Bekaii-Saab TS, Melisi D, Wilmink H
… +24 more, Garufi C, Tran N, Tortora G, De Braud F, Frodin JE, Lonardi S, Lin E, Babiker H, Lin B, Fornaro L, Muñoz Martín A, Bridgewater J, Knox JJ, De Vos-Geelen J, Scott-Brown M, Veronese L, Ioannidis S, Gilmartin A, Janik JE, Guo Y, Furuse J, Ioka T, Rimassa L, Vogel A
PURPOSE: Cholangiocarcinoma is a rare cancer associated with poor prognosis. Pemigatinib was the first FGFR1-3 inhibitor approved for second-line therapy and beyond, on the basis of the phase II FIGHT-202 trial. Here, we...PURPOSE: Cholangiocarcinoma is a rare cancer associated with poor prognosis. Pemigatinib was the first FGFR1-3 inhibitor approved for second-line therapy and beyond, on the basis of the phase II FIGHT-202 trial. Here, we assess efficacy and safety of first-line pemigatinib. METHODS: FIGHT-302 is a phase III, randomized, global trial evaluating pemigatinib as first-line therapy (ClinicalTrials.gov identifier: NCT03656536). Adults with advanced cholangiocarcinoma with rearrangement were randomized 1:1 to receive pemigatinib (13.5 mg once daily) or chemotherapy (1,000 mg/m gemcitabine plus 25 mg/m cisplatin once per day on days 1 and 8 of every 3-week cycle for ≤8 cycles) and were stratified by prior receipt of chemotherapy, geographic region, and tumor burden. Pemigatinib crossover was allowed for patients progressing on chemotherapy. The primary end point was progression-free survival (PFS). Secondary efficacy, safety, and exploratory end points were also analyzed. RESULTS: Overall, 4,563 patients were prescreened, 196 were screened, and 167 randomly assigned to receive pemigatinib (n = 83) or chemotherapy (n = 84) before early closure of the study because of a change in standard of care. The median PFS was 8.3 months in the pemigatinib group versus 6.8 months in the chemotherapy group (hazard ratio, 0.58 [95% CI, 0.39 to 0.87]; nominal = .0078); objective response rate was 47% versus 15%, and the median duration of response was 14.2 versus 6.3 months. Median overall survival was similar (24.4 25.0 months, respectively). In the crossover group (n = 42, second-line pemigatinib), the median PFS was 8.1 months. Safety was consistent with the known profile of pemigatinib. CONCLUSION: To our knowledge, this was the largest, first-line, randomized, phase III trial of a targeted therapy for advanced rearranged cholangiocarcinoma. Pemigatinib demonstrated prolonged median PFS compared with chemotherapy, with no new safety findings.
Khattak A, Carlino MS, Meniawy T
… +18 more, Ansstas G, Taylor MH, Kim KB, McKean M, Long GV, Sullivan RJ, Faries M, Tran TT, Cowey CL, Pecora A, Medina T, Atkinson V, Krepler C, Jemielita T, Mao H, Chow J, Ojalvo LS, Mehnert JM
Intismeran autogene (intismeran; formerly V940 or mRNA-4157) is an mRNA-based individualized neoantigen therapy. We report 5-year outcomes of intismeran plus pembrolizumab from the phase 2b KEYNOTE-942 study (NCT03897881...Intismeran autogene (intismeran; formerly V940 or mRNA-4157) is an mRNA-based individualized neoantigen therapy. We report 5-year outcomes of intismeran plus pembrolizumab from the phase 2b KEYNOTE-942 study (NCT03897881). Eligible patients with resected stage IIIB‒IV cutaneous melanoma were randomized 2:1 to receive 9 doses of intramuscular intismeran 1 mg Q3W plus 18 doses of intravenous pembrolizumab 200 mg Q3W or 18 doses of intravenous pembrolizumab 200 mg Q3W. Primary endpoint was recurrence-free survival (RFS); secondary endpoints included distant metastasis-free survival (DMFS) and safety. Five-year analyses were descriptive. Among 157 randomized patients (intismeran plus pembrolizumab, n=107; pembrolizumab, n=50), median planned follow-up at data cutoff (December 15, 2025) was 60.3 (range, 50.5‒76.4) months. Intismeran plus pembrolizumab continued to prolong RFS (HR, 0.510; 95% CI, 0.294‒0.887) and DMFS (0.411; 0.200‒0.843), with a favorable trend in overall survival (0.471; 0.165‒1.345) versus pembrolizumab. Safety profile continued to be manageable, with no new safety signals. Intismeran plus pembrolizumab was associated with increased T-cell receptor clonality and novel clonotypes versus pembrolizumab; greater novel clone expansion was observed in patients without versus with recurrence in the combination arm. After 5 years' follow-up, intismeran plus pembrolizumab demonstrated sustained, durable treatment benefits versus pembrolizumab alone in resected high-risk melanoma.
