Latest news with #ctDNA
Yahoo
06-06-2025
- Business
- Yahoo
Burning Rock Reports First Quarter 2025 Financial Results
GUANGZHOU, China, June 06, 2025 (GLOBE NEWSWIRE) -- Burning Rock Biotech Limited (NASDAQ: BNR, the 'Company' or 'Burning Rock'), a company focused on the application of next generation sequencing (NGS) technology in the field of precision oncology, today reported financial results for the three months ended March 31, 2025. Recent Business Updates Therapy Selection and MRD Personalized Minimal Residual Disease (MRD) product, CanCatch® Custom supports advancement in oesophageal squamous cell carcinoma（OSCC）treatment, with results published in the Molecular Cancer in May 2025. The study is a two-arm, multicenter, randomized, double-blind phase 2 study, comparing the efficacy of systemic treatment combining nCT with immunotherapy against nCT alone for OSCC patients. The study demonstrates that Perioperative Nivolumab plus chemotherapy is a viable and safe option for systemically treating locally advanced resectable OSCC, and monitoring minimal residual disease through ctDNA could be potentially valuable for assessing the effectiveness of adjuvant therapy and for prognostic evaluation in a systemic manner. Presented study results on non-small cell lung cancer and gastrointestinal stromal tumor (GIST) at the ASCO in June 2025. 'Personalized tumor-informed ctDNA has the potential to inform recurrence in high-risk locally advanced stage GIST patients, especially for patients with irregular adjuvant therapy' and 'MUSETALK-Lung01 (MUltiomics SEquencing Technique AppLication Kick-start) is a prospective, longitudinal, observational study designed to evaluate the clinical utility of a tumor-naïve ctDNA assay in patients with early-stage non-small cell lung cancer (NSCLC).' Presented multiple study results at the 2025 AACR in April, showcasing the clinical utility of the tumor-informed personalized MRD assay (CanCatch® Custom) and the tumor-naïve methylation-based MRD assay. First Quarter 2025 Financial Results Revenues were RMB133.1 million (US$18.3 million) for the three months ended March 31, 2025, representing a 5.9% increase from RMB125.6 million for the same period in 2024. Revenue generated from central laboratory business was RMB38.3 million (US$5.3 million) for the three months ended March 31, 2025, representing a 19.6% decrease from RMB47.6 million for the same period in 2024, primarily attributable to a decrease in the number of tests, as we continued to focus on our in-hospital business. Revenue generated from in-hospital business was RMB57.7 million (US$7.9 million) for the three months ended March 31, 2025, representing a 0.5% increase from RMB57.4 million for the same period in 2024, driven by a continuous growth in sales volume. Revenue generated from pharma research and development services was RMB37.1 million (US$5.1 million) for the three months ended March 31, 2025, representing a 79.9% increase from RMB20.6 million for the same period in 2024, primarily attributable to increased development and testing services performed for our pharma customers, and several milestones of our pharma programs were achieved. Cost of revenues was RMB35.7 million (US$4.9 million) for the three months ended March 31, 2025, representing a 10.6% decrease from RMB39.9 million for the same period in 2024, primarily due to a decrease in cost of central laboratory business, which was in line with the decrease in revenue generated from this business. Gross profit was RMB97.4 million (US$13.4 million) for the three months ended March 31, 2025, representing a 13.7% increase from RMB85.7 million for the same period in 2024. Gross margin was 73.2% for the three months ended March 31, 2025, compared to 68.2% for the same period in 2024. By channel, gross margin of central laboratory business was 84.1% for the three months ended March 31, 2025, compared to 77.7% during the same period in 2024, primarily due to a reduction in material and labor costs resulted from cost optimization and control measures and a decreased depreciation and rental cost in relation to our laboratory of Guangzhou headquarter; gross margin of in-hospital business was 76.1% for the three months ended March 31, 2025, compared to 68.3% during the same period in 2024, primarily due to the same reason; gross margin of pharma research and development services was 57.5% for the three months ended March 31, 2025, compared to 46.1% during the same period of 2024, primarily due to the cost optimization measures and an increase in test volume of higher margin projects. Non-GAAP gross profit, which excludes depreciation and amortization expenses, RMB100.7 million (US$13.9 million) for the three months ended March 31, 2025, representing an 8.3% increase from RMB93.0 million for the same period in 2024. Non-GAAP gross margin was 75.6% for the three months ended March 31, 2025, compared to 74.0% for the same period in 2024. Operating expenses were RMB112.6 million (US$15.5 million) for the three months ended March 31, 2025, representing a 46.8% decrease from RMB211.5 million for the same period in 2024. The decrease was primarily driven by budget control measures and headcount reduction to improve the Company's operating efficiency. Research and development expenses were RMB40.4 million (US$5.6 million) for the three months ended March 31, 2025, representing a 38.8% decrease from RMB66.0 million for the