Blog postings will resume in July 2025

 

Dear Grey Horizon readers, 

Thank you for your continued support of this blog.  Postings will resume in July 2025.  

Vepdegestrant results in longer PFS than fulvestrant in previously treated patients with ESR1-mutated, ER-positive, HER2-negative ABC

 Results from VERITAC-2, an open-label randomized phase III study conducted on "ER-positive HER2- negative advanced breast cancer patients...receiving endocrine therapy plus a CDK4/6 inhibitor" to measure progression-free survival, was reported at the 2025 ASCO Annual Meeting.  Based on findings from VERITAC-2, "vepdegestrant monotherapy showed encouraging clinical activity in patients who had received multiple previous lines of treatment for ER-positive, HER-2 negative ABC." 

To read more about VERITAC-2, click here. 

Sources mentioned: 

• Campone M, De Laurentiis M, Jhaveri K, et al. for the VERITAC-2 Study Group. Vepdegestrant, a PROTAC Estrogen Receptor Degrader, in Advanced Breast Cancer . NEJM; Published online 31 May 2025. DOI: 10.1056/NEJMoa2505725
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• Hamilton EP, De Laurentiis M, Jhaveri K, et al. Vepdegestrant, a PROTAC estrogen receptor (ER) degrader, vs fulvestrant in ER-positive/human epidermal growth factor receptor 2 (HER2)–negative advanced breast cancer: Results of the global, randomized, phase 3 VERITAC-2 study . J Clin Oncol 2025;43(suppl 17):abstr LBA1000. DOI: 10.1200/JCO.2025.43.17_suppl.LBA1000

Supplemental breast cancer imaging techniques could lead to earlier detection of cancer in women with dense breasts

 Results from the Breast Screening - Risk Adapted Imaging for Density (BRAID) study were recently published in The Lancet.  BRAID is "the first randomized controlled trial to compare supplemental imaging of abbreviated magnetic resonance imaging (MRI), automated who breast ultrasound (ABUS), and contrast-enhanced mammography with standard mammography (standard-of-care) in women of average population risk with dense breasts and a negative screening mammogram." 

For a period of 4.5 years (October 2019 - March 2024), 9361 women aged 50-70 across the UK were recruited and randomly assigned to ether abbreviated MRI, ABUS, or contrast-enhanced mammography.   Per 1000 examinations, cancer detection rate was 17.4 for abbreviated MRI, 4.2 for ABUS, and 19.2 for contrast-enhanced mammography. 

Click here to read more about the BRAID trial. 

Sources mentioned: 

• Gilbert FJ, Payne N, Allajbeu I, et al. Comparison of supplemental breast cancer imaging techniques—interim results from the BRAID randomised controlled trial . The Lancet; Published online 21 May 2025. DOI: 10.1016/S0140-6736(25)00582-3
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• Houssami N. Breast cancer screening at a crossroads: supplemental imaging for dense breasts . The Lancet; Published online 21 May 2025. DOI: 10.1016/S0140-6736(25)00803-7

Patient and tumour characteristics may vary across treatment lines in a selected population of patients with mCRC included in randomised trials

 Findings from a large-scale study conducted via the Aide et Recherche en Cancerologie Digestive (ARCAD) database of patients with metastatic colorectal cancer as recently published in the Journal of Clinical Oncology (JCO). According to the study, "almost one in two patients do not receive a subsequent treatment line with second- and third-line treatment rates of 50-60% and 20-30% respectively."  In order to facilitate further research and use, ARCAD is planning to develop Score Prognostic in Oncology Digestive, an app for smartphones, tablets, and computers.  

To learn more about this study click here. 

Source mentioned: 

Bachet J-B, de Gramont A, Raeisi M, et al. Characteristics of Patients and Prognostic Factors Across Treatment Lines in Metastatic Colorectal Cancer: An Analysis From the Aide et Recherche en Cancérologie Digestive Database . JCO; Published online 5 May 2025. DOI: https://doi.org/10.1200/JCO-24-01968

Sun safety declining in Canada amid rise in skin cancer cases

 A recently completed study from McGill University indicates a growing number of Canadians using less sun protection amidst increasing sun exposure time, resulting in rising cases of melanoma.  According to the study, "75% of adult Canadians reported spending at least 30 minutes in the sun...with nearly half staying out for 2 hours or more".  In addition, most of the Canadians polled admitted to irregular or no use of sunscreen, with 33% of those polled experiencing sunburn. 