Nakayama I, Ryu MH, Lim SH
… +19 more, Kim JG, Omori T, Oh SC, Kim JY, Rha SY, Lee KW, Machida N, Sym SJ, Narita Y, Park YI, Hara H, Hosaka H, Kang B, Kim IH, Bai LY, Hirashima Y, Hagihara S, Yamamoto T, Shitara K
PURPOSE: EP4, a key receptor in the PGE axis, mediates tumor immunosuppression; the EP4 antagonist ONO-4578 plus nivolumab showed manageable safety, immune activation, and preliminary antitumor activity in previously tre...PURPOSE: EP4, a key receptor in the PGE axis, mediates tumor immunosuppression; the EP4 antagonist ONO-4578 plus nivolumab showed manageable safety, immune activation, and preliminary antitumor activity in previously treated gastric/gastroesophageal junction cancer (G/GEJC). This study explored whether ONO-4578 enhances the efficacy of nivolumab plus chemotherapy in unresectable advanced or recurrent G/GEJC. PATIENTS AND METHODS: This multicenter, double-blind, randomized phase 2 study enrolled chemotherapy-naïve patients with HER2-negative unresectable advanced or recurrent G/GEJC. Patients were randomized (2:1) to receive oral ONO-4578 or matching placebo, each in combination with nivolumab and oxaliplatin-based chemotherapy. The primary endpoint was investigator-assessed progression-free survival (PFS). Secondary endpoints included overall survival (OS), objective response rate (ORR), and safety. RESULTS: At the data cutoff, 226 patients were randomized to the ONO-4578 group (n = 150) and the placebo group (n = 76). Adding ONO-4578 significantly improved PFS (hazard ratio of 0.67; 90% confidence interval, 0.48-0.92; p-value, 0.040 [prespecified two-sided α = 0.10]), with favorable OS at a prespecified analysis with limited follow-up (hazard ratio of 0.60; 95% confidence interval, 0.37-0.96) and ORR (62.0% vs 48.7%). Exploratory subgroup analyses suggested that ONO-4578 regimen provided greater benefit in PD-L1 CPS ≥1, whereas no clear benefit in CPS <1/indeterminate patients. In an extended follow-up exploratory OS analysis with a minimum follow-up of 16.1 months, OS numerically favored ONO-4578 regimen. Common treatment-emergent adverse events in the ONO-4578 group were diarrhoea (55.7% vs 45.3%), and anaemia (55.0% vs 34.7%). CONCLUSION: This study demonstrated promising efficacy and acceptable safety of an ONO-4578 regimen as first-line treatment for HER2-negative unresectable advanced or recurrent G/GEJC. These findings warrant confirmation in a phase 3 trial.
