November 4, 2015
By Bob Tedeschi Matthew Orr/STAT
Linnea Olson, an artist and shop owner in Lowell, Mass., knew the experimental drug she was given might save her life. She also knew it might kill her.
Olson, who had been diagnosed with a form of lung cancer, had exhausted conventional chemotherapy options several years ago when her oncologist told her about the drug — one that might successfully treat a mutation in her tumor. As one of the first patients to receive the drug, Olson said she had no way of knowing whether it would be toxic.
“But when you’re chased by a bear to the edge of a cliff, you jump,” Olson said.
Olson jumped — not once, but three times over the following years, each time trying a new targeted therapy that worked for a short period, until she became resistant to the drug. Today, Olson’s health remains stable, but she’s nervous: There’s no obvious next treatment.
The growing ability of medical science to pull patients back from the brink of death is a credit to targeted therapies, in which doctors search a person’s tumor for a genetic mutation that controls the disease, and deliver a drug to counteract the mutation.
In many cases, the results have been nothing short of extraordinary. Some breast cancer patients treated with a drug called Herceptin, for instance, have been living cancer-free for more than a decade. But more typically, the effects of the drugs wear off after six or nine months.
Linnea Olson in her studio in Lowell, Mass.
Matthew Orr/STAT
Linnea Olson in her home in Lowell, Mass.
For patients like Olson and others, the therapies have led to emotional exhaustion from facing death over and over again: repeatedly saying goodbye to loved ones, making preparations for the end of their lives, and dealing with uncertainty.
“There is just a resounding emotional thud when you are forced to acknowledge that the world will go on, but that it will do so without you,” Olson said.
“The feelings that I am least proud of were that some other woman would step into the void where my life had been. It was so, so hard.”
Dr. Vicki Jackson, an internist and chief of palliative care at Massachusetts General Hospital in Boston, said the impact is heightened because targeted therapies work so well for some patients.
“It’s amazing, because people can live like they don’t have cancer, just by taking a pill,” she said. “But patients either expect it’ll happen forever, or the roller coaster ride of waiting to see whether there’s another trial drug … gets incredibly stressful.”
In some ways, such issues are not new to cancer treatment.
Patients with certain forms of lymphoma, for instance, can experience prolonged remissions repeatedly. And those who experience disease recurrences frequently respond to second-line and third-line chemotherapy regimens for limited periods before growing resistant to the drugs.
Still, Jackson said, most patients who undergo chemotherapy after a recurrence follow a more steadily downward trajectory.
“With targeted therapies, it’s like the disease melts away and patients feel almost like themselves,” she said. “They’re not getting signals from their body that time is shorter.”
When the disease does return, patients’ conditions can deteriorate precipitously, leaving them again to confront the emotional, physical, and logistical issues that come at life’s end.
Phyllis Merchant, of Ashland, Mass., said her sister, who had lung cancer, had undergone four targeted therapies when one stopped working last December. Her liver had failed and the medical team told her she had only a few days to live.
Merchant’s sister called close friends and family to her hospital room, including her husband of 35 years, two adult children, and two grandchildren who’d been living in the family’s home for years.
“It was incredibly hard, but she found the emotional and physical strength to share final moments with the people closest to her,” Merchant said.
Then, a late round of genetic testing revealed that she had a mutation that might be susceptible to another targeted treatment.
“She was overwhelmed by the thought of re-engaging with daily life, knowing she would later need to say her goodbyes and make peace with dying all over again,” Merchant said. “Because her health declined so quickly, as a family we weren’t prepared yet for her to go. She understood this, and also wanted to spare us from her dying near Christmas.”
She went forward with the treatment and quickly responded — so well, in fact, that she was able to spend Christmas with her family, return to work, and enjoy more than five months of relatively good health. When she relapsed and grew very ill again earlier this summer, her oncologist approached her about seeking yet another treatment, and she declined. She died in July.
Left: Phyllis Merchant in her home in Ashland, Mass. Right: Phyllis Merchant, far right, in a family portrait with sisters Maureen Kynoch, far left, and Patti Bowen, and parents Donald and Muriel Merchant. The family photograph was taken in the summer of 2011, after Patti and her father were diagnosed with cancer.
Alissa Ambrose/STAT, Courtesy Phyllis Merchant
Left: Phyllis Merchant in her home in Ashland, Mass. Right: Phyllis Merchant, far right, in a family portrait with sisters Maureen Kynoch, far left, and Patti Bowen, and parents Donald and Muriel Merchant. The family photograph was taken in the summer of 2011, after Patti and her father were diagnosed with cancer.
“We all accepted her decision, knowing it’d be too hard for her to come back from the brink again,” Merchant said. “At the same time, having experienced one ‘near-miracle’ recovery, I found it difficult to give up hope for another.”
Dr. Cardinale Smith, an oncologist and palliative care specialist at Mount Sinai Hospital in New York, said such issues have become common.
“I haven’t had a patient decline treatment yet, but I’ve seen folks struggling with it. The struggle is real, and I don’t have a good answer for it,” she said. “The science is taking off, and we’re scrambling to figure out how to deal with it.”
Smith said patients grow fatigued from the treatment themselves, “but it’s also depression and anxiety around the uncertainty of their prognosis. It’s like, ‘I’m feeling better again, but how long will it last? And how do you plan your life around that? Do I keep working? Do I spend it all in Las Vegas?’”
Only about 20 percent of cancer patients can benefit from targeted therapies, said Dr. Thomas J. Lynch Jr., the chief executive of the Massachusetts General Physicians Organization and formerly the physician-in-chief of Smilow Cancer Hospital at Yale-New Haven.
That number is expected to grow steadily, though. The Obama administration has pledged $215 million in federal funding in 2016 for so-called precision medicine, an approach that is based largely on targeted therapies and that stresses treatments based on individual patients’ genes and other characteristics.
Immunotherapy, which stimulates a patient’s immune system and can include targeted genetic components, is also becoming more common.
Meanwhile, the rise of targeted therapies has complicated discussions about how best to manage the end of one’s life when the endpoint can suddenly vanish.
“I see it with many patients,” said Dr. Alice Shaw, an oncologist at Mass. General. “These options are coming out so fast and the results are so dramatic, it’s made end-of-life care even more complicated than it already was.”
Olson, the Lowell artist, knows just how complicated it can get. Before she began her first targeted therapy in 2008, she was told she had only months to live.
She said the next few months were emotionally tumultuous, as she ruminated over never having the chance to see her younger son grow up or to see her grandchildren.
Olson said she tried to “soak in all the love and memories I could, not only with