same period in 2024, primarily due to (i) a decrease in amortized expense on share-based compensation; (ii) a decrease in the expenditure for detection research and (iii) a decrease in depreciation and amortization. Selling and marketing expenses were RMB40.9 million (US$5.6 million) for the three months ended March 31, 2025, representing a 12.7% decrease from RMB46.9 million for the same period in 2024, primarily due to (i) a decrease in staff cost resulted from the reorganization of our sales department to improve operating efficiency and (ii) a decrease in depreciation and amortization. General and administrative expenses were RMB31.3 million (US$4.3 million) for the three months ended March 31, 2025, representing a 68.3% decrease from RMB98.7 million for the same period in 2024, primarily due to (i) a decrease in amortized expense on share-based compensation; (ii) a decrease in depreciation and amortization; (iii) a decrease in staff cost resulted from the reorganization; and (iv) a decrease in operating lease expense for office building. Net loss was RMB13.5 million (US$1.9 million) for the three months ended March 31, 2025, compared to RMB121.5 million for the same period in 2024. Cash, cash equivalents and restricted cash were RMB497.4 million (US$68.5 million) as of March 31, 2025. Exchange Rate Information This press release contains translations of certain Renminbi amounts into U.S. dollars at a specified rate solely for the convenience of the reader. Unless otherwise noted, all translations from Renminbi to U.S. dollars and from U.S. dollars to Renminbi are made at a rate of RMB7.2567 to US$1.00, the exchange rate on March 31, 2025, set forth in the H.10 statistical release of the Federal Reserve Board. The Company makes no representation that the Renminbi or U.S. dollars amounts referred could be converted into U.S. dollars or Renminbi, as the case may be, at any particular rate or at all. About Burning Rock Burning Rock Biotech Limited (NASDAQ: BNR), whose mission is to guard life via science, focuses on the application of next generation sequencing (NGS) technology in the field of precision oncology. Its business consists of i) NGS-based therapy selection testing for late-stage cancer patients, and ii) cancer early detection, which has moved beyond proof-of-concept R&D into the clinical validation stage. For more information about Burning Rock, please visit: Safe Harbor Statement This press release contains forward-looking statements. These statements constitute 'forward-looking' statements within the meaning of Section 21E of the Securities Exchange Act of 1934, as amended, and as defined in the U.S. Private Securities Litigation Reform Act of 1995. These forward-looking statements can be identified by terminology such as 'will,' 'expects,' 'anticipates,' 'future,' 'intends,' 'plans,' 'believes,' 'estimates,' 'target,' 'confident' and similar statements. Burning Rock may also make written or oral forward-looking statements in its periodic reports to the SEC, in its annual report to shareholders, in press releases and other written materials and in oral statements made by its officers, directors or employees to third parties. Statements that are not historical facts, including statements about Burning Rock's beliefs and expectations, are forward-looking statements. Such statements are based upon management's current expectations and current market and operating conditions, and relate to events that involve known or unknown risks, uncertainties and other factors, all of which are difficult to predict and many of which are beyond Burning Rock's control. Forward-looking statements involve risks, uncertainties and other factors that could cause actual results to differ materially from those contained in any such statements. All information provided in this press release is as of the date of this press release, and Burning Rock does not undertake any obligation to update any forward-looking statement as a result of new information, future events or otherwise, except as required under applicable law. Non-GAAP Measures In evaluating the business, the Company considers and uses non-GAAP measures, such as non-GAAP gross profit and non-GAAP gross margin, as supplemental measures to review and assess operating performance. The presentation of these non-GAAP financial measures is not intended to be considered in isolation or as a substitute for the financial information prepared and presented in accordance with accounting principles generally accepted in the United States of America ('U.S. GAAP'). The company defines non-GAAP gross profit as gross profit excluding depreciation and amortization. The company defines non-GAAP gross margin as gross margin excluding depreciation and amortization. The company presents these non-GAAP financial measures because they are used by management to evaluate operating performance and formulate business plans. The company believe non-GAAP gross profit and non-GAAP gross margin excluding non-cash impact of depreciation and amortization reflect the company's ongoing business operations in a manner that allows more meaningful period-to-period comparisons. Contact: IR@ Selected Operating Data As of March 31, 2024 June 30, 2024 September 30, 2024 December 31, 2024 March 31, 2025 In-hospital Channel: Pipeline partner hospitals(1) 28 29 30 29 30 Contracted partner hospitals(2) 59 59 61 63 63 Total number of partner hospitals 