Burtness B, Rosenberg AJ, Calderon B
… +31 more, Lim SM, Yang MH, Li SH, Kadowaki S, Swiecicki PL, Geiger JL, Ince W, Hahn D, Guo Y, Adkins D, Metcalf R, Ahn MJ, Sukari A, Braña I, Keam B, Tanaka H, Sheth S, Oliva M, Lyu X, Curtin JC, Toyoizumi K, Xie J, Wade M, Diorio B, Kapoor A, Yilmaz E, Baig M, Kim P, Verheijen RB, Shah S, Harrington KJ
Single-agent paclitaxel or cetuximab after immune checkpoint inhibitor (ICI) and chemotherapy demonstrated objective response rates (ORRs) of 21%-24% in recurrent/metastatic (R/M) head/neck squamous cell cancer (HNSCC)....Single-agent paclitaxel or cetuximab after immune checkpoint inhibitor (ICI) and chemotherapy demonstrated objective response rates (ORRs) of 21%-24% in recurrent/metastatic (R/M) head/neck squamous cell cancer (HNSCC). EGFR and MET are overexpressed in R/M HNSCC. Amivantamab, an EGFR-MET bispecific antibody, may be a rational treatment. Cohort 1 of OrigAMI-4 (NCT06385080) evaluated subcutaneous amivantamab administered every three weeks in participants with R/M HNSCC after PD-(L)1 inhibitor and platinum-based chemotherapy. Prior anti-EGFR was exclusionary. The primary endpoint was RECIST v1.1 ORR. Secondary endpoints included duration of response (DoR), progression-free survival (PFS), overall survival (OS), and safety. In 102 participants, blinded independent central review-assessed ORR was 42% (95% CI, 32-52); the complete response rate was 15%. Median DoR was not reached (NR; 95% CI, 6.9-NR); 56% of responses lasted ≥6 months. Investigator-assessed ORR was 47% (95% CI, 37-57). At a median follow-up of 11.8 months (range, 1.1-21.9), median PFS and OS were 6.8 months (95% CI, 5.2-8.3) and 12.5 months (95% CI, 10.2-16.8), respectively. Adverse events were consistent with previous experience with no new safety signals. Treatment-related discontinuations were low (8%). Amivantamab demonstrated greater antitumor activity in participants previously exposed to ICI and chemotherapy than what has been reported for paclitaxel or cetuximab.
Necchi A, de Jong JJ, Maiorano BA
… +20 more, Proudfoot JA, Basile G, Cigliola A, Mercinelli C, Tateo V, Piacentini M, Crupi E, Pastorino GL, Latini G, Tomasi E, Davicioni E, Moschini M, Brembilla G, Colecchia M, de Cobelli F, Ross JS, Madison R, Tambaoan CFB, Briganti A, Montorsi F
PURPOSE: To evaluate neoadjuvant sacituzumab govitecan (SG), followed by radical cystectomy (RC), in patients with muscle-invasive bladder cancer (MIBC) who are ineligible for/refuse neoadjuvant chemotherapy (NAC). We re...PURPOSE: To evaluate neoadjuvant sacituzumab govitecan (SG), followed by radical cystectomy (RC), in patients with muscle-invasive bladder cancer (MIBC) who are ineligible for/refuse neoadjuvant chemotherapy (NAC). We report the results of the primary analysis and biomarker analyses of the phase II SURE-01 trial (ClinicalTrials.gov identifier: NCT05226117). PATIENTS AND METHODS: Patients were age 18 years and older, had Eastern Cooperative Oncology Group performance status 0-1, had histologically confirmed cT2-T4aN0M0 MIBC, were ineligible/refusing NAC, and were scheduled for RC received four cycles of SG 10 mg/kg on day 1 and day 8, once every 3 weeks, followed by RC. The primary outcome measure was the pathologic complete response (pT0N0) rate. Transcriptome-wide analyses and comprehensive genomic profiling assays were performed on baseline tumor samples. RESULTS: From March 2022 to July 2025, 44 patients were treated and efficacy evaluable. After the initial eight patients enrolled, the protocol was amended with a SG dose of 7.5 mg/kg, with primary prophylaxis for neutropenia, due to the occurrence of two deaths (one treatment-related). Subsequent grade 3-4 treatment-related adverse-events occurred in 5 patients (13.9%). Twenty-six patients (59.1%) had a cT3-4 stage and 20 (45.5%) had a variant histology. Fourteen patients (31.8%) refused to undergo RC, accounting for 12 repeating a transurethral resection of the bladder tumor and two undergoing active surveillance. The median follow-up was 22 months (IQR, 15-26). In the intention-to-treat population, although the protocol-defined ypT0N0 rate was 9.1% (95% CI, 2.5 to 21.7), the overall ypT0N0-x rate was 29.5% (95% CI, 16.7 to 45.2), with an enrichment of ypT0 responses in nonluminal subtypes (46% 14% of luminal). The 24-month event-free survival (EFS) rate was 71.4% (95% CI, 58 to 87.8), with longer EFS for participants with lower TOP1-expressing tumors. CONCLUSION: Neoadjuvant SG, at the reduced dose of 7.5 mg/kg, was active with a manageable safety profile, corroborating TROP2 as a suitable target for MIBC.
