Feature: Consequential takeaways from ASCO
As many of our readers are no doubt aware, the 2024 ASCO Annual Meeting took place in Chicago from May 30 through June 3. These summaries are some of the most notable news to come out of this year’s conference.
AstraZeneca’s Tagrisso (osimertinib) reduced the risk of disease progression or death by an impressive 84% compared with placebo in patients with unresectable Stage III EGFR-mutated (EGFRm) non-small cell lung cancer (NSCLC) after chemoradiotherapy. In the Phase III LAURA trial, median progression-free survival (PFS) was 39.1 months among those who received Tagrisso versus 5.6 months for the control group. Tagrisso also demonstrated a tumor progression benefit, with just 6% of patients in the Tagrisso group developing brain metastases within two years after treatment versus 28% of patients in the placebo group who did so.
The ASCO audience gave the results a standing ovation when presented during a Sunday plenary session. The trial’s principal investigator, Dr. Suresh Ramalingam, executive director of Winship Cancer Institute at Emory University, said the PFS results represent “a major breakthrough” for this patient population, for whom no targeted treatments are available, adding that Tagrisso “should become the new standard of care in this setting, based on these data.” Dr. David Spigel, chief scientific officer at the Sarah Cannon Research Institute in Nashville, Tenn., said during a press conference, “This will be practice changing.”
AstraZeneca and Daiichi Sankyo’s Enhertu (trastuzumab deruxtecan) slowed the progression of breast cancer by 5.1 months compared with chemotherapy in patients with hormone receptor-positive HER2-low metastatic breast cancer (following endocrine therapy) in the Phase III DESTINY-Breast06 trial. Median PFS was 13.2 months for patients who received Enhertu and 8.1 months for those treated with chemotherapy, representing what Dr. Lynn Schuchter, ASCO’s president, called an “unprecedented” 38% reduction in the risk of disease progression or death.
Of particular note, Enhertu reduced the risk of disease progression or death by 22% relative to chemotherapy in a subgroup of patients with HER2-ultralow expression — those with very low levels of the mutant protein Enhertu targets. Although this finding was not statistically significant, it suggests Enhertu could potentially be used in an earlier treatment setting for a larger population of patients.
Susan Galbraith, executive vice president of oncology research and development at AstraZeneca, told Reuters if Enhertu is approved for HER2 low and ultralow breast cancer after endocrine therapy, eight out of 10 women with metastatic breast cancer could be treated with the drug.
Novartis’ Scemblix (asciminib), a tyrosine kinase inhibitor (TKI), outperformed current standard-of-care TKI therapies — including Novartis’ Gleevec (imatinib mesylate) and second-generation TKIs — in patients with newly diagnosed Philadelphia chromosome-positive chronic myeloid leukemia (CML) in the Phase III ASC4FIRST trial. Results showed that 68% of patients treated with Scemblix achieved a major molecular response (MMR) after 48 weeks, compared with 49% of patients who achieved an MMR after receiving one of the comparator treatments. A deep molecular response, commonly considered a sign of remission in CML, was observed in 39% of patients in the Scemblix arm and 21% of those in the comparator groups.
Scemblix also demonstrated a superior safety profile compared with Gleevec and the second-generation TKIs. Greater tolerability could prove especially advantageous, as most patients with CML must continue treatment with a TKI for years. Analysts at Jefferies told investors the results “should position [Scemblix] as the new standard of care,” BioSpace reported.
Long-term follow-up results from the Phase III CROWN trial showed that 60% of patients treated with Pfizer’s Lorbrena (lorlatinib) for a specific type of lung cancer had no disease progression after five years, compared with just 8% of patients treated with Pfizer’s Xalkori (crizotinib). The trial evaluated the two drugs in previously untreated patients with anapestic lymphoma kinase (ALK)-positive advanced NSCLC. According to Pfizer, Lorbrena demonstrated an “unprecedented” 81% reduction in the rate of disease progression or death compared with Xalkori. The updated analysis also found that Lorbrena showed a 94% reduction in the risk of developing intracranial progression.
Benjamin Solomon, a medical oncologist at the Peter MacCallum Cancer Center in Melbourne, Australia, and the trial’s principal investigator, said the improvements in outcomes for patients with ALK-positive NSCLC “represent a remarkable advancement in lung cancer.” Some experts noted that a newer drug, Genentech’s Alecensa (alectinib), has replaced Xalkori as the standard of care for this patient population and, therefore, Xalkori is an inferior comparator. Lorbrena has not been evaluated in head-to-head trials with other next-generation TKIs.
Also worth noting, while Gilead Sciences provided detailed results from the Phase III EVOKE-01 study of Trodelvy (sacituzumab govitecan) showing that the drug only modestly improved overall survival in previously treated patients with metastatic or advanced NSCLC when compared with chemotherapy (median OS, 11.1 months for Trodelvy vs. 9.8 months for docetaxel), the study’s preliminary results had already been released in January.
