. The results of the trial were recently published in
The Lancet Oncology.
In the early Phase 1b trial, there were nine patients of 21 treated who had positive responses with their conditions stabilizing and some experiencing a decrease in tumor size. Of the 21 patients, 11 had previously received immunotherapy that had stopped working. Several of these patients’ tumors shrank again with the addition of ALT-803 to a failing immune-checkpoint therapy. Wrangle said it’s these cases that keep him and his colleague, Mark Rubinstein, Ph.D., pushing forward.“Observing people who are meeting all kinds of milestones and seeing incredible kinds of things happen in their life that they otherwise wouldn’t have gotten to enjoy and participate in, that’s 100 percent what it’s all about,” Wrangle said. The trial was designed to be delivered in an outpatient setting, and he’s encouraged to see that the treatment seems to be well-tolerated. “We design these therapies so these people can get on with living their lives, not so they can be cancer patients forever and ever.”
Only time will tell if this therapy will bear out in more advanced trials, he said. It’s important to get funding so researchers can keep exploring immunotherapy advances that show great promise. The next phase for him and Rubinstein will be to will be explore different dosing schedules and further define the mechanisms behind the differences in patients’ responses.“There’s a lot of work to do with the science to find out who does respond and who doesn’t.
“Will we cure all cancers? Probably not in my lifetime. Will we cure some solid tumor cancers that were previously considered incurable? Yes, there are some people for whom that is going to happen.”Wrangle cautions patients to not lump all cancers together as one entity and that not even all lung cancers can be seen as one group given genetic variations among the tumors. Each case needs a tailored approach. “Our therapy won’t work for everyone, but we desperately want to find out for whom it will work. Will it be a cure? It’s possible, but for a select few. Some won’t be cured but will be alive for years and years just because we’re able to stabilize the disease or reach equilibrium between the immune system and the tumor.”
When that miracle happens though, Wrangle said there’s no better feeling than to deliver good news based on a therapy he and Rubinstein have developed.“It must be a pinnacle of human experience. It just feels fabulous.”