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ASCO Abstracts: Breast Cancer, Precision Treatments in the Spotlight

Xconomy National — 

The world’s biggest annual cancer conference is just around the corner. Data presented at the American Society of Clinical Oncology meeting each year can change medical practice and make or break companies whose drugs are under the microscope. That’s what makes even the “abstracts,” or snippets of data revealed a few weeks before the meeting, so noteworthy.

This year’s ASCO abstracts were posted online Wednesday, setting off an annual information frenzy. To provide context to the chaos, Xconomy has rounded up noteworthy data in two areas: advances in breast cancer treatment and drugs that target genetic subsets of various cancers. Let’s get right to it.

Breast Cancer

—High-fat, low-carbohydrate diets are all the rage, although whom they help, and how, gets complicated fast.

Add another confounding layer to the picture. At ASCO, researchers will discuss results of a large randomized study that shows a low-fat diet might help reduce a woman’s risk of dying from breast cancer. The 50,000-patient, 20-year study, known as the Women’s Health Initiative Dietary Modification trial, found that post-menopausal women who ate a low-fat diet with fruits, vegetables, and grains were 15 percent less likely to get breast cancer and 21 percent less likely to die from the disease than those on a higher-fat diet.

One interesting detail: the treatment group was supposed to reduce fat intake to 20 percent of total calories per day. They didn’t quite hit that mark, yet they still benefited. “The balanced diet we designed is one of moderation, and after nearly 20 years of follow-up, the health benefits are still accruing,” said lead investigator Rowan Chlebowski, of the Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, on a press call.

Full details of the study will be presented at ASCO. Here’s more from Targeted Oncology.

—Breast cancer that expresses the protein HER2 is a particularly aggressive form of the disease, accounting for about 20 percent of cases. There are many HER2-targeting drugs, and the combination of such drugs with chemotherapy is the standard of care. But patients often develop resistance. Two drugs to treat these patients have Phase 3 results coming at ASCO.

In a study called SOPHIA, margetuximab is being studied in combination with chemotherapy, and compared with against trastuzumab (Herceptin) and chemotherapy in patients who have failed at least two HER2-targeting drugs. Its developer Macrogenics (NASDAQ: MGNX) reported that the combination appears to help patients live a median of 1.7 months longer than trastuzumab-chemotherapy so far, and 6.8 months longer in a particular genetic subgroup of patients. The results are “better than we expected,” wrote ISI Evercore analyst Umer Raffat. Macrogenics shares climbed 13.7 percent.

The Puma Biotechnology (NASDAQ: PBYI) drug neratinib (Nerlynx) is already approved with trastuzumab for HER2-positive patients after surgery. But a Phase 3 study, NALA, aims to expand its use. A combo of neratinib and chemotherapy held tumors in check for 47.8 percent of patients after 6 months and 28.8 percent after a year, compared to 37.8 percent and 14.8 percent, respectively, for the combination of lapatinib (Tykerb) and chemotherapy, which is often used as a second-line treatment. But it’s not clear if the neratinib-chemotherapy duo helped patients live longer. Experts “have suggested that an overwhelming benefit over Tykerb would be needed to justify using Nerlynx” in these patients, wrote SVB Leerink analyst Andrew Berens. “We do not believe these data clear that bar.” Puma shares ticked up 2.6 percent nonetheless.

Precision Steps

—It’s well known that mutations to the gene KRAS occur in about 25 percent of all cancers. But researchers have failed to develop a drug that can lock onto the slippery surface of the mutated KRAS protein. A new crop of drugs aims to change that. They target a range of different tumors that share a specific KRAS mutation known as G12C.

The first to reach human testing is AMG510, an antibody from Amgen (NASDAQ: AMGN). Amgen provided a glimpse of the first human test. The results: two of nine evaluable patients with G12C mutations who have failed multiple therapies responded to treatment. Those numbers aren’t jaw-dropping, but the data are only initial results from patients on the lowest dose of AMG510 being tested. RBC Capital Markets analyst Brian Abrahams anticipates that the full ASCO presentation, to include patients receiving higher doses, will show better responses.

The results will be closely watched, and Amgen isn’t alone. Mirati Therapeutics (NASDAQ: MRTX) has another KRAS G12C blocker, MRTX849, in human testing. And Moderna (NASDAQ: MRNA) and Merck (NYSE: MRK) have an experimental KRAS-targeting cancer vaccine that is also in its first tests. Stat has more here.

—Since 2017, the FDA has approved two drugs that target a tumor’s DNA fingerprint, no matter where in the body that cancer is found. First came pembrolizumab (Keytruda) for patients whose tumors have one of two genetic problems known as microsatellite instability-high or mismatch repair deficiency. Then came larotrectinib (Vitrakvi) for patients whose tumors have a gene, NTRK, abnormally fused to another gene. The drug’s success spurred Eli Lilly (NYSE: LLY) to buy larotrectinib’s owner Loxo Oncology for $8 billion.

The third could come in August, when the FDA will decide whether to approve entrectinib, which Roche grabbed when it bought Ignyta for $1.7 billion. Like larotrectinib, entrectinib is for people whose tumors have NTRK fusions. But it’s also under review to treat non-small cell lung cancer patients whose tumors have an alteration known as a ROS1 fusion.

Roche’s ASCO abstract said that in a study called STARTRK-NG, entrectinib shrank the tumors of all 11 children and adolescents whose tumors had NTRK, ROS1, or ALK fusion-positive solid tumors. There will be more data at the meeting. Roche will present combined results from three studies of entrectinib in patients whose cancer has spread to the brain; it will also compare entrectinib with the Pfizer drug crizotinib (Xalkori) in patients with ROS1-positive non-small cell lung cancer.

Here’s more on entrectinib, larotrectinib, and the road ahead for tissue-agnostic drugs.

Image of metastatic breast cancer by Ed Uthman via Creative Commons.