87 88 91 92 93(1) Refers to hospitals that are in the process of establishing in-hospital laboratories, laboratory equipment procurement or installation, staff training or pilot testing using the Company's products. (2) Refers to hospitals that have entered into contracts to purchase the Company's products for use on a recurring basis in their respective in-hospital laboratories the Company helped them establish. Kit revenue is generated from contracted hospitals. Selected Financial Data For the three months ended Revenues March 31, 2024 June 30, 2024 September 30, 2024 December 31, 2024 March 31, 2025 (RMB in thousands) Central laboratory channel 47,614 48,773 39,984 39,278 38,296 In-hospital channel 57,387 59,872 63,769 43,464 57,687 Pharma research and development channel 20,622 26,888 24,891 43,280 37,099 Total revenues 125,623 135,533 128,644 126,022 133,082 For the three months ended Gross profit March 31,2024 June 30,2024 September 30,2024 December 31,2024 March 31,2025 (RMB in thousands) Central laboratory channel 37,002 38,424 33,262 33,153 32,191 In-hospital channel 39,192 44,058 46,580 29,563 43,895 Pharma research and development channel 9,500 12,956 12,004 26,706 21,315 Total gross profit 85,694 95,438 91,846 89,422 97,401 For the three months ended Share-based compensation expenses March 31,2024 June 30,2024 September 30,2024 December 31,2024 March 31,2025 (RMB in thousands) Cost of revenues 596 464 289 520 308 Research and development expenses 12,287 12,008 3,180 3,202 1,800 Selling and marketing expenses 508 1,232 1,917 1,353 1,025 General and administrative expenses 55,990 54,407 4,732 2,937 1,413 Total share-based compensation expenses 69,381 68,111 10,118 8,012 4,546 Burning Rock Biotech Limited Unaudited Condensed Statements of Comprehensive Loss (in thousands, except for number of shares and per share data) For the three months ended March 31,2024 June 30,2024 September 30, 2024 December 31,2024 March 31, 2025 March 31, 2025 RMB RMB RMB RMB RMB US$ Revenues 125,623 135,533 128,644 126,022 133,082 18,340 Cost of revenues (39,929 ) (40,095 ) (36,798 ) (36,600 ) (35,681 ) (4,918 ) Gross profit 85,694 95,438 91,846 89,422 97,401 13,422 Operating expenses: Research and development expenses (65,985 ) (64,952 ) (49,150 ) (52,203 ) (40,389 ) (5,566 ) Selling and marketing expenses (46,856 ) (48,907 ) (48,411 ) (46,730 ) (40,888 ) (5,635 ) General and administrative expenses (98,681 ) (92,794 ) (32,874 ) (37,289 ) (31,303 ) (4,314 ) Impairment loss on long-lived assets (35,127 ) Total operating expenses (211,522 ) (206,653 ) (130,435 ) (171,349 ) (112,580 ) (15,515 ) Loss from operations (125,828 ) (111,215 ) (38,589 ) (81,927 ) (15,179 ) (2,093 ) Interest income 4,038 3,187 3,173 1,814 2,581 356 Other income (expense), net 434 (82 ) 1 4,353 (652 ) (90 ) Foreign exchange (loss) gain, net (13 ) 262 (129 ) (220 ) (26 ) (4 ) Loss before income tax (121,369 ) (107,848 ) (35,544 ) (75,980 ) (13,276 ) (1,831 ) Income tax expenses (180 ) (190 ) (201 ) (5,314 ) (224 ) (31 ) Net loss (121,549 ) (108,038 ) (35,745 ) (81,294 ) (13,500 ) (1,862 ) Net loss attributable to Burning Rock Biotech Limited's shareholders (121,549 ) (108,038 ) (35,745 ) (81,294 ) (13,500 ) (1,862 ) Net loss attributable to ordinary shareholders (121,549 ) (108,038 ) (35,745 ) (81,294 ) (13,500 ) (1,862 ) Loss per share for class A and class B ordinary shares: Class A ordinary shares - basic and diluted (1.19 ) (1.05 ) (0.35 ) (0.79 ) (0.13 ) (0.02 ) Class B ordinary shares - basic and diluted (1.19 ) (1.05 ) (0.35 ) (0.79 ) (0.13 ) (0.02 ) Weighted average shares outstanding used in loss per share computation: Class A ordinary shares - basic and diluted 85,219,188 85,271,858 85,902,670 86,036,286 90,291,658 90,291,658 Class B ordinary shares - basic and diluted 17,324,848 17,324,848 17,324,848 17,324,848 17,324,848 17,324,848 Other comprehensive income (loss), net of tax of nil: Foreign currency translation adjustments 590 940 (4,054 ) 6,009 (72 ) (10 ) Total comprehensive loss (120,959 ) (107,098 ) (39,799 ) (75,285 ) (13,572 ) (1,872 ) Total comprehensive loss attributable to Burning Rock Biotech Limited's shareholders (120,959 ) (107,098 ) (39,799 ) (75,285 ) (13,572 ) (1,872 ) Burning Rock Biotech LimitedUnaudited Condensed Consolidated Balance Sheets(In thousands) As of December 31, 2024 March 31,2025 March 31,2025 RMB RMB US$ ASSETS Current assets: Cash and cash equivalents 519,849 495,145 68,233 Restricted cash 2,313 2,261 312 Accounts receivable, net 152,013 159,463 21,974 Contract assets, net 13,855 17,178 2,367 Inventories, net 62,625 65,424 9,016 Prepayments and other current assets, net 25,963 22,072 3,042 Total current assets 776,618 761,543 104,944 Non-current assets: Property and equipment, net 47,152 41,162 5,672 Operating right-of-use assets 53,188 43,804 6,036 Intangible assets, net 421 386 53 Other non-current assets 7,926 7,822 1,078 Total non-current assets 108,687 93,174 12,839 TOTAL ASSETS 885,305 854,717 117,783 Burning Rock Biotech LimitedUnaudited Condensed Consolidated Balance Sheets (Continued)(in thousands) As of December 31,2024 March 31,2025 March 31,2025 RMB RMB US$ LIABILITIES AND SHAREHOLDERS' EQUITY Current liabilities: Accounts payable 33,747 35,938 4,952 Deferred revenue 117,895 117,200 16,151 Accrued liabilities and other current liabilities 89,498 76,198 10,501 Customer deposits 592 592 82 Current portion of operating lease liabilities 