To learn more about this study, click here. 

Source mentioned: 

Amina Moustaqim-Barrette, Hibo Rijal, Santina Conte, Mahan Maazi, Johnny Hanna, Alexandra Sarah Victoria Kelly, Alicia Belaiche, Alyson McKenna, Sandra Pelaez, François Lagacé, Ivan V Litvinov - Evaluating UV exposure and skin cancer prevention behaviours in Canada: a national population-based cross-sectional study: BMJ Public Health 2025;3:e001983.

InflaMix identifies CAR-T recipients with a preinfusion inflammatory profile indicative of high risk for CAR-T treatment failure

 Findings from the use of InflaMix, a predictive, point-of-care-clinical tool, designed "to identify patients at high risk of treatment failure and support informed risk-benefit discussions.." in patients with non-Hodgkin lymphoma, were recently published in Nature Medicine.  InflaMix, which requires only 1 blood test, "offers an unbiased quantitative assessment of 14 blood markers, 11 of which are routinely assayed for patients with lymphoma."  

To read more about InflaMix, click here. 

Source mentioned: 

Raj SS, Fei T, Fried S, et al. An inflammatory biomarker signature of response to CAR-T cell therapy in non-Hodgkin lymphoma. Nature Medicine; Published online 1 April 2025. DOI: https://doi.org/10.1038/s41591-025-03532-x

Potential for larger gene panels to increase the number of molecularly matched therapies in patients with advanced solid tumours

 Results of ProfiLER-2, a multicentre, prospective study comparing a hospital homemade control gene panel (CTL) to "the commercially available Foundation OneCDX (F1CDX).." was recently published in Nature Medicine.   Of the 741 patients with solid tumours screened in this study, molecular-based recommended therapies were identified with F1CDX in 175 patients and CTL in 125 patients, representing a 14.8% increase when using the F1CDX gene panel.  

To read more about this study, click here. 

Source mentioned: 

Trédan O, Pouessel D, Penel N, et al. Broad versus limited gene panels to guide treatment in patients with advanced solid tumors: a randomized controlled trial. Nature Medicine; Published online 7 April 2025. DOI: https://doi.org/10.1038/s41591-025-03613-x

Cancer mortality prediction for 2025 continues to show favourable trends in the European Union

 A recently completed study of cancer mortality rates across the European Union (EU) over the past 5 years (2020-2025) indicate a lower mortality rate of 3.5% for males and 1.2% in females, with notable decreases in breast cancer for women (9.8% less among those 50-69 years old, and 12.4% less among women 70-79 years old).  The two exceptions to this downward mortality trend were pancreatic cancer for both males and females, and bladder cancer for women.  In addition, despite enhanced tobacco control measures, rate of smoking across the EU was still report at 24%.   

To read more about this study, click here. 

Source mentioned: 

Santucci C, Mignozzi S, Levi F, et al. European cancer mortality predictions for the year 2025 with focus on breast cancer. Annals of Oncology;36(4):460-468.

Adding chemotherapy to radiotherapy not associated with improved OS for patients with intermediate-risk cervical cancer

 A population-based cohort study recently published in JAMA Oncology found "no significant overall survival benefit from the addition of concomitant chemotherapy to radiotherapy in patients with intermediate-risk cervical cancer." While hysterectomy and surgical lymph node assessment is considered standard treatment for early-stage cervical cancer, nearly 60% of patients continue receiving chemoradiotherapy for intermediate-risk cases "despite the absence of clear benefit." 