Gandini S, Guerrieri-Gonzaga A, Serrano D
… +20 more, Rizzo R, Lazzeroni M, Puntoni M, Buttiron Webber T, Aurilio G, Johansson H, Carbone A, Giordano L, Digennaro M, Cortesi L, Millo F, Cagossi K, Aprile G, Serra P, Gallerani E, Debiasi M, Sousa B, Gouveia P, Bonanni B, DeCensi A
PURPOSE: Tamoxifen 20 mg once-daily reduces the risk of breast cancer recurrence after ductal carcinoma in situ (DCIS), but its use is limited by adverse effects. Lower doses may be effective, but benefit durability and...PURPOSE: Tamoxifen 20 mg once-daily reduces the risk of breast cancer recurrence after ductal carcinoma in situ (DCIS), but its use is limited by adverse effects. Lower doses may be effective, but benefit durability and differences according to menopausal status and site of recurrence remain uncertain. METHODS: We conducted an individual-participant pooled analysis of three clinical studies involving women with estrogen receptor-positive or unknown DCIS, microinvasive carcinoma, or high-risk breast lesions. Participants received low-dose tamoxifen (5 mg once daily or 10 mg once-every other day for 2-5 years) or a control intervention. The primary end point was breast cancer-free interval, defined as the first occurrence of any ipsilateral or contralateral invasive breast cancer, DCIS, regional recurrence, or distant recurrence. Hazard ratios (HRs) were estimated with mixed-effects Cox models accounting for between-study variability. RESULTS: Among 1,545 women included with a median follow-up of 9.4 years, low-dose tamoxifen reduced breast cancer events overall, with evidence of treatment heterogeneity according to menopausal status ( = .01). In postmenopausal women, breast cancer events occurred in 40 of 335 receiving low-dose tamoxifen versus 93 of 401 controls (HR, 0.51 [95% CI, 0.35 to 0.73]), with a 10-year absolute reduction of 11.2%. Among premenopausal women, no significant reduction was observed (HR, 0.90 [95% CI, 0.70 to 1.17]), although contralateral breast cancer was reduced (HR, 0.45 [95% CI, 0.26 to 0.76]). Serious adverse events were infrequent and similar between groups. CONCLUSION: Low-dose tamoxifen was associated with a sustained reduction in breast cancer events, with differences by menopausal status and site of event. These findings support endocrine dose de-escalation to improve the benefit-risk profile of preventive therapy in DCIS and high-risk lesions.