24,567 22,524 3,104 Total current liabilities 266,299 252,452 34,790 Non-current liabilities: Non-current portion of operating lease liabilities 27,754 19,814 2,730 Other non-current liabilities 10,425 10,649 1,467 Total non-current liabilities 38,179 30,463 4,197 TOTAL LIABILITIES 304,478 282,915 38,987 Shareholders' equity: Class A ordinary shares 124 124 17 Class B ordinary shares 21 21 3 Additional paid-in capital 5,002,255 5,005,991 689,844 Treasury stock (63,264 ) (62,453 ) (8,606 ) Accumulated deficits (4,200,261 ) (4,213,761 ) (580,672 ) Accumulated other comprehensive loss (158,048 ) (158,120 ) (21,790 ) Total shareholders' equity 580,827 571,802 78,796 TOTAL LIABILITIES AND SHAREHOLDERS' EQUITY 885,305 854,717 117,783 Burning Rock Biotech LimitedUnaudited Condensed Statements of Cash Flows(in thousands) For the three months ended March 31,2024 March 31,2025 March 31,2025 RMB RMB US$ Net cash generated from (used in) operating activities 19,062 (23,527 ) (3,242 ) Net cash used in investing activities (812 ) (1,531 ) (211 ) Net cash used in financing activities (74 ) - - Effect of exchange rate on cash, cash equivalents and restricted cash 5,739 302 43 Net increase in (decrease) cash, cash equivalents and restricted cash 23,915 (24,756 ) (3,410 ) Cash, cash equivalents and restricted cash at the beginning of period 498,247 522,162 71,955 Cash, cash equivalents and restricted cash at the end of period 522,162 497,406 68,545 Burning Rock Biotech LimitedReconciliations of GAAP and Non-GAAP Results For the three months ended March 31,2024 June 30,2024 September 30,2024 December 31,2024 March 31,2025 (RMB in thousands) Gross profit: Central laboratory channel 37,002 38,424 33,262 33,153 32,191 In-hospital channel 39,192 44,058 46,580 29,563 43,895 Pharma research and development channel 9,500 12,956 12,004 26,706 21,315 Total gross profit 85,694 95,438 91,846 89,422 97,401 Add: depreciation and amortization: Central laboratory channel 1,919 1,226 1,277 1,010 562 In-hospital channel 1,524 824 798 623 290 Pharma research and development channel 3,856 4,417 3,846 2,534 2,412 Total depreciation and amortization included in cost of revenues 7,299 6,467 5,921 4,167 3,264 Non-GAAP gross profit： Central laboratory channel 38,921 39,650 34,539 34,163 32,753 In-hospital channel 40,716 44,882 47,378 30,186 44,185 Pharma research and development channel 13,356 17,373 15,850 29,240 23,727 Total non-GAAP gross profit 92,993 101,905 97,767 93,589 100,665 Non-GAAP gross margin： Central laboratory channel 81.7% 81.3% 86.4% 87.0% 85.5% In-hospital channel 70.9% 75.0% 74.3% 69.5% 76.6% Pharma research and development channel 64.8% 64.6% 63.7% 67.6% 64.0% Total non-GAAP gross margin 74.0% 75.2% 76.0% 74.3% 75.6%Error in retrieving data Sign in to access your portfolio Error in retrieving data Error in retrieving data Error in retrieving data Error in retrieving data
Medscape
05-06-2025
- Business
- Medscape
Could Liquid Biopsy Guide Treatment in Cervical Cancer?
Circulating tumor DNA (ctDNA) levels in patients with cervical cancer before and during treatment were prognostic of disease progression and survival in a post hoc analysis of the phase 3 CALLA trial. The findings 'support the future utility of…ctDNA analysis to help guide treatment decisions for locally advanced cervical cancer,' said lead study author Jyoti Mayadev, MD, a radiation oncologist at Moores NCI-Designated Comprehensive Cancer Center and professor of radiation medicine and applied sciences at the University of California, San Diego School of Medicine in La Jolla, California. Mayadev reported the results at the American Society of Clinical Oncology (ASCO) 2025 annual meeting. They were published simultaneously in the Annals of Oncology . The previously published CALLA trial showed that patients receiving adjuvant chemoradiotherapy (CRT) for locally advanced cervical cancer did not have improved progression-free survival (PFS) with the addition of concurrent durvalumab compared with placebo. The trial included 770 patients with previously untreated stage IB2-IIB node-positive or IIIA-IVA any node-status locally advanced cervical cancer who were randomly assigned to receive durvalumab (1500 mg intravenously once every 4 weeks) plus CRT (n = 385) or CRT alone (n = 385). CRT, consisting of external beam radiotherapy with intravenous cisplatin or carboplatin, was delivered once weekly for 5 weeks, followed by image-guided brachytherapy. Exploratory Analysis Methods and Results A preplanned exploratory analysis sampled ctDNA levels in a subset of 186 patients to determine if ctDNA could serve as a biomarker for treatment response. The study used an ultrasensitive tumor-informed ctDNA assay, personalized for each patient, to test plasma at baseline, cycle 3 day 1 (immediately post-CRT), and cycle 6 day 1 (3 months post-CRT), explained Mayadev during her presentation at the meeting. ctDNA was detected in 99% of baseline samples, with no difference across the treatment arms, she reported. Immediately after treatment, detectable levels decreased to 35.5% in the durvalumab/CRT arm and 39.8% in the CRT-only arm. By 3 months after treatment, levels declined further to 23.4% and 36.4%, respectively, demonstrating a 13% lower rate of detectable ctDNA in the durvalumab/CRT arm at this timepoint. The study showed that ctDNA levels were prognostic of both PFS and overall survival (OS), regardless of treatment arm. Among