ESMO 2019: PARP and Prostate, SeaGen’s Win, KRAS Update & More

Xconomy National — 

The European Society for Medical Oncology meeting has wrapped up in Barcelona, the last major clinical cancer conference until December’s annual ASH meeting for blood diseases. We’ve highlighted a few top stories for you.

Amid all the fuss over cell, gene, and immunotherapies these days, an old-fashioned small-molecule class of drug called PARP inhibitors have steadily made progress in tough-to-treat cancers. We’ll bring you the latest results from PARP trials, as well as news about breast cancer, the suddenly hot target known as KRAS, a boost for the Northwest’s biggest biopharma company, and more.

PARP Progress

Several PARP inhibitors, known so because of the tumor-protecting enzyme they target, have been approved since 2014, first to treat some ovarian cancers and more recently breast cancer. Could prostate cancer be next?

AstraZeneca (NYSE: AZN) and partner Merck (NYSE: MRK) are furthest along, and on Monday disclosed results from their Phase 3 PROfound trial, which is testing their PARP inhibitor olaparib (Lynparza) against approved prostate cancer drugs abiraterone (Zytiga) or enzalutamide (Xtandi) in a genetic subset of patients who had already progressed on a hormone therapy.

Patients taking Lynparza had a median of 7.4 months of progression-free survival—that is, their tumors didn’t spread—compared to 3.6 months for those on Xtandi or Zytiga. They were 66 percent less likely to die or see their disease get worse.

There were Phase 2 results to highlight at ESMO, as well. In TRITON2, 23 of 57 (44 percent) prostate cancer patients with BRCA mutations responded to the Clovis Oncology (NASDAQ: CLVS) PARP blocker rucaparib (Rucabra). In a similar trial called GALAHAD, 12 of 29 patients (41 percent) responded to niraparib (Zejula), from GlaxoSmithKline (NYSE: GSK), though the British pharma enrolled sicker patients than Clovis did. Thus far, Rucabra and Zejula are “very comparable,” wrote RBC Capital Markets analyst Kennen MacKay in a research note. Lynparza, meanwhile, could be the “preferred treatment” of the PARP group, at least thus far, given it beat hormone therapy head to head, wrote SVB Leerink analyst Andrew Berens.

In ovarian cancer, PARP inhibitors are predominantly used to treat the subset of patients whose tumors have BRCA mutations. But big trials under discussion at ESMO, run by AstraZeneca and GSK, gave hints that the drugs could be used more widely patients whose tumors have different genetic signatures. GSK and AstraZeneca both want to expand the labels for their PARP blockers, as Reuters reports here.

KRAS Questions

The past year, a drug called AMG 510 from Amgen (NASDAQ: AMGN) has become one of the more closely watched experimental cancer medicines. It’s the first drug to inhibit the cancer protein KRAS—a known genetic driver of several cancers—and have an effect in patients. The Amgen drug targets the specific mutation KRAS-G12C, which is implicated in a fraction of extremely tough-to-treat cancers.

Amgen has been steadily adding data this year, with both promise and problems. That was the case at ESMO as well. In colorectal cancer, Amgen reported on 12 patients who have failed a median of four therapies and as many as 10. One responded to treatment—meaning the patient’s tumor partially shrank—and in 10 others, the tumors were kept in check. They remain on AMG-510.

Investors “may have been hoping for a higher response rate,” wrote SVB Leerink analyst Geoffrey Porges. But Porges believes AMG-510 is “viable” for colorectal cancer because patients who have tumor shrinkage might benefit for a longer time than typically expected.

Of note, there were no serious side effects, which leaves the door open to combine AMG-510 with other drugs, which Amgen is planning. Amgen shares remained flat. Shares of Mirati Therapeutics (NASDAQ: MRTX), which has a rival KRAS-G12C inhibitor in human testing, fell six percent.

Breast Cancer Steps

Xconomy has previously detailed immunotherapy’s obstacles in breast cancer. But it’s starting to make headway, particularly in triple-negative breast cancer (TNBC), an aggressive form that accounts for about 15 to 20 percent of cases. The FDA earlier this year approved the first immunotherapy for breast cancer—the Roche drug atezolizumab (Tecentriq) and chemotherapy, for a subset of TNBC patients. Another regimen highlighted at ESMO could soon follow.

Merck unveiled details of its 1,174-patient Keynote-522 study, which treated TNBC patients before surgery to remove their tumor, what’s known as “neoadjuvant” treatment. Head to head, Keytruda and chemotherapy beat chemo alone: 64.8 percent of Keytruda-chemo patients had no trace of cancer in the breast or lymph nodes on an imaging test, versus 51.2 percent of those who … Next Page »

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