PURPOSE: The phase III CHALLENGE trial (CCTG CO.21) demonstrated that a 3-year structured exercise program (SEP) improved disease-free and overall survival versus health education materials (HEM) in patients with stage I...PURPOSE: The phase III CHALLENGE trial (CCTG CO.21) demonstrated that a 3-year structured exercise program (SEP) improved disease-free and overall survival versus health education materials (HEM) in patients with stage III or high-risk stage II colon cancer after surgery and adjuvant chemotherapy. We assessed the cost-effectiveness of the SEP versus HEM. METHODS: This prespecified economic evaluation used prospectively collected data from all trial participants (N = 889). The base case adopted the Canadian public payer perspective and included direct health care costs over a 5-year time horizon with a 1.5% discount rate. 36-Item Short Form (SF-36) outcomes were mapped to Short-Form 6-Dimension (SF-6D) utilities using a validated algorithm. Mean costs (2024 in Canadian dollars [CAD]) and effects (life-years [LYs] and quality-adjusted LYs [QALYs]) per participant in each intervention group were used to estimate the incremental costs, incremental LYs/QALYs, incremental cost-effectiveness ratio (ICER, $ CAD/life-year gain [LYG]), and incremental cost-utility ratio ($ CAD/QALY) when applicable. Uncertainty was assessed via bootstrapping (1,000 samples). Notable scenario analyses included a 10-year time horizon and a societal perspective incorporating lost wages because of missed work, measured through the Work Productivity and Activity Impairment questionnaire. RESULTS: In the base case, despite an up-front cost of $2,917 (CAD)/participant to provide the SEP, the SEP strategy (total cost: $31,957 (CAD)/participant) was dominant over HEM (total cost: $33,546 (CAD)/participant), being less costly (-$1,589/participant) and more effective (+0.05 LYs/participant; +0.10 QALYs/participant). The SEP was dominant in 53% of bootstrap samples, and 80% fell below a $50,000 (CAD) per QALY willingness-to-pay threshold. Major cost drivers were cancer recurrence or new malignancy and anticancer therapy. Scenario analyses were consistent with the base case. CONCLUSION: The SEP was less costly and more effective than HEM. This study can inform payers and health systems with implementation of SEPs in routine care.
PURPOSE: In immunoglobulin light chain (AL) amyloidosis, amyloid fibrils cause organ dysfunction. Anselamimab, a monoclonal antibody, selectively binds to amyloid fibrils, accelerating their clearance. METHODS: Newly dia...PURPOSE: In immunoglobulin light chain (AL) amyloidosis, amyloid fibrils cause organ dysfunction. Anselamimab, a monoclonal antibody, selectively binds to amyloid fibrils, accelerating their clearance. METHODS: Newly diagnosed patients with European modification of Mayo 2004 stage IIIa or IIIb AL amyloidosis were randomly assigned to receive anselamimab or placebo with cyclophosphamide, bortezomib, and dexamethasone (with or without daratumumab). The primary end point was a hierarchical composite of time to all-cause mortality (ACM) and frequency of cardiovascular hospitalizations (CVHs), analyzed using the Finkelstein-Schoenfeld test and win ratio estimation. RESULTS: Among 406 randomly assigned patients, the primary end point win ratio for anselamimab versus placebo was 1.11 (95% CI, 0.83, 1.50; = .332) and the hazard ratio (HR) for ACM was 0.80 (95% CI, 0.57, 1.13; = .290). CVH rates in the anselamimab and placebo groups were 0.59 (95% CI, 0.42, 0.83) and 0.89 (95% CI, 0.55, 1.43), respectively ( = .145). Among patients with kappa isotype (n = 72), the win ratio was 2.06 (95% CI, 0.98, 4.31; = .100) and anselamimab reduced ACM by 62% versus placebo (HR, 0.38; 95% CI, 0.17 to 0.86; nominal = .012), and CVH by 71% (IRR, 0.29; 95% CI, 0.10 to 0.87; nominal = .028) with improvements in Kansas City Cardiomyopathy Questionnaire-Overall Score. There was no clinical benefit observed in the lambda population. Anselamimab was generally well-tolerated; safety data were comparable between treatment arms overall. CONCLUSION: Treatment with anselamimab, an antifibril antibody used alongside antiplasma cell dyscrasia therapy, while not meeting the primary end point in the overall population, significantly improved ACM and CVH in patients with kappa AL, potentially offering a new therapeutic option for this isotype.
