By Peggy Peck, Editor-in-Chief, BreakingMED

In advance of the American Society of Clinical Oncology meeting May 31-June 4, 2019, ASCO hosted a press briefing to highlight five of the more than 2,400 abstracts that will be presented in Chicago. The reports below describe those studies.

Can a Dietary Intervention Prevent Breast Cancer Deaths?
A Long Look Back at the Women’s Health Initiative Offers an Answer

Following a cohort of postmenopausal women for almost 20 years has turned up what is being reported as “proof” that a dietary intervention can prevent breast cancer deaths.

That was the take home message offered by Rowan T. Chlebowski, MD, PhD, of the Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center in Torrance, California, during a press briefing highlighting a sampling of studies accepted for the American Society of Clinical Oncology meeting.

Chlebowski hangs that claim on analysis of long-term follow-up of women enrolled in the Women’s Health Initiative (WHI), a National Institutes of Health study of 48,835 postmenopausal women. The WHI had a lot of moving parts, one of which randomized women to a low-fat dietary intervention while half the sample followed a normal diet. After more than 8 years, the women in the low-fat arm lost about 3% of body weight, but did not have a statistically significant lower risk of invasive breast cancer. But at that time the researchers added a hopeful note that they observed nonsignificant trends “suggesting reduced risk associated with a low-fat dietary pattern indicate that longer, planned, nonintervention follow-up may yield a more definitive comparison.”

Chlebowski and colleagues now detail the results from that “longer, planned, nonintervention follow-up,” and report: “Now, after long-term, cumulative 19.6 year (median) follow-up, with 3,374 incident breast cancers, the significant reduction in deaths after breast cancer continued (with 1,011 deaths, HR 0.85 95% CI 0.74-0.96) and a significant reduction in deaths from breast cancer (breast cancer followed by death attributed to the breast cancer) emerged (with 383 deaths, HR 0.79 95% CI 0.64- 0.97).” That’s a 15% reduction in all-cause mortality after a breast cancer diagnosis and a 21% lower risk of breast cancer mortality among women following what Chlebowski called a very “doable, balanced diet that cut fat intake to about 20-25% of calories and increased fruits, grains and vegetables.”

ASCO president Monica M. Bertagnolli put it this way: “There is no downside to this.”

ASCO Abstract 520: “Low-fat dietary pattern and long-term breast cancer incidence and mortality: The Women’s Health Initiative randomized clinical trial.”

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Pediatric Precision Medicine: First Find the Target
Studies Suggest Age Is No Barrier to Targeted Therapy

Pediatric cancers are killers that often elude approved therapies, but the advent of precision medicine is creating a renaissance in pediatric oncology, as illustrated by two studies selected for the ASCO preview program.

The first, a status report from the National Cancer Institute-Children’s Oncology Group Pediatric Molecular Analysis for Therapy Choice (NCI-COG Pediatric MATCH), which was launched in 2017, is the story of a good idea that appears to be working better than expected. The concept: tumor sequencing of tumor samples from children and young adults whose cancers do not respond to treatment could identify genetic targets that could then be matched to investigational, targeted therapies.

Will Parsons, MD, PhD, of Baylor College of Medicine in Houston said the expectation was that 10% of the tumor samples would yield matches. Thus far, the program has collected 400 tumor specimens, completed DNA sequencing on more than 350, and found eligible matches for 24% of those samples, and 10% of the patients who had tumors sequenced and matched are now receiving targeted therapy.

The second pediatric precision medicine report involved entrectinib — not one of the 10 targeted therapies in the NCI-MATCH. Giles W. Robinson, MD, a pediatric neuro-oncologist from St. Jude Children’s Research Hospital in Memphis discussed very early findings (I/IB) from a study that included 29 patients age 4.9 months to 20 years. The patients had a variety of central nervous system tumors, neuroblastomas, or other solid tumors, and responses were observed in 12 of 28 evaluable patients. “Our results show that children with life-threatening cancers can benefit greatly even after other conventional therapies have not worked – we’ve seen some rapid and durable responses, which is very gratifying,” Robinson said.