To read more about this study, click here: 

Source mentioned: 

Agustí N, Viveros-Carreño D, Wu C-F, et al. Adjuvant Chemoradiotherapy vs Radiotherapy Alone for Patients With Intermediate-Risk Cervical Cancer. JAMA Oncology; Published online 13 March 2025. doi:10.1001/jamaoncol.2025.0146

Suggesting a deadline in the invitation letter to FIT colorectal cancer screening results in more timely FIT return

 Results from the timeframe and planning tool (TEMPO) study, part of the Scottish Bowel Screening Program, has determined that "including a deadline of 2 weeks for faecal immunochemical test (FIT) return in the invitation letter resulted in more rapid FIT returns, fewer reminder letters send, and marginally higher return rates..."  The authors of the TEMPO study also stated that establishing FIT return deadlines is more cost-effective and increases compliance with screening behaviour, as current FIT uptake in Scotland is 66% compared to an average of 50% across other European countries.  

To learn more about the TEMPO study, click here. 

Sources: 

• Robb KA, Young B, Murphy MK, et al. Behavioural interventions to increase uptake of FIT colorectal screening in Scotland (TEMPO): a nationwide, eight-arm, factorial, randomised controlled trial. The Lancet; Published online 12 March 2025. DOI: https://doi.org/10.1016/S0140-6736(24)02813-7
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• Brenner H, Hoffmeister M. Cost-effective improvement of real-world cancer screening. The Lancet; Published online 12 March 2025. DOI: https://doi.org/10.1016/S0140-6736(25)00108-4

Real-world patients with cancer show lower survival times and treatment-associated survival benefits compared to those included in RCTs

 Findings from TrialTranslator, a machine-learning model involving randomized clinical trials (RCTs), indicates that "median overall survival treatment benefit for real-word patients...[is] on average, 3 months lower than in RCTs..."  While the authors of this TrialTranslator study conclude that "prognostic heterogeneity among real-world patients with cancer plays a substantial role in the limited generalizability of RCT results", machine learning frameworks have been shown to be of benefit in guiding trial design and planning future enhancements in cancer care. 

To read more about TrialTranslator, click here. 

Source mentioned: 

Orcutt X, Chen K, Mamtani R, et al. Evaluating generalizability of oncology trial results to real-world patients using machine learning-based trial emulations. Nature Medicine; Published online 3 January 2025.

Distinct patient, tumour, treatment characteristics and a different pattern and risk of survival events over time between young BRCA1/2 carriers

 Findings from a large-scale 20-year multicentre hospital=based retrospective cohort study were recently published in Journal of Clinical Oncology.  Conducted on 4752 patients with BRCA1 or BRCA2, "diagnosed with stage I-III invasive breast cancer at 40 years or younger...provides evidence on the different clinical behaviour of breast cancer according to the specific BRCA gene and the association of the timing of genetic testing with prognosis." This study also emphasized the importance of early identification of women carrying a BRCA1 or BRCA2 variant, in addition to providing genetic counselling and creating greater awareness about "early detection options that may lead to better prognosis." 

Source mentioned:  

Lambertini M, Blondeaux E, Tomasello LM, et al. Clinical Behavior of Breast Cancer in Young BRCA Carriers and Prediagnostic Awareness of Germline BRCA Status. JCO; Published online 24 February 2025. DOI: https://doi.org/10.1200/JCO-24-01334

Clinical benefit of pembrolizumab in patients with previously treated advanced clear cell gynaecological cancers

 Results from the United Kingdom-led PEACOCC phase II trial regarding the benefits of pembrolizumab on clear cell gynecological cancers was recently published in JAMA Oncology.   According to the study authors, "less than 5% of clear cell gynaecological cancers" are attributed to the vagina, vulva, and cervix. While this clear-cell histological subtype is rare, the authors are adamant that "tissue collection including contemporaneous trial biopsies allows further translational study of the molecular and immune landscape."   

To learn more about the PEACOCC trial, click here.  