Cathomas R, Petrausch U, Hayoz S
… +22 more, Spahn M, Bubendorf L, Schäuble K, Strebel RT, Niederberger P, Stenner F, Hirschi A, Vogl U, Lorch A, Tsantoulis P, Aeppli S, Erdmann A, Fischer Maranta A, Fankhauser C, Hötker AM, Pausch AM, Herzig P, Le Gall V, Zippelius A, Chiquet S, Rothschild SI, Rentsch CA
PURPOSE: Intravesical Bacillus Calmette-Guérin (BCG) is highly effective in non-muscle-invasive bladder cancer (MIBC) but has not been evaluated in MIBC. The recombinant BCG vaccine VPM1002BC (rBCG) has potentially enhan...PURPOSE: Intravesical Bacillus Calmette-Guérin (BCG) is highly effective in non-muscle-invasive bladder cancer (MIBC) but has not been evaluated in MIBC. The recombinant BCG vaccine VPM1002BC (rBCG) has potentially enhanced immunogenicity and an improved safety profile. We investigated neoadjuvant intravesical rBCG combined with chemoimmunotherapy in MIBC. PATIENTS AND METHODS: SAKK 06/19 was an open-label single-arm phase II trial for cT2-T4a N0-1 MIBC eligible for cisplatin and radical cystectomy with lymph node dissection (RC-LND). rBCG was instilled once per week three times starting on day 1. Atezolizumab was administered on day 1 for a total of four doses, and cisplatin/gemcitabine was started on day 22 for four cycles followed by RC-LND. Adjuvant atezolizumab was only administered in the case of >yT1 ypN0. The primary end point was centrally reviewed pathologic complete response (pCR, ypT0 ypN0). Based on Simon's minimax two-stage design with H0 pCR ≤35%, H1 pCR ≥55%, one-sided alpha 5%, and power 80%, 46 patients were needed. Secondary end points included pathologic overall response (PaR, ≤ypT1 ypN0), event-free survival (EFS), overall survival (OS), and safety. RESULTS: Forty-seven patients were included between April 2022 and April 2025. Seven patients did not undergo RC-LND (six declined, one unfit for surgery). rBCG was instilled in 95%, and 78% had all three doses. Centrally reviewed pCR was 68% (27 of 40; one-sided 95% CI lower boundary 53%), and PaR was 83% (33 of 40; 95% CI, 67 to 93). Treatment-related adverse events (any grade, grade 3, grade 4) were 42%, 9%, and 0% for rBCG; 55%, 15%, and 2% for atezolizumab; and 96%, 38%, and 17% for chemotherapy. CONCLUSION: To our knowledge, this is the first trial combining intravesical rBCG with chemoimmunotherapy in MIBC, demonstrating high pCR and PaR rates that warrant further investigation in prospective randomized trials.
Kotecha R, Polley MY, Vogelbaum MA
… +23 more, Perry A, Ashby L, Modi JM, Alleman AM, Tsien CI, Barani IJ, Li J, Braunstein S, Whitton AC, Bovi JA, Deb N, Lindhorst SM, Shrieve DC, Robinson CG, Shu HG, Vempati P, Mishra MV, Suh JH, Bloom B, Hunter GK, Won M, Mehta MP, Rogers CL
J Clin Oncol
· 2026 May · PMID 42202246
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NRG Oncology RTOG 0539 was a prospective phase II trial of risk-adapted radiotherapy for patients with WHO grade 1-3 meningioma. Low-risk (group 1, n = 60) was defined as a grade 1 tumor after gross total resection or su...NRG Oncology RTOG 0539 was a prospective phase II trial of risk-adapted radiotherapy for patients with WHO grade 1-3 meningioma. Low-risk (group 1, n = 60) was defined as a grade 1 tumor after gross total resection or subtotal resection (GTR/STR) and prospectively monitored. Intermediate-risk (group 2, n = 52) was defined as recurrent grade 1 or newly diagnosed grade 2 tumor after GTR and treated with radiotherapy (54 Gy). High-risk (group 3, n = 53) included a newly diagnosed grade 2 tumor after STR, newly diagnosed grade 3 tumor, or recurrent grade 2 or 3 tumor and treated with radiotherapy (60 Gy). Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method. The median follow-up times for the low-, intermediate-, and high-risk cohorts were 12.1, 12.0, and 11.1 years, respectively. The 10-year PFS and OS rates for the low-, intermediate-, and high-risk cohorts were 85.2% and 94.1%, 72.2% and 84.7%, and 42.5% and 51.1%, respectively. Five patients (9.6%) and eight patients (15.1%) had a grade 3+ toxicity attributed to radiotherapy in the intermediate- and high-risk cohorts, respectively. The long-term outcomes using this risk-adapted approach support observation for low-risk patients, inform radiotherapy patient selection and practice standards for intermediate- and high-risk patients, and provide comparative benchmarks for future trials.
