Many patients with biochemically recurrent prostate cancer (BCRPC) prefer to delay androgen deprivation therapy (ADT) due to its adverse effects, highlighting the need for better-tolerated, effective alternatives. A subgroup analysis of our prior Phase II trial showed that muscadine grape skin extract (MPX) increased PSA doubling time (PSADT) in patients with SOD2 Ala/Ala variant which provided the rationale for this trial.

In patients with acute myeloid leukaemia treated with curative intent, the detection of measurable residual disease (MRD) generally confers a poor prognosis. This study aimed to identify whether altering treatment based on MRD results can improve survival.

The incidence of epidermal growth factor receptor (EGFR) mutations is higher among Asian patients with advanced non-small cell lung cancer than the general advanced non-small cell lung cancer population. We evaluated the efficacy and safety of amivantamab in combination with lazertinib versus osimertinib in Asian participants from the phase 3 MARIPOSA study who had treatment-naïve advanced non-small cell lung cancer with common EGFR mutations.

Innovative oral targeted therapies are warranted for patients with human epidermal growth factor receptor 2 (HER2)-mutant non-small-cell lung cancer (NSCLC). Zongertinib is an oral, irreversible, HER2-selective tyrosine kinase inhibitor that has been shown to have efficacy in persons with advanced or metastatic solid tumors with HER2 alterations in a phase 1 study.

Co-mutational patterns play a role in the clinical outcome of nucleophosmin-1 (NPM1) mutated acute myeloid leukaemia (AML). Tyrosine kinase (TK) related gene mutations are included in these additional mutations, but their impact on prognosis of NPM1-mutated AML is unknown. We analyzed the outcomes of patients with NPM1 AML with TK related mutations treated with intensive chemotherapy in the prospective randomized trial NILG AML 02/06, with regards to NPM1-FLT3-ITD and NPM1-isolated. Data show that additional TK related mutations do not impact the favorable prognosis on NPM1-mutated AML, unlike NPM1-FLT3-ITD mutated AML, for which consolidation with allogeneic stem cell transplantation should be considered for all young and fit patients in first complete remission.

The addition of targeted therapy (TT) to immune checkpoint inhibitors has been shown to transiently increase immune infiltration in melanoma. This formed the rationale for the IMPemBra trial, which showed a numerical increase in progression-free survival (PFS) in patients treated with short-term/intermittent TT and anti-PD1 compared to anti-PD1 alone. In this report, the final toxicity-analysis, 5-year PFS and exploratory analysis of overall survival (OS) will be reported, together with an analysis of subsequent therapies.

The aim of this study was to evaluate the prognostic value of undetectable circulating tumor DNA (ctDNA) and the dose-response relationship between ctDNA levels and survival outcomes in metastatic castration-resistant prostate cancer (mCRPC).

This study investigated the effects of taxane-cisplatin combinations on pathologic complete response (pCR) rates and survival outcomes in triple-negative breast cancer (TNBC).

Identifying patients with inherited colorectal cancer (CRC) syndromes offers many potential benefits. However, individuals often experience decisional conflict regarding genetic testing for CRC, and the uptake rate remains low. Given the growing popularity of genetic testing and the increasing demands on genetic service providers, strategies are needed to promote informed decision-making, increase genetic testing uptake among at-risk individuals, and ensure the rational use of genetic service resources.

Historically, fewer than 10% of adults with cancer have enrolled in clinical trials. Computational tools have been developed to match patients to trials, but these tools are relevant only when patients need new treatment.

Cell-free, circulating tumour DNA (ctDNA) is an established measure of minimal residual disease; however, it is not utilised in melanoma management. We investigated whether ctDNA measurements could predict survival outcomes during adjuvant targeted therapy or placebo treatment in stage III melanoma, thereby identifying patients at high risk and low risk of recurrence.

The rs4680 single-nucleotide polymorphism (SNP) of the COMT gene leads to a reduction in dopamine clearance, resulting in better mood and a decrease in symptoms in noncancer populations, but its influence on quality of life (QOL) during cancer treatment is undefined. We hypothesized that in comparison to wildtype (WT) COMT, the rs4680 SNP is associated with better QOL among men with metastatic hormone-sensitive prostate cancer receiving androgen deprivation therapy ± docetaxel (ADT ± D).

ETV6::RUNX1-positive pediatric acute lymphoblastic leukemia frequently has a prenatal origin and follows a two-hit model: a first somatic alteration leads to the formation of the oncogenic fusion gene ETV6::RUNX1 and the generation of a preleukemic clone in utero. Secondary hits after birth are necessary to convert the preleukemic clone into clinically overt leukemia. However, prenatal factors triggering the first hit have not yet been determined. Here, we explore the influence of maternal factors during pregnancy on the prevalence of the ETV6::RUNX1 fusion. To this end, we employed a nested interventional cohort study (IMPACT-BCN trial), including 1221 pregnancies (randomized into usual care, a Mediterranean diet, or mindfulness-based stress reduction) and determined the prevalence of the fusion gene in the DNA of cord blood samples at delivery (n = 741) using the state-of-the-art GIPFEL (genomic inverse PCR for exploration of ligated breakpoints) technique. A total of 6.5% (n = 48 of 741) of healthy newborns tested positive for ETV6::RUNX1. Our multiple regression analyses showed a trend toward lower ETV6::RUNX1 prevalence in offspring of the high-adherence intervention groups. Strikingly, corticosteroid use for lung maturation during pregnancy was significantly associated with ETV6::RUNX1 (adjusted OR 3.9, 95% CI 1.6-9.8) in 39 neonates, particularly if applied before 26 weeks of gestation (OR 7.7, 95% CI 1.08-50) or if betamethasone (OR 4.0, 95% CI 1.4-11.3) was used. Prenatal exposure to corticosteroids within a critical time window may therefore increase the risk of developing ETV6::RUNX1+ preleukemic clones and potentially leukemia after birth. Taken together, this study indicates that ETV6::RUNX1 preleukemia prevalence may be modulated and potentially prevented.

