Persistence Pays Off for Patient with Lung Cancer 

In December 2023, a space opened in a clinical trial at Dana-Farber of a novel targeted drug. Rosemary Conway, 68, who had stage IV lung cancer, was eager to fill it. She had been waiting nearly six years for a trial of a medicine that would target a specific genetic mutation driving the growth of her cancer – a mutation in the RAS family called KRASG12D.  

For decades, the RAS family of proteins was thought to be “undruggable,” meaning no medicine could block RAS. By 2018, however, that idea had been disproven. That same year, a RAS inhibitor was tested in a clinical trial for the first time, but it was for a different type of KRAS mutation than Conway’s.  

Conway’s thoracic oncologist at that time, Alice Shaw, MD, PhD, assured her that more RAS inhibitors would be coming.  

“We’ve had extraordinary advances in lung cancer treatment in the last two decades,” says Shaw. “We’ve seen the real impact these advances have had for many patients, and that progress is reason to have hope and to stay strong.” 

Conway, who lives in Wayland, Massachusetts, put her trust in Shaw. “My attitude has always been that there is going to be another trial and another treatment.” 

An Unexpected Diagnosis 

Lung cancer was the furthest thing from Conway’s mind when she was diagnosed in August 2017. At age 60, she was a runner and a regular at the gym. She had never smoked and held a high-energy job as a speech-language pathologist for young children.  

One day, she noticed a slight raspiness to her voice and saw a speck of blood in her palm after coughing. Her doctor prescribed antibiotics, thinking she had a respiratory infection.  

By September, she had the lower lobe of her left lung removed, along with a mass about the size of a plum. In October, she underwent surgery to remove her upper right lobe and with it, an apple-sized mass.  

Human lungs have five lobes – two in the left lung and three in the right.  Losing most of two lobes is significant, but Conway recovered well because she was physically fit. After surgery, she returned to the gym and resumed work until retiring at 65. 

After surgery, Conway received chemotherapy, but about seven months later, the cancer returned. Around that time, she also learned she had the KRASG12D mutation. RAS mutations switch proteins in the RAS family to an “always on” state, causing a constant flow of growth signals into the cell. This unchecked growth leads to cancer. 

RAS is the most commonly mutated oncogene – a gene that has the potential to cause cancer – in humans, with RAS mutations found in 20% of all cancers. These cancers are difficult to treat and are less likely to respond to chemotherapy. 

Strength Through Understanding 

Conway was determined to find an oncologist experienced in complex cases and rare mutations. She was drawn to Shaw’s credentials and her unique blend of clarity and warmth.  

“It is obvious that Dr. Shaw thought everything through before meeting with me, and that was a huge comfort,” says Conway. 

Shaw prioritizes complete transparency in patient care. “Patients benefit from understanding as much as possible about their cancer and talking through the different options,” says Shaw, chief of Strategic Partnerships at Dana-Farber. 

After undergoing surgery and chemotherapy, Conway participated in three clinical trials, selected through consultations with Shaw, David Barbie, MD, director of the Lowe Center for Thoracic Oncology, and experts from multiple cancer institutes.  

“Rosemary took the initiative to seek multiple opinions and is incredibly dedicated as an advocate for herself,” says Barbie, who is Conway’s current oncologist. “As oncologists doing clinical research, we want to collaborate widely across institutions, so patients participate in the best possible trial for them.”  

Two of the trials were ineffective against Conway’s cancer. She then underwent several courses of radiation and proton therapy. During the third trial, her lung capacity decreased dramatically. prompting her to leave the trial in the summer of 2023. 

“Rosemary had to really persevere and take a lot of risks with these trials while waiting for novel RAS inhibitors to become available,” says Shaw, who co-leads the Dana-Farber Center for RAS Therapeutics.  

Hope Realized 

In 2023, Barbie identified a trial of daraxonracib (formerly called RMC-6236), a pan-RAS inhibitor designed to block multiple RAS mutations, including KRASG12D. It was an ideal fit for Conway.  

Seven months later, she enrolled in the trial and began taking the drug, a nightly pill. The trial’s primary goal is to determine a safe and effective dose. Conway joined as the trial expanded to further evaluate one of the doses.  

Conway has been taking the drug for 14 months and her cancer has stopped growing. She’s also back in the gym, walking and lifting weights again.  

“I’m doing really well,” shares Conway, who is devoting increasing amounts of her time working as an advocate for other patients with lung cancer. “The trial is going smoothly, I feel fine, and I’m looking forward to continuing like this for as long as possible.”