Intercepting the Play

MOST NOVEL CANCER TREATMENTS aim to help patients fight advanced disease, but some approaches being developed by Stand Up To Cancer pursue a different goal: creating a defense against the illness before it gains that much ground.

Known as SU2C, the 10-year-old organization funds collaborative work by 24 scientific “dream teams” and raises awareness through celebrity ambassadors. SU2C calls certain trials “cancer interception” efforts because they’re designed to arrest the disease in its early stages, so it doesn’t progress or spread. The hope is that the findings will turn patients into long-term survivors. Many of the studies focus on cancer immunotherapy.

“Stand Up To Cancer has put a stake in the ground when it comes to pursuing the whole notion of cancer interception,” Sung Poblete, Ph.D., RN, the organization’s president and CEO, told CURE®. “We had a summit on this chaired by Nobel prize winner Elizabeth Blackburn, Ph.D., in November 2016, because we wanted to see if we could move the field toward treating cancers at earlier stages, when it could be easier. We’ve launched four separate cancer interception teams: two in lung cancer and two in pancreatic cancer.”

Meanwhile, additional SU2C dream teams are also advancing cancer interception, with promising findings emerging from one of those studies.

The trial tested immunotherapy before surgery in patients with operable stage 1 to 3 non-small cell lung cancer (NSCLC), and the results were reported in April during the annual meeting of the American Association for Cancer Research in Chicago. Researchers embarked on the trial to seek an alternative to platinum-based chemotherapy before surgery, which they said improves survival by just 5 percent compared with surgery alone. Moreover, they wrote in their paper about the study, the rate of serious or severe side effects associated with chemotherapy is above 60 percent.

Study participants were given Opdivo (nivolumab), which quiets the activity of the protein PD-1 so it can no longer keep the immune system in check; this frees up the body’s disease-fighting T cells to recognize and attack cancer. An initial dose of Opdivo was given to 21 patients, who took a second dose two weeks later; after another two weeks, they underwent surgery. After their tumors were removed, some of the patients took maintenance chemotherapy or radiotherapy to help prevent recurrences.

Surgeons were able to entirely remove tumors from all but one patient, and of those 20 patients, nine (45 percent) had a major pathological response — very little cancer remained in their bodies. For the sake of comparison, the authors cited a separate study of presurgical chemotherapy in patients with nonsquamous NSCLC, in which 22 percent of patients experienced a major pathological response.

The dream team found that patients whose tumors had more genetic mutations were the most likely to respond to Opdivo, although a tumor’s expression of the protein PD-L1 — often associated with immunotherapy’s effectiveness — did not influence results.

Twelve months after treatment, 80 percent of the 20 patients who had undergone complete surgical resections were alive and recurrence-free, the authors reported. At 18 months, recurrence-free survival in that group was 73 percent.

“We found that (nearly half of the) patients who received the immunotherapy before surgery did so well that there was little evidence of cancer remaining upon follow-up,” Poblete said. “The patients’ immune systems likely destroyed any circulating tumor cells, which otherwise could have taken hold and led to recurrence and metastases.” The study’s researchers determined that the surgery itself distributed the dangerous cells into the bloodstream — and “giving a PD-1 inhibitor before surgery created an autovaccine to help destroy them,” she said.

Treatment-related side effects occurred in five of 22 patients who took presurgical Opdivo (including one who was later deemed ineligible for the study), and all but one of those reactions were mild or moderate, the authors reported.

Due to those promising results, Poblete said, a phase 2 trial in patients with similar disease (NCT02259621), which is enrolling in New York City and Washington, D.C., will test presurgical Opdivo alone or paired with the immunotherapy Yervoy (ipilimumab). In addition, a global phase 3 presurgical trial is testing the immunotherapy pair compared with two other regimens: chemotherapy by itself or administered with Opdivo (NCT02998528).

SU2C served as a catalyst to get the concept of presurgical immunotherapy off the ground, according to Poblete. “When we started working in this area in 2013, presurgical administration of immunotherapy was something different and not yet tested,” she said. “Now, 70 other neoadjuvant trials have been launched by different pharmaceutical companies across many kinds of solid tumors.”

For Poblete, an interview with a participant in SU2C’s lung cancer interception trial underscored the importance of early intervention.

“He explained that he had recovered really quickly from the treatment and was back on the golf course four weeks after surgery swinging away, and feels better now than he did before the treatment,” she recalled. “It’s important for us to think about a patient’s quality of life, and it gave me a little bit of hope.”

Another early intervention trial overseen by SU2C is being conducted at the University of Texas MD Anderson Cancer Center in Houston. The Making Genetic Testing Accessible (MAGENTA) trial invites woman at high risk of inherited ovarian cancer to undergo free genetic testing for 19 mutations so that those who have the glitches can take disease-prevention measures. Patients don’t have to travel to MD Anderson to participate — they communicate online, mail their saliva for testing and receive genetic counseling either online or by phone. “Our hope is that making genetic testing accessible, without requiring (women) to travel to their health care providers, will save more lives,” leaders state on the study’s web page at magenta.mdanderson.org.

Yet another interception project on the near horizon, the PROMISE study, will focus on identifying and treating high-risk cases of smoldering myeloma or monoclonal gammopathy of undetermined significance.

Its aim: Prevent these precursor conditions from developing into the full-blown malignancy multiple myeloma. The study will start enrolling Sept. 1. Study leaders from SU2C’s Multiple Myeloma Dream Team plan to test 50,000 people identified via social media and other outreach approaches and find about 3,000 with the asymptomatic precursor conditions. The researchers will follow the progress of these patients and use their samples to discover biomarkers that predict progression to multiple myeloma. The team will also work to develop treatments for high-risk myeloma and its precursors.

SU2C couldn’t pave the way for new discoveries without the involvement of patients, and the organization is committed to helping those who are eligible and interested to find appropriate clinical trials — either its own or those run by others. A free, easily searchable database of trials can be found on its website at StandUpToCancer.org/clinicaltrials. The site also helps acquaint visitors with the clinical trial experience.

“There’s easy-to-understand information for patients and caregivers,” Poblete said, “including videos that explain the myths associated with clinical trials, as well as complex medical ideas: epigenetics, immunotherapy, informed consent, immunization and looping in your own medical team to see if a trial is right for you.”