PURPOSE: We evaluated the reach, treatment selection, and effectiveness of a population-based, opt-out smoking cessation outreach program, No Smoker Left Behind, implemented in a socioeconomically and racially diverse ca...PURPOSE: We evaluated the reach, treatment selection, and effectiveness of a population-based, opt-out smoking cessation outreach program, No Smoker Left Behind, implemented in a socioeconomically and racially diverse cancer patient population. METHODS: Patients seeking oncology care at the University of Chicago Comprehensive Cancer Center between 2019 and 2024 were screened for smoking status as documented in the electronic health record. Adults age 18 years and older categorized as currently smoking (past month) were systematically contacted via interactive voice response phone calls, texts, and emails for up to 6 months. They were offered several cessation treatment options, including medication and counseling referrals (ie, group program, quitline, and text message program). Program involvement and cessation outcomes were compared by cancer type (ie, smoking- or non-smoking-related) and race. A cost-outcome analysis was also conducted. RESULTS: Of 37,478 patients with cancer, 3,706 (9.9%) were deemed eligible and contacted, of whom 57.0% were male, 46.6% Black, and 63.8% publicly insured. Of those selecting cessation treatments (n = 1,089), most self-selected both medication and counseling (70.6%), with 873 receiving referrals or connection to cessation support. Among patients who completed day 180 follow-up (37.5% of those receiving referrals), 16.2% (53/327) self-reported ≥8-day abstinence. Patients with smoking-related cancers had higher abstinence rates than patients with non-smoking-related cancers (23.7% 14.7%). Black patients had higher program involvement and treatment referral rates, but significantly lower smoking abstinence compared with White patients (14.4% 25.7%). Costs-per-patient referred to treatment were $415 US dollars (USD) and costs-per-quit were $6,067 USD. CONCLUSION: Population-based, proactive opt-out outreach programs provide a feasible approach for offering multiple cessation treatment options that allow for patient preference and customization to optimize treatment accessibility. As health care systems expand access to tobacco cessation as part of cancer care, implementing resource-efficient models will become increasingly important.
Thibault C, Bennamoun M, Fléchon A
… +19 more, Gravis G, Pouessel D, Combe P, Borchiellini D, Loriot Y, Laguerre B, Barthélémy P, Huillard O, Gross-Goupil M, Le Roy A, Jaffrelot L, Cancel M, Audenet F, Belhouari H, Kaci G, Lepicard E, Vernerey D, Henriques J, Oudard S
PURPOSE: To evaluate the efficacy and safety of neoadjuvant dose-dense methotrexate, vinblastine, doxorubicin, and cisplatin (ddMVAC) combined with durvalumab ± tremelimumab in patients with muscle-invasive bladder cance...PURPOSE: To evaluate the efficacy and safety of neoadjuvant dose-dense methotrexate, vinblastine, doxorubicin, and cisplatin (ddMVAC) combined with durvalumab ± tremelimumab in patients with muscle-invasive bladder cancer (MIBC). METHODS: NEMIO (ClinicalTrials.gov identifier: NCT03549715) is a multicenter, randomized, noncomparative phase II trial in cT2-T4a N0-1 cisplatin-eligible MIBC planned for radical cystectomy (RC). Patients received ddMVAC (cisplatin 70 mg/m, methotrexate 30 mg/m, doxorubicin 30 mg/m, and vinblastine 3 mg/m on days 1, and pegfilgrastim 6 mg on days 2) once every 2 weeks × four cycles plus durvalumab ± tremelimumab (durvalumab 1,500 mg and tremelimumab 75 mg) once every 4 weeks × two doses (C1D1 and C3D1) before RC. Coprimary end points (local assessment) were pathologic complete response (pCR; ypT0N0) and grade ≥3 treatment-related adverse events (TRAEs). The study was considered positive if the pCR rate was ≥45% and the rate of grade ≥3 TRAEs was ≤30%. RESULTS: From 2018 to 2022, 119 patients received ddMVAC + durvalumab (n = 60) or ddMVAC + durvalumab + tremelimumab (n = 59); 113 underwent RC. The overall