More significant news about Trodelvy began circulating just ahead of ASCO: Based on top-line results from the Phase III TROPiCS-04 study, the drug failed to improve overall survival in previously treated patients with metastatic urothelial (bladder) cancer. There was also a higher number of deaths due to adverse events in the Trodelvy group as compared with the control arms. Because Trodelvy was granted an accelerated approval and TROPiCS-04 was intended as a confirmatory trial, it is unknown how these results will affect the drug’s approval for the bladder cancer indication. Gilead said it is continuing to analyze the data and will discuss next steps with the FDA.
And, while Miami-based Summit Therapeutics presented data from the Phase III HARMONi-A trial conducted by Akeso, Summit’s partner on a potential first-in-class bispecific antibody called ivonescimab, the buzz at the conference was all about a different Phase III trial: HARMONi-2. Investigators in HARMONi-A evaluated ivonescimab plus chemotherapy versus placebo plus chemotherapy in patients with EGFRm NSCLS. In HARMONi-2, however, investigators conducted a head-to-head comparison of ivonescimab and Merck’s Keytruda (pembrolizumab) as monotherapy in patients with NSCLC whose tumors have positive PD-L1 expression — and ivonescimab appears to have outperformed Keytruda in terms of progression-free survival.
An interim analysis of HARMONI-2 data revealed that ivonescimab demonstrated “a statistically significant and clinically meaningful improvement in PFS … compared to pembrolizumab,” Akeso stated in a press release. Pointing out that the HARMONi-2 study was conducted solely in China, analysts at Jefferies said this may have influenced the outcomes, as anti-VEGF therapies like ivonescimab have performed better in Asian populations than in non-Asian populations in previous clinical studies. Summit said detailed results from HARMONi-2 would be shared at a future medical meeting.
What else you need to know
Washington Health System is officially part of UPMC, one of the largest health care networks in Pennsylvania. The organizations made their affiliation official on June 1, with WHS being renamed UPMC Washington and UPMC Greene (after the counties in which WHS’ two hospitals are located). While financial terms of the affiliation were not disclosed, UPMC committed to invest at least $300 million in the next decade to enhance clinical services and upgrade facilities at UPMC Washington and UPMC Greene, according to the announcement. Brook Ward, who served as president and CEO of WHS, is now president of UPMC Washington and UPMC Greene. The two former WHS hospitals will maintain a local board of directors comprising 11 legacy WHS board members and five new UPMC members.
Oregon Health & Science University and Legacy Health took the next step toward uniting as a 12-hospital system under the OHSU Health name, signing a a binding, definitive agreement. The combined system will be one of the largest providers of services to Medicaid members in Oregon and will serve patients from across the Pacific Northwest. The combined health system would have more than 100 locations and an estimated 30,000 employees. OHSU, a partially state-funded public corporation, agreed to a capital commitment of approximately $1 billion over 10 years, which would be financed primarily through bond offerings. The organizations said they would submit an application to Oregon’s Healthcare Marketplace Oversight Program in the coming months, after which the regulatory review process will begin.
Cigna’s Evernorth Care Services intends to lay off 261 employees in Arizona, according to a WARN notice, and will close multiple locations as it consolidates care sites. The company’s strategy is to cut certain specialty services and focus on integrated primary care in an effort to adapt to market conditions, Becker’s Payer Issues reported. The Evernorth Care Group website shows 20 health care centers in the Greater Phoenix area; four offer urgent care. In January, Evernorth Care Group sold its outpatient imaging centers in Phoenix to Arizona Diagnostic Radiology Group, a joint venture formed in 2020 between Los Angeles-based RadNet and Dignity Health/CommonSpirit Health.
Illumina’s board of directors approved the spin-off of Grail, which is anticipated to occur on June 24. Illumina has applied for Grail’s listing on the Nasdaq under the symbol GRAL. Illumina’s shareholders will retain their shares of Illumina common stock and receive one share of Grail common stock for every six shares of Illumina stock they hold on June 13, the record date of the distribution. The board declared a pro rata dividend of 85.5% of the outstanding common stock of Grail to Illumina’s shareholders, and Illumina will retain the remaining 14.5%, according to the press release.
Geron received FDA approval for its Rytelo (imetelstat), a first-in-class telomerase inhibitor, for the treatment of adults with low- to intermediate-risk myelodysplastic syndromes (MDS) with transfusion-dependent anemia when erythropoiesis-stimulating agents (ESAs) are not (or no longer) an option. The Foster City, Calif.-based biopharma company began developing the drug 33 years ago.
What we’re reading
Unanswered Questions And Unintended Consequences Of State Prescription Drug Affordability Boards. Health Affairs, 6.5.24
Scaling National E-health: Best Practices From Around the World. McKinsey & Company, 6.3.24
Medical Artificial Intelligence and Human Values. NEJM, 5.29.24