Source mentioned: 

Kristeleit R, Devlin M-J, Clamp A, et al. Pembrolizumab in Patients With Advanced Clear Cell Gynecological Cancer A Phase 2 Nonrandomized Clinical Trial. JAMA Oncology; Published online 6 February 2025. doi:10.1001/jamaoncol.2024.6797

Less frequent mammographic surveillance non-inferior compared with annual mammograms after diagnosis of breast cancer in women aged 50 years or older

 Results of Mammo-50, a randomized phase III trial conducted across the United Kingdom on women aged 50 or older was recently published in The Lancet.  Findings from Mammo-50 indicate that women 50 years or older when diagnosed with breast cancer "who have undergone annual mammographic surveillance for 3 years post diagnosis...[and who] show no signs of recurrence, can safely have less frequent mammograms."  The authors further state that this evidence may result in changes to guidelines, both within the U.K. and globally as well. 

To learn more about the Mammo-50 trial, click here. 

Sources mentioned: 

• Dunn JA, Donnelly P, Elbeltagi N, et al. Annual versus less frequent mammographic surveillance in people with breast cancer aged 50 years and older in the UK (Mammo-50): a multicentre, randomised, phase 3, non-inferiority trial. The Lancet 2025;405(10476):396–407.
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• Mann RM. Rethinking surveillance after breast cancer. The Lancet 2025;405(10476):356-358.

Cancer prevention and screening account for most cancer deaths averted among different interventions across the cancer control continuum

 An extensive study of population-level mortality data, along with cancer prevention and screening interventions across common cancer in the United States over the past 45 years was recently compiled by the National Cancer Institute.  According to the authors, "an estimated 5.94 million cancer deaths were averted for breast, cervical, colorectal, lung, and prostate cancers combined, [where] cancer prevention and screening efforts averted 8 of 10 (4.75 million) deaths." The authors further emphasize the importance of early diagnosis and prevention may "reduce or eliminate treatment, minimize harmful adverse effects of cancer or treatment, and reduce the financial burden of cancer." 

To read more about this study, click here. 

Source mentioned: 

Goddard KAB, Feuer EJ, Mandelblatt JS, et al. Estimation of Cancer Deaths Averted From Prevention, Screening, and Treatment Efforts, 1975-2020. JAMA Oncology; Published online 5 December 2024. doi: 10.1001/jamaoncol.2024.5381

Chemotherapy-free regimen of tucatinib and trastuzumab shows anti-tumour activity with durable responses in patients with HER2-mutated metastatic breast cancer

 Results of the open-label phase II trial, SGNTUC-019, "evaluating tucatinib in combination with trastuzumab" in patients with HER2-mutated metastatic breast cancer, showed that this form of treatment was well tolerated with diarrhea noted as the most common adverse event.  In addition, study authors noted that most events had a grade 1 severity, which were managed with standard clinical care; grade 3 occurrence was noted in 13% of cases.  

To learn more about this study, click here. 

Source mentioned: 

Okines AFC, Curigliano G, Mizuno N, et al. Tucatinib and trastuzumab in HER2-mutated metastatic breast cancer: a phase 2 basket trial. Nature Medicine; Published online 17 January 2025. DOI: https://doi.org/10.1038/s41591-024-03462-0

Active monitoring promising for women with low-risk ductal carcinoma in situ

Results of the intention-to-treat analysis from the COMET study, "a prospective randomized, pragmatic non-inferiority trial..." for women with low-risk ductal carcinoma in situ (DCIS) was recently presented at the San Antonio Breast Cancer Symposium.  Conducted on 995 women 40 years or older with a new diagnosis of hormone receptor-positive grade 1 or grade 2 DCIS without invasive cancer, the COMET study supports the notion that a "standard management strategy for low-risk DCIS requires longer follow-up for most patients."   

To learn more about the COMET study, click here. 

Sources mentioned: 

• Hwang ES, Hyslop T, Lynch T, et al. for the COMET Study Investigators. Active Monitoring With or Without Endocrine Therapy for Low-Risk Ductal Carcinoma In Situ The COMET Randomized Clinical Trial. JAMA; Published online 12 December 2024. doi: 10.1001/jama.2024.26698
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• Morrow M, Barrio AV. Is It Time to Abandon Surgery for Low-Risk DCIS? JAMA; Published online 12 December 2024. doi:10.1001/jama.2024.26723