Bayesian posterior mean pCR rate was 48.70% (95% CI, 35.93 to 61.56) with doublet and 46.27% (95% CI, 33.92 to 58.85) with triplet. Among 103 patients with PD-L1 data (exploratory), Bayesian posterior mean pCR was 68.25% (95% CI, 54.57 to 80.49) in PD-L1-high tumors versus 33.49% (95% CI, 22.13 to 45.91) in PD-L1-low/negative tumors. Bayesian posterior mean grade ≥3 TRAEs occurred in 40.95% (95% CI, 32.50 to 49.69) overall (30.48% [95% CI, 20.00 to 42.08] doublet; 49.63% [95% CI, 37.55 to 61.73] triplet); immune-related adverse events occurred in 26.9% (grade ≥3 4.2%). Two-year event-free survival and overall survival rates were 75% and 85% in the doublet arm, and 77% and 88% in the triplet arm, respectively. CONCLUSION: Neoadjuvant ddMVAC plus durvalumab demonstrated encouraging pCR rates, favorable early survival outcomes, and manageable safety profile. Adding tremelimumab provides similar pCR but worse toxicity. These results support further study of ddMVAC plus durvalumab as a neoadjuvant chemoimmunotherapy strategy for localized MIBC, to be evaluated in comparative trials within an evolving perioperative treatment landscape.
This piece looks at the challenges of day-to-day clinical practice in oncology through the lens of speculative fiction and how we struggle, as physicians and as patients, to tell the difference between what we know and w...This piece looks at the challenges of day-to-day clinical practice in oncology through the lens of speculative fiction and how we struggle, as physicians and as patients, to tell the difference between what we know and what we can only hope for.
PURPOSE: Integrating external control data into clinical trial designs and analyses has the potential to accelerate drug development processes. We reanalyzed the three experimental arms of the Individual Screening Trial...PURPOSE: Integrating external control data into clinical trial designs and analyses has the potential to accelerate drug development processes. We reanalyzed the three experimental arms of the Individual Screening Trial of Innovative Glioblastoma Therapy (INSIGhT), a randomized phase II platform trial in newly diagnosed O-methylguanine-DNA methyltransferase-unmethylated glioblastoma (ClinicalTrials.gov identifier: NCT02977780). To evaluate the validity of using external data sets, we compared treatment effect estimates based on internal INSIGhT control data and matched external control data. METHODS: The three experimental arms of INSIGhT (abemaciclib [n = 72], neratinib [n = 80], and CC-115 [n = 12]) did not improve survival compared with internal controls (standard chemoradiation [n = 70]). We derived external control patient-level data from multiple real-world and clinical trial data sets. We applied propensity score matching and Cox proportional hazards models to estimate treatment effects with external controls. Additionally, using this glioblastoma (GBM) data collection, we specified simulation scenarios to evaluate trial designs that integrate external controls. RESULTS: After matching to external controls, no survival benefit was observed for patients receiving abemaciclib (hazard ratio [HR], 1.00 [95% CI, 0.75 to 1.34]), neratinib (HR, 0.93 [95% CI, 0.70 to 1.24]), or CC-115 (HR, 0.88 [95% CI, 0.41 to 1.88]). Simulations, together with the INSIGhT data and a collection of GBM data sets, allowed us to examine efficiencies and risks of clinical trial designs that leverage external control data. CONCLUSION: The use of carefully matched external controls, to replace or augment the internal controls of INSIGhT, produced treatment effect estimates that were similar to previously published analyses. Single-arm trial designs and hybrid randomized designs incorporating propensity score-matched external control data evaluated treatment effects in the early-phase testing of experimental therapies in newly diagnosed GBM. The validity of this approach and risks of bias depended on the availability of comprehensive and accurate data on all potential confounders, in the absence of unmeasured confounding.