patients in whom ctDNA was detectable immediately posttreatment, 68% subsequently progressed, and among those without detectable ctDNA, 83% had not progressed by the time of data cutoff, for a positive predictive value of 61%, a negative predictive value of 83%, and a sensitivity and specificity of 68% and 78%, respectively. ctDNA Detected 5.5 Months Before Radiographic Progression The median lead time from ctDNA detection on the ultrasensitive assay until radiographic or clinical evidence of progression was 5.5 months, ranging from 1.5 to 16.5 months. Looking specifically at PFS and OS, patients with ctDNA levels were prognostic of PFS and OS for patients in both treatment arms at all timepoints measured. In the durvalumab/CRT arm, low vs high ctDNA at baseline conferred a hazard ratio of 0.60 for PFS and of 0.63 for OS. In the CRT-only arm, low vs high ctDNA conferred hazard ratios of 0.62 and 0.85 for PFS and OS, respectively. Similarly, detectable ctDNA levels immediately posttreatment compared with undetectable levels identified patients at a higher risk for progression and death, regardless of treatment arm. With detectable ctDNA as the reference, PFS and OS hazard ratios were 0.23 and 0.20 in the durvalumab/CRT arm and 0.15 and 0.18 in the CRT-only arm, respectively. Having no ctDNA detected 3 months after treatment cessation reduced the risks for progression and death by at least 95% for patients in both treatment arms, Mayadev said during her presentation. Multivariate analysis showed that detection of ctDNA immediately posttreatment conferred a hazard ratio of 5.27 ( P < .001) for PFS, independent of disease stage at baseline or treatment allocation, she said. 'Our study found that persistent ctDNA levels posttreatment strongly correlated with an increased risk of relapse and were likely reflective of residual disease that, in some instances, went undetected by other means,' wrote Mayadev and co-authors in their paper. 'On average, ctDNA was detected 5.5 months before radiographic progression. In clinical practice, this could allow for proactive treatment management to potentially improve patient outcomes — for example, earlier consideration of adjuvant therapies, such as immunotherapy or systemic therapy, or a switch to a novel therapeutic regimen. In cases of recurrence, tracking ctDNA levels in real-time could also help assess response to salvage therapy, providing a dynamic tool for optimizing therapeutic decisions.' 'This really is a good analysis showing how ctDNA is definitely a better prognostic marker than standard poor prognostic clinical factors such as nodal status and even updated FIGO staging for cervical cancer,' said Mark Einstein, MD, the discussant for the paper, who is professor and chair of the Department of Obstetrics and Gynecology and Women's Health at Montefiore Medical Center/Albert Einstein College of Medicine, New York City. However, he said the positive predictive value and sensitivity 'are good, but they're not great. The negative predictive value, though, is excellent, and this would reveal that the test might have some value as a negative predictive marker of recurrence rather than a positive predictive marker of recurrence.' But, the bigger question, he said, is 'what are we going to do with that information? If we actually do know that someone has a positive ctDNA, are we going to get into the situation that we are in with ovary cancer, with CA125 without measurable disease, where it just creates a lot of anxiety without necessarily restarting treatment? This could identify central disease before it actually becomes distant, which could lead to potentially curative surgical options, and it might put someone on increased surveillance in imaging, but I think we need to really look at this prospectively.' Also commenting on the study, Sarah Kim, MD, a gynecologic surgeon specializing in the treatment of ovarian, endometrial, cervical, vulvar, and vaginal cancer at the Memorial Sloan Kettering Cancer Center in New York City, pointed out what she found useful and what additional questions need to be answered. 'Further studies need to be done to validate these results and determine the clinical utility in the setting of adjuvant therapy or recurrence,' she said in an interview with Medscape Medical News . 'I think these are important findings and potentially clinically impactful for patients with locally advanced cervical cancer,' said Kim. 'They support the use of ctDNA to detect minimal residual disease and/or the use of ctDNA as a prognostic marker, which is lacking in cervical cancer. We have seen similar results in patients with endometrial cancer, where the ctDNA increases prior to any detection of disease on imaging.' The trial was sponsored by AstraZeneca. Mayadev disclosed leadership roles with the American Brachytherapy Society and NRG Oncology; honoraria from AstraZeneca; consulting or advisory roles with Agenus, AstraZeneca/MedImmune, Merck, Primmune Therapeutics, and Varian Medical Systems; research funding from Varian Medical Systems; and travel, accommodations, and other expenses from Merck. Einstein disclosed a consulting or advisory role with Antiva Biosciences, Asieris Pharmaceuticals, and Merck, and research funding from Johnson & Johnson, Merck, and PapiVax Biotech, Inc. Kim had no disclosures.
Medscape
05-06-2025
- Business
- Medscape
Catching Resistance Early: Can New Breast Cancer Drug Help?
