A quick run through the highlights and the headlines from the world’s biggest cancer meeting.
CHICAGO — The advertised theme for ASCO 2019 was “Caring for Every Patient, Learning from Every Patient,” but the leitmotif was — as it has often been in recent years — targeted therapy.
But there were a few twists in the ongoing targeted therapy epic this year: first the emphasis on biomarker guided targeted therapy and then — drum roll here — the “first ever overall survival benefit for a targeted therapy.”
The MONALEESA-7 investigators claimed bragging rights for the “first ever overall survival benefit” claim when they reported that adding the CDK4/6 inhibitor ribociclib to endocrine therapy significantly extended overall survival in younger women with advanced HR+/HER- breast cancer “with a 29% lower risk of death (hazard ratio for death, 0.71; 95% CI, 0.54 to 0.95; P = 0.00973 by log-rank test).” The study was also unique in that it was the first trial to test the benefit of a CDK4/6 inhibitor in a cohort comprised exclusively of premenopausal women.
All of the FDA-approved CDK4/6 inhibitors —palbociclib (Ibrance), abemaciclib (Verzenio), and ribociclib (Kisqali) — have demonstrated progression-free survival benefits, but an earlier study of palbociclib did not find an overall survival benefit, noted Sara Hurvitz, MD, of the UCLA Jonsson Comprehensive Cancer Center, who reported the MONALEESA-7 results at ASCO. The trial results were also published online by The New England Journal of Medicine.
But ASCO breast cancer spokesperson Harold J. Burstein, MD, PhD, of the Dana-Farber Cancer Institute in Boston, told BreakingMED that the survival benefit seen in MONALEESA-7 was likely to extend to all currently approved CDK4/6 inhibitors. And he was not alone in that judgment, as Angelo Di Leo, MD, PhD, declared that, based on MONALEESA-7 findings and some early results from a palbociclib study, CDK4/6 inhibitors should be “the new standard of practice” for the first-line treatment of premenopausal women with advanced HR+/HER2- breast cancer.
The overall survival for a targeted therapy — and the potential for a change in standard of care — was the headline on breast cancer at the meeting, but it was far from the only breast cancer news.
Other long anticipated results included:
- NALA III, which found neratinib plus capecitabine superior to lapatinib plus capecitabine as third-line therapy in HER2+ positive metastatic breast cancer.
- SOPHIA reporting that the investigational immune-enhancing monoclonal antibody margetuximab improved progression free survival in women with HER2+ metastatic breast cancer who were previously treated with at least two anti-HER2 regimens.
- FAKTION, a phase II study in postmenopausal women with estrogen receptor positive breast cancer, found that an AKT inhibitor added to fulvestrant demonstrated a significant benefit in progression-free survival versus fulvestrant plus placebo — more than doubling time to progression.
- IMpassion 130 drove home the value of testing all new triple negative breast cancer patients for PD-L1 and that Ventana SP142 is “the preferred assay.”
Recalling the second half of ASCO’s announced theme — “Learning from Every Patient” — metastatic cancer survivor, aka metavivor, Kelli Davis delivered powerful lessons as she addressed hundreds of oncologists gathered for an early morning session on ASCO’s final day, starting with this take home message: “Don’t call my disease chronic. That disrespects me and my disease, call it what it is: terminal. Don’t tell me that my metastatic breast cancer is now a chronic condition. Recognize that I’m living with a terminal disease.”
Stepping away from breast cancer, researchers reported a surprising finding in pancreatic cancer: a sustained response for two years and counting in a small subset of pancreatic cancer patients who carried germline BRCA 1 or BRCA 2 mutations when treated with olaparib, a PARP inhibitor, in the POLO trial, which was also published in The New England Journal of Medicine. Hedy L. Kindler, MD, of the University of Chicago, who reported the findings, said only about 4-7% of persons with metastatic pancreatic cancer will have the mutations, but finding out only requires a blood test. In the study, progression-free survival was doubled —7.4 months versus 3.8 months — and median duration of response was 24.9 months versus 3.7 months. But a few caveats emerged from the breathless reception of positive findings from a trial in metastatic pancreatic cancer: “interim overall survival data (at 46% maturity) showed no difference between arms. Final OS results will be evaluated at 69% data maturity,” Kindler said, adding that she thought that threshold might be reached by year’s end.
In what was a significant change of pace for a clinical science meeting traditionally devoted to late-breaking findings from mega-trials, ASCO spotlighted a series of studies investigating the clinical consequences of access issues, including one that claimed to provide evidence that the Affordable Care Act improves cancer care and another stating that surviving multiple myeloma may depend upon what insurer pays the bills and where the patient lives.
The words “practice-changing” are often loosely applied to results reported at medical meetings, but there was little push-back when researchers made that claim about results of a study in patients with advanced gastric cancer. What was surprising is the fact that the study found only modest benefit: the overall survival rate was 47% in pembrolizumab-treated patients versus 46% in patients randomized to platinum-based chemotherapy. The key difference, as Richard Schilsky, MD, chief medical officer of the American Society of Clinical Oncology, put it was in the quality of that survival. “Platinum-based chemotherapy is a tough therapy for gastric cancer patients, many of who are frail and undernourished,” said Schilsky, a GI cancer specialist. “If I had an alternative such as pembrolizumab that is not any worse than chemotherapy and has a much more favorable side effect profile, I would switch in a minute.”
Finally, there was more than just a “hat tip” to prostate cancer investigators during the big show in Chicago. Among the major studies unveiled here were TITAN and ENZAMET, both of which demonstrated significant benefit for men with metastatic hormone-sensitive disease. Both trials investigated treatment options in addition to testosterone suppression. ENZAMET recruited 1,125 men and randomized them to enzalutamide (n=596) or bicalutamide, nilutamide, or flutamide with or without docetaxel. The ENZAMET investigators found that, with or without docetaxel on-board, 83% of men treated with enzalutamide were alive at 3 years versus 70% of controls. TITAN studied the benefit of apalutamide and found, “the overall survival percentage at 24 months was 82.4% in the apalutamide group and 73.5% in the placebo group (hazard ratio for death, 0.67; 95% CI, 0.51-0.89; P = 0.005).”
By Peggy Peck, Editor-in-Chief, BreakingMED, a service of @Point of Care, LLC, which provides daily medical news reports curated to serve the unique needs of busy physicians and other healthcare professionals.