Entrectinib is given orally and targets TrkA/B/C, ROS1, and ALK tyrosine kinases. Robinson said the results “were striking and fast in all tumors that harbored NTRK1/2/3, ROS1 or ALK fusions.”

Abstract 10011: Identification of targetable molecular alterations in the NCI-COG Pediatric MATCH trial.

Abstract 10009: Phase 1/1B trial to assess the activity of entrectinib in children and adolescents with recurrent or refractory solid tumors including central nervous system (CNS) tumors.

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 Determining Dose: It’s All About the Patient
When the Patient Is Elderly and Frail, Consider Low Dose

Some cancers are more common in elderly — often frail— persons, and Peter S. Hall, PhD, a medical oncologist from the University of Edinburgh, suggests that those points should be factored into the mix when calculating the best chemotherapy course. Known efficacy is only one consideration, he said as he explained the hypothesis for the GO2, a phase III trial of 514 patients with advanced gastroesophageal cancer.

He noted that most cancer trials that provide the evidence used in developing recommended treatments don’t include the frail elderly, yet gastroesophageal cancer is usually diagnosed at a late stage and the average age at diagnosis is 68. In the trial, patients were randomized to one of three regimens:

  • Level A was 130 mg/m2 of oxaliplatin given once every 21 days and a 625 mg/m2 dose of capecitabine twice a day given continuously;
  • Level B was 80% of Level A dosage;
  • Level C was 60% of Level A dosage.

After 9 weeks, patients were assessed for overall treatment utility. Bottom line: the lowest tested dose was noninferior to the highest dose in terms of delaying disease progression and minimizing side effects. And patients in that lowest dose reported the best quality of life. ASCO president Monica C. Bertagnolli, MD, said Hall’s study was a good example of the “less is more” approach to oncology, which is becoming more common since it is “paying off for patients’ quality of life.”

Abstract 4006: Optimizing chemotherapy for frail and elderly patients (pts) with advanced gastroesophageal cancer (aGOAC): The GO2 phase III trial.

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Lenalidomide May Prevent Smoldering Multiple Myeloma from Progressing
But the Treatment Is Toxic

If a patient knew they had a high risk of developing multiple myeloma, it is likely that the patient would be willing to take a pill to eliminate that risk. That simple concept was the impetus for a trial of lenalidomide in smoldering multiple myeloma (SMM).

Sagar Lonial, MD, Chief Medical Officer at Winship Cancer Institute of Emory University, Atlanta, said patients who have been told they have smoldering multiple myeloma typically become anxious about the possibility of developing full-blown disease or take a wait-and-see attitude. “It’s gratifying to know that, especially for the first group of patients, there may now be a viable treatment option,” he said.

The E3A06 trial enrolled patients with intermediate or high-risk SMM in two phases. In phase II, 44 people received lenalidomide — which is an analogue of thalidomide — to assess potential efficacy. In phase III, investigators randomly assigned 182 people to a 25 mg pill of lenalidomide daily for 21 of the first 28 days of a therapy cycle, or observation, and stratified them based on whether they were diagnosed with high-risk SMM within that past year or more than a year after enrollment.

Lonial said that 3 years after enrollment in the phase II trial, 87% of participants were still healthy with no progression to multiple myeloma. But lenalidomide is not an easy drug to take: 80% of the people in phase II and 51% of those in phase III discontinued the medication. Still, Lonial said that balanced against the reality of multiple myeloma, a toxic therapy may appeal to many people. ASCO president Monica M. Bertagnolli, MD, cautioned, “This approach is not for everyone…because it comes with potentially heavy side effects and costs, so watching and waiting still has clear advantages that every patient should discuss with their doctor.”

Abstract 8001: E3A06: Randomized phase III trial of lenalidomide versus observation alone in patients with asymptomatic high-risk smoldering multiple myeloma.

 

The ASCO meeting, which kicks off May 31 in Chicago, will feature 2,400 abstracts, and another 3,200 submitted abstracts will be published online. Follow BreakingMED coverage at Physicians’ Weekly.