CHICAGO — Can spotting an emerging ESR1 mutation early and changing first-line drugs before progression improve outcomes in patients with hormone receptor (HR)–positive, human epidermal growth factor receptor 2–negative advanced breast cancer? Interim findings from the SERENA-6 trial suggest that may be the case. Patients who switched from a first-line aromatase inhibitor to camizestrant, an investigational next-generation oral selective estrogen-receptor degrader, at the first signs of an emerging ESR1 mutation demonstrated significantly improved progression-free survival compared with those who continued their initial regimen. Notably, circulating tumor DNA (ctDNA) testing allowed investigators to identify ESR1 mutations, which emerge at the time of disease progression in about 40% of patients on a first-line aromatase inhibitor and lead to treatment resistance. Camizestrant, which has shown activity in patients who develop ESR1 mutations, helped improve first-line outcomes and has 'potential to become a new treatment strategy,' according to co-principal investigator Nicholas Turner, MD, PhD, professor and honorary consultant in medical oncology at the Institute of Cancer Research and Royal Marsden Hospital, London, England, who presented the findings at the American Society of Clinical Oncology (ASCO) 2025 annual meeting. Results were simultaneously published in The New England Journal of Medicine . This trial also demonstrated 'the clinical utility of ctDNA monitoring to detect and treat emerging resistance in breast cancer,' said Turner. While praising the findings, others were not convinced that the SERENA-6 results warrant a change in practice yet. 'Based on first-line progression-free survival alone, this could represent a new regulatory approval path,' said invited discussant Angela DeMichele, MD, of the University of Pennsylvania, Philadelphia. But, DeMichele cautioned, 'I cannot recommend the SERENA-6 strategy at this time.' One key reason, DeMichele noted, is that it's too early to tell whether this strategy improves overall survival. If camizestrant is approved based on progression-free survival and quality of life, DeMichele wondered, is it worth going through the ctDNA testing process if the drug doesn't help patients live longer? Paolo Tarantino, MD, a breast oncologist at Dana-Farber Cancer Institute and Harvard Medical School in Boston, echoed this sentiment in a tweet on X: 'Outstanding results, though not ready for clinical practice (yet),' adding that it will also be 'important to take into account financial, psychological, and systemic costs of the strategy.' Using ctDNA to Track Resistance In the study, 3256 patients who had received at least 6 months of treatment with aromatase inhibitors and CDK4/6 therapy (palbociclib, ribociclib, or abemaciclib) received ctDNA testing with Guardant360 CDx every 2-3 months at the time of routine staging exams. Overall, 315 patients who had an ESR1 mutation detected and had no radiologic evidence of disease progression were randomly assigned to either switch from the aromatase inhibitor to 75 mg of camizestrant daily (n = 157) or continue their aromatase inhibitor/CDK4/6 regimen (n = 158). (An additional 233 patients who had an ESR1 mutation detected were not included for a variety of reasons, including disease progression and consent withdrawal.) At the planned interim analysis, the median progression-free survival was 16.0 months in the camizestrant group and 9.2 months in the aromatase inhibitor group (adjusted hazard ratio [aHR], 0.44; P < .00001). At 24 months, only 5.4% of patients who had continued their initial first-line treatment had not progressed compared with 30% of patients on camizestrant. The progression-free survival findings were consistent across clinically relevant patient subgroups. Patients who switched to camizestrant also showed improved time to deterioration in global health status and quality of life — a median of 23.0 months vs 6.4 months in the aromatase group (aHR, 0.53). At the time of the interim analysis, overall survival data were immature, with 20 deaths in the camizestrant group and 19 in the aromatase inhibitor group (HR, 0.91; 95% CI, 0.48-1.73). As for time to second progression, there were 38 events in the camizestrant group and 47 events in the aromatase group, but the findings were also immature. As for adverse events, 60% of patients in the camizestrant group had a grade 3 or higher event, 10% of which were deemed serious compared with 46% in the aromatase group, 12% of which were serious. Neutropenia (45% vs 34%, respectively) and anemia (5% in both groups) were the most common grade 3 or higher adverse events. Only 1% of patients on camizestrant discontinued treatment due to adverse events. Overall, Turner concluded that 'for people with HR-positive advanced breast cancer, the results of SERENA-6 show that camizestrant plus CDK4/6 inhibitor could be a new treatment option to use at the point of ESR1 mutation detection during treatment with first-line aromatase inhibitor plus CDK4/6 inhibitor — but before the cancer grows.' Despite the promising findings, DeMichele highlighted several key unanswered questions and challenges. Notably, will this strategy lead to longer overall survival and demonstrate clinical utility? Overall survival and time to second progression are currently not known, DeMichele said. The trial did not address whether first-line treatment gains would be lost if camizestrant was given in the second-line setting after anatomic progression. DeMichele also noted the high cost and potential anxiety associated with serial ctDNA testing. Overall, 'the full complement of financial, psychological, and systemic costs is needed to fully assess utility and feasibility for implementation,' she added. SERENA-6 was supported by AstraZeneca. Turner disclosed consulting or advisory roles with AstraZeneca, Exact Sciences, Gilead Sciences, GlaxoSmithKline, Guardant Health, Inivata Lilly, Merck Sharp & Dohme, Novartis, Pfizer, Relay Therapeutics, Repare Therapeutics, and Roche. DeMichele disclosed a consulting or advisory role with Pfizer.