In the Phase 3 PhALLCON trial (NCT03589326), ponatinib demonstrated superior efficacy and comparable safety profile versus imatinib in adults with newly diagnosed Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL). Here we report patient-reported outcomes (PRO) from PhALLCON assessed as exploratory endpoints using the Functional Assessment of Cancer Therapy-Leukemia (FACT-Leu) and EQ-5D-5L. Primary PRO domains included FACT-G physical well-being, FACT-Leu subscale (FACT-LeuS), Trial Outcome Index (TOI), FACT-Leu total score, FACT-G total score, and EQ-5D visual analogue scale. Differences in least-squares mean score changes from baseline to the end of induction (EOI)/consolidation (EOC) and time to confirmed improvement/deterioration were analyzed. Overall treatment tolerability was assessed using the FACT-GP5. Analyses included 238 patients (ponatinib 159, imatinib 79) with ≥1 PRO assessment. Least-squares mean changes from baseline favored ponatinib, with significant and meaningful differences in FACT-LeuS, TOI, and FACT-Leu total score at EOI and across the primary domains except for FACT-LeuS at EOC. Median time to confirmed improvement was shorter with ponatinib versus imatinib for key measures. Ponatinib-treated patients tended to report being less bothered by treatment side effects as assessed by FACT-GP5. These findings highlight ponatinib's potentially favorable impact on health-related quality of life, supporting its use as frontline treatment for Ph+ ALL.

To our knowledge, the ACHILLES/TORG1834 trial is the first randomized study comparing afatinib and chemotherapy in patients with non-small cell lung cancer (NSCLC) harboring sensitizing uncommon epidermal growth factor receptor (EGFR) mutations.

Molecular diagnostics play a pivotal role in guiding therapy for metastatic colorectal cancer (mCRC). Current guidelines recommend stratification based on biomarkers such as RAS, BRAF, and DNA mismatch-repair (MMR) status to select between anti-EGFR (epidermal growth factor receptor) and anti-VEGF (vascular endothelial growth factor) therapies.

To evaluate the efficacy and safety/tolerability of paclitaxel with and without the AKT inhibitor afuresertib in patients with platinum-resistant ovarian cancer (PROC).

In the phase III CodeBreaK 300 study, sotorasib 960 mg-panitumumab significantly prolonged progression-free survival (PFS) versus investigator's choice (trifluridine/tipiracil or regorafenib) in patients with KRAS G12C-mutated chemorefractory metastatic colorectal cancer (mCRC). One hundred sixty patients were randomly assigned 1:1:1 to receive sotorasib 960 mg-panitumumab (n = 53), sotorasib 240 mg-panitumumab (n = 53), or investigator's choice (n = 54; crossover permitted after primary analysis). Overall survival (OS) analysis, a key secondary end point, although not adequately powered, was prespecified at 50% maturity (after approximately 80 deaths). In this study, we report the OS, updated overall response rates (ORRs), and data for safety. After a median follow-up of 13.6 months, 24, 28, and 30 deaths occurred in the sotorasib 960 mg-panitumumab, sotorasib 240 mg-panitumumab, and investigator's choice arms, respectively; updated objective response rates (ORRs; 95% CI) were 30.2% (95% CI, 18.3 to 44.3), 7.5% (95% CI, 2.1 to 18.2), and 1.9% (95% CI, 0.0 to 9.9), respectively. Compared with investigator's choice, the hazard ratios (HRs [95% CI]) for OS were 0.70 (95% CI, 0.41 to 1.18; two-sided P = .20) with sotorasib 960 mg-panitumumab and 0.83 (95% CI, 0.49 to 1.39; two-sided P = .50) with sotorasib 240 mg-panitumumab. No new safety signals were observed. Although not statistically significant, the observed OS HR and ORR along with prior PFS and safety findings support sotorasib 960 mg-panitumumab as a standard of care in patients with chemorefractory KRAS G12C mCRC.

The PENELOPE-B trial (ClinicalTrials.gov identifier: NCT01864746) recruited patients with hormone receptor+/human epidermal growth factor receptor 2- early breast cancer without a pathological complete response after taxane-containing neoadjuvant chemotherapy and at a high risk of relapse. Patients were randomly assigned (1:1) to receive 13 cycles of palbociclib once daily or placebo on days 1-21 in a 28-day cycle in addition to endocrine therapy (ET). PENELOPE-B did not show improved invasive disease-free survival (iDFS) after adding palbociclib to ET. This retrospective analysis investigated the impact of germline pathogenic variant (PV) status of BRCA1/2 and non-BRCA1/2 cancer predisposition genes on the outcomes of PENELOPE-B trial patients.

With increased demand for cancer genetic testing (GT), providers are exploring alternative service delivery models such as video education (VE). We compare the uptake of GT among 250 patients with breast, ovarian, pancreatic, or metastatic prostate cancer randomly assigned to receive either pretest VE or a pretest visit with a genetic counselor (GC).