In the first episode of a special daily series during the 2024 ASCO Annual Meeting, Dr. John Sweetenham shares highlights from Day 1, including exciting data on the CROWN trial in NSCLC, the ASC4First study in chronic myeloid leukemia, and the effects of high-deductible health plans on cancer survivorship.
TRANSCRIPT
Dr. John Sweetenham: I'm Dr. John Sweetenham, the host of the ASCO Daily News Podcast. I'm delighted to bring you a special series of daily episodes from the 2024 ASCO Annual Meeting and to share my top takeaways on selected abstracts.
Today, I'll be reviewing exciting new data in chronic myeloid leukemia, remarkable outcomes for patients with ALK-positive non-small cell lung cancer, and a compelling study on the effects of high deductible health plans on cancer survivorship.
My disclosures are available in the transcript of this episode.
LBA6500, the ASC4FIRST trial, is a phase 3 combination of asciminib with the current standard of care tyrosine kinase inhibitors, those being imatinib, nilotinib, dasatinib and bosutinib for the first line treatment of patients with chronic myeloid leukemia. The data from this large multinational study, conducted in 29 countries, were presented by Dr. Timothy Hughes from the Royal Adelaide Hospital in Australia. Some patients with chronic phase CML respond well to tyrosine kinase inhibitor therapy, and about one-third may eventually be able to stop therapy and will remain in remission, the so-called treatment free remission or TFR. Unfortunately, almost half of patients eventually need to change therapy due to resistance and intolerance, and most patients will need to remain on therapy for many years, possibly for life.
Asciminib is the first BCR-ABL1 inhibitor to specifically target the ABL myristate pocket or STAMP and was designed to be highly potent but also highly specific, thus minimizing side effects and toxicity. In this large trial, which is the first randomized head-to-head comparison of asciminib with other tyrosine kinase inhibitors, 405 patients were randomized 1:1 to receive either asciminib at a dose of 80 milligrams daily or another investigator-selected TKI. The groups were well balanced for all patient characteristics, including ELTS risk. The primary objectives of the study were to compare the major molecular response rate at 48 weeks with an additional analysis for the patients who received imatinib as the investigator-selected TKI. With median follow-up at 16.3 months for patients receiving asciminib and 15.7 months for those receiving the other TKIs, the 48-week MMR rates were 68% for asciminib compared with 49% for the other investigators-selected TKIs.
The rates of MR4 after 48 weeks, a deep molecular response which is a prerequisite to be considered for treatment free remission, were 39% for asciminib compared to 21% for the investigator-selected TKI. Tolerability and safety were excellent for asciminib, with only 5% discontinued due to toxicity compared to 10% for the other TKI arm. Frequently observed toxicities with asciminib included thrombocytopenia and neutropenia. The investigators concluded that asciminib is the only agent to show a statistically significant improvement in efficacy and toxicity in this patient group when compared with all other TKIs, and that asciminib has the potential to become the preferred standard of care for the first line treatment of CML. Follow-up on the study continues, but there is no question that these are exciting and probably practice-changing results.
The next exciting study, LBA8503, was presented by Dr. Benjamin Solomon from the Peter MacCallum Cancer Centre in Melbourne, Australia. This presentation was an update of the CROWN study for patients with previously untreated advanced ALK-positive non-small cell lung cancer. Lorlatinib is a third-generation brain-penetrating ALK inhibitor which was compared with crizotinib in the CROWN-3 study. This phase 3 study enrolled 296 patients randomly assigned to lorlatinib 100 milligrams once daily or crizotinib 250 milligrams twice daily. The interim results showed a 72% reduction in the risk for progression or death with lorlatinib compared with crizotinib and formed the basis for the March 2021 FDA approval of the drug for metastatic ALK positive non-small cell lung cancer. A subsequent post hoc analysis at three years showed continued progression free survival benefit with lorlatinib compared with crizotinib.
Earlier today, Dr. Solomon presented a further post hoc analysis of the study at 60.2 months of median follow-up. Among the entire patient population, the median PFS was not reached with lorlatinib compared with 9.1 months with crizotinib. At 60 months, the PFS rate was 60% with lorlatinib compared with only 8% with crizotinib. The PSF benefits with lorlatinib were seen across all patient subgroups. The improved control of central nervous system metastatic disease, which was observed in the earlier reports, has been confirmed in this recent analysis. Among those patients with baseline brain metastases, the median PFS with lorlatinib was not yet reached compared with six months with crizotinib. More than half of patients with baseline brain metastases were progression free at 60 months.
But the benefit of lorlatinib is certainly not confined to patients with brain metastases. Lorlatinib also significantly improved progression-free survival among patients without metastases. At 60 months, 63% of patients without baseline brain metastases assigned to lorlatinib were progression free, compared with only 10% of those assigned crizotinib. These are remarkable results. As Dr. Solomon stated in his conclusion, 60% of patients on lorlatinib are still progression free and 92% are progression free in the brain. No new safety signals were seen and the improved efficacy over crizotinib was seen across all risk groups. These results are unprecedented in patients with ALK-positive non-small cell lung cancer.
Concerning data were presented today by Dr. Justin Barnes from Washington University. Dr. Barnes presented results from a retrospective study in Abstract 11005 which showed whether a patient with cancer has high-deductible health insurance can play a role in their survival. Although previous studies have shown care disparities for those with high-deductible plans, this report focuses specifically on effects on survival and concludes that cancer survivors with high-deductible health plans had a greater risk of mortality both overall and from cancer. High-deductible insurance was defined as costing between $1,200 and $1,350 annually for individual insurance, or between $2,400 and $2,700 annually for a family plan. Investigators used data from the U.S. National Center for Health Statistics National Health Interview Survey and linked them to files from the National Death Index to determine mortality rates. Included were more than 147,000 respondents aged between 18 and 84 years who did not have Medicaid. Among these individuals, 5.9% were cancer survivors. The concern for cancer survivors with these plans is that in addition to recurrence that could require costly treatments, there might be issues related to survivorship. Investigators found that overall survival was worse for those with a cancer diagnosis coupled with high-deductible health insurance, with a hazard ratio of nearly 1.5.
But when the researchers reviewed data from the general population without a history of cancer, they didn't find any association between high-deductible health insurance and outcomes. According to Dr. Barnes, the leading hypothesis is that patients with cancer who have a high-deductible plan delay workup for a potential new or recurrent cancer diagnosis or postpone or avoid other care. The results also indicated that survival among certain subgroups, such as non-Hispanic white patients, patients with higher incomes, and patients with at least a college or high school education, was worse for those with a high-deductible health plan, not the groups who are typically impacted by care disparities. It is possible that these individuals are more likely to select high-deductible health plans and that having these plans might counteract what might otherwise be adequate access to care.
A key take-home from this analysis is that cancer patients and survivors, whatever their racial, ethnic, or socioeconomic status, should have access to health plans with low deductibles and should be informed of the potential risks of their long-term health and survival when covered by high-deductible plans.
Join me again tomorrow to hear more top takeaways from ASCO24. If you value the insights that you hear on the ASCO Daily News Podcast, please remember to rate, review and subscribe wherever you get your podcasts.
Disclaimer:
The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity or therapy should not be construed as an ASCO endorsement.
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Disclosures:
Dr. John Sweetenham:
Consulting or Advisory Role: EMA Wellness