Yahoo
05-06-2025
- Health
- Yahoo
Carlisle Mum gets earlier cancer treatment thanks to 'revolutionary' blood test
A mother-of-two from Carlisle says she has been given her life back after receiving targeted cancer treatment. Rebeca Proctor, 41, from Carlisle, was diagnosed with stage 4 non-small-cell lung cancer in January. She was able to begin treatment earlier thanks to a new NHS liquid biopsy blood test, which identified a specific genetic mutation. Ms Proctor said: "When I found out I had stage 4 cancer it felt like I'd been punched in the gut, I was scared – I just thought about my children, and if I would get to see my little girl start nursery, and how I would explain my diagnosis to my children – it was just heart-breaking to think about. "But the medication has given me my life back and my kids have got their mum back. "I'm taking it day by day and for now the treatment is doing what it's meant to be doing and shrinking the tumour, and I've got my energy back. "I know I'm not going to be cured but I've come to terms with my diagnosis and the pills are stopping my cancer cells from spreading – we'll keep fighting this and dealing with what's been thrown at us." The liquid biopsy revealed she had an ALK genetic mutation, allowing her to start a targeted therapy, brigatinib. A traditional tissue biopsy confirmed the result around 10 days later. Ms Proctor is under the care of Dr Sally Hall, a consultant medical oncologist at the Northern Centre for Cancer Care in North Cumbria. The new blood test, now available across the NHS in England, detects fragments of tumour DNA in the bloodstream. It identifies genetic mutations that can guide personalised cancer treatment. NHS England recently announced that up to 15,000 patients with suspected lung cancer could benefit from the test each year. An NHS pilot found that lung cancer patients could start targeted treatment up to 16 days sooner using the liquid biopsy compared to standard tissue biopsies. The pilot also showed that some patients were able to avoid unnecessary chemotherapy and its side effects, improving their quality of life. Professor Peter Johnson, NHS national clinical director for cancer, said: "Liquid biopsies are leading us into a new era of personalised cancer care and it's fantastic that we are now able to expand the use of this revolutionary test on the NHS to help tailor treatment for thousands of patients across the country. "Cutting-edge genomic testing is helping us deliver more targeted and kinder care for patients, enabling some to avoid more intensive treatments such as further chemotherapy, which can have a huge impact." Professor Alastair Greystoke, co-clinical lead of the ctDNA pilot and honorary medical oncologist at Newcastle Hospitals, said: "This is the first ever national implementation of a 'liquid biopsy first' approach to the diagnosis and treatment of a cancer." "Not only has it led to faster and more precise treatment for patients with lung cancer, but we have also been able to show that this is a cost-effective measure for the NHS and set up the framework to evaluate this in other cancers going forward." Professor Dame Sue Hill, chief scientific officer for England, said: "This represents a real step-change in care for eligible lung and breast cancer patients on the NHS. "The liquid biopsy testing enables genomic mutations in the fragments of cancer that enter the bloodstream of these patients to be detected. "This testing is transforming care and helping clinicians match patients earlier, especially when cancer tissue may not be available, with potentially life-extending targeted therapies rapidly and with greater precision."
Medscape
01-06-2025
- Health
- Medscape
Can New Biomarker Help Identify High-Risk DLBCL Patients?
For patients with diffuse large B-cell lymphoma (DLBCL), the detection of circulating tumor DNA (ctDNA) following first-line treatment is independently predictive of disease recurrence and overall survival over 2 years, suggesting important prognostic value of the biomarker to improve upon standard assessment with PET-CT imaging. 'We demonstrated the prognostic value of ctDNA MRD [minimal residual disease] in first-line DLBCL cell patients [and that] ctDNA MRD provides independent evidence of residual disease beyond PET-CT,' said first author Steven Wang, MD, of Amsterdam UMC Location Vrije Universiteit, Amsterdam, the Netherlands, in presenting the findings at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting. 'These results support the integration of ctDNA MRD as a standard component of response evaluation in first-line DLBCL treatment,' he said. The prognosis for long-term outcomes in DLBCL currently relies on PET-CT; however, key challenges with the approach include sometimes suboptimal sensitivity and specificity, with the potential to miss microscopic residual disease. Liquid biopsy-based analysis of ctDNA, increasingly used in other cancers, meanwhile offers a radiation-free, non-invasive method for the assessment and monitoring of DLBCL. To further investigate the biomarker's prognostic benefits in DLBCL in a prospective context, Wang and colleagues evaluated data on 160 patients at more than 50 centers in the Netherlands and Belgium in the HOVON-902 trial. Of the patients, most (79%) had stage 3 or 4 disease. All patients had been treated with curative-intent first-line therapy, with either R-CHOP or DA-EPOCH-R chemotherapy regimens. In the assessment of ctDNA MRD, the investigators utilized the phased variant (PV) enrichment and detection sequencing (PhasED-Seq) assay, which targets unique 'phased variant' alterations, or multiple mutations on the same DNA molecule. The design boosts the assay's sensitivity compared with other tests, which can have limitations such as error profiles of single nucleotide variants (SNVs). Among the patients, most (90%) had DLBCL, with 9% having high-grade B-cell lymphoma and 1% with primary mediastinal large B-cell lymphoma. In terms of the distribution of International Prognostic Index (IPI) risk level, 22% were low-risk, 29% low-intermediate risk, 27% high-intermediate risk, and 22% at high-risk. Patients' median age was 67.5 years. With 31 months of median follow-up in the cohort overall, the 24-month rates of progression-free survival (PFS) and overall survival (OS) were 74% and 86%, respectively. The rates of PFS after 3 years were substantially higher for those who were MRD-negative at the end of treatment compared with those who were MRD-positive (85% vs 15%, respectively; hazard ratio [HR] 11.03; P < .0001), and 3-year rates of OS were also higher (92% vs 41%; HR, 7.38; P < .0001). The findings show that 'end-of-treatment ctDNA MRD is strongly prognostic for PFS and OS,' Wang said. Higher cancer stage and IPI risk were associated with MRD positivity (both P < .05), and ctDNA was the most strongly prognostic of PFS (HR, 11.03), compared with end-of-treatment PET-CT results (HR, 5.31) or IPI level of risk (HR, 1.61). Of patients who did not have a complete response based on PET results, MRD-positivity was likewise significantly prognostic for worse PFS at 3 years (PFS 4%) compared with those who were MRD-negative (PFS 64%), importantly suggesting the ability of MRD to adjudicate imaging results (HR for PFS, 6.78; P < .0001). 'End of treatment ctDNA MRD-positivity in patients without complete response have especially poor outcomes,' Wang noted. All of the patients who did not achieve a complete molecular response and remained MRD-positive experienced a relapse. The prognostic accuracy of ctDNA-MRD status was observed across subgroups, including based on the source of baseline sample (tumor vs plasma), best clinical response, IPI, sex, lactate dehydrogenase, stage, or extranodal disease. The researchers also examined how ctDNA MRD status at the end of treatment correlated with the timing of response, and they found that 80% of patients who relapsed within a year of treatment had positive ctDNA MRD at the end of treatment, while only 22% of patients who relapsed after the first 12 months of first-line therapy had positive MRD. 'This distinction is important as early relapsers might be eligible for CAR T-cell therapy, and this demonstrates that end of treatment ctDNA MRD can reliably predict early relapses; however, long late relapses might require longitudinal MRD monitoring,' Wang explained. 'These data demonstrate the robust prognostic value of ctDNA MRD by PhasED-Seq in first-line DLBCL patients,' Wang said. ctDNA Risk-Stratification Benefits Important Discussing the research at the meeting, Mark Roschewski, MD, of the National Cancer Institute, Bethesda, Maryland, agreed that results on the timing of events were notably important. 'Now we can have a better understanding of when these events get captured [on ctDNA testing] and what we saw is that mostly these are early events,' said Roschewski, who recently co-authored a review of ctDNA as measurable residual disease in aggressive B-cell lymphoma. Roschewski noted that the benefits of ctDNA are reflected in changes in National Comprehensive Cancer Network (NCCN) Guidelines, which indicate that ctDNA, using a sufficient test — such as PhasED Seq — does appear to be suitable as an alternative to invasive tissue biopsies for positive PET scans. However, the most important thing that the research shows — which validates other findings — is that 'these tests can actually risk-stratify patients who have positive as well as negative PET scans, improving upon our current definition of remission,' Roschewski added. Ultimately, the findings show that 'ultrasensitive ctDNA at the end of frontline therapy for large B-cell lymphoma is the most precise tool to define remission,' he said. Not Ready for Prime Time? However, for all of its promising benefits, a key concern expressed in the Q&A portion of the session was whether ctDNA could indeed be relied upon to replace a tissue biopsy in real-world practice. For instance, while a positive PET scan and positive ctDNA MRD result could likely give clinicians confidence in moving ahead with second-line therapy, the approach may be less clear if a patient is PET-negative but MRD-positive. 'What I worry about is that [ctDNA] is prognostic, but not predictive, and with a relatively small dataset in this study, what are the implications in terms of overtreatment in that kind of situation?' one audience member noted. 'This is an important point,' responded Roschewski. 'However, we should recognize that with the way things are done now, our PET scans have a positive predictive value of about 50%,' he said. 'One of the concerns, and we see it in the data, is that these patients with a positive PET scan are getting second-line therapy when they don't even have any active disease.' 'So, this is something that is already happening,' he explained. Guidelines in such situations suggest either repeating the PET scan or the biopsy, hence delaying therapy. 'So, a negative ctDNA test could help you get information sooner,' Roschewski said. 'But would it improve patient outcomes?' the audience member pressed, getting to the issue of clinical utility. 'That's something we don't have data on yet,' Roschewski conceded. 'I completely agree that this may not be ready for general clinical care without that data, but it may be fine in the context of a clinical trial for now.' Roschewski noted that the good news is that 'at least three clinical trials' are currently being planned to address the issues. He noted that 'we are able to [use this] in other hemolytic malignancies, but we have not gotten there yet [with DLBCL] and we need prospective trials to tell us what to do.' The encouraging news, however, is 'if we see success here, there is no reason to stop at large cell lymphoma. There are other curable lymphomas that we would like to test this in, and I think this could be a domino effect in which we start thinking about this all across therapies for a bunch of different lymphomas,' Roschewski said. ctDNA Benefits in Early Disease Assessment Anticipated Jane N. Winter, MD, professor of medicine, Division of Hematology/Oncology, Northwestern University, Chicago, Illinois, agreed that, with the data showing that ct-DNA is a powerful predictor of clinical outcome and can identify patients at high risk of relapse, 'the big question is how we should use this information.' For instance, 'how important is it to identify refractory disease immediately at the end-of-treatment?' she said in an interview. 'I'm hopeful that ctDNA kinetics early in the course of therapy can help us identify patients for escalation of therapy,' said Winter, a past president of the American Society of Hematology. 'Similarly, we might be able to use ctDNA to deescalate or abbreviate therapy.' Ultimately, the results underscore that 'ctDNA at the end of treatment is a powerful predictor of progression/relapse,' Winter said. 'I'm very interested in using ctDNA as part of an early disease assessment.'
