Osimertinib is the standard first-line options for patients with advanced EGFR-mutated non-small cell lung cancer (NSCLC). Co-mutations in TP53 results in poor survival for patients. However, the studies on treatment options and clinical outcomes of patients with EGFR-TP53 co- mutation are limited. Patients with EGFR mutation-positive locally advanced or metastatic NSCLC carrying TP53 mutations were recruited from two institutions and randomly allocated into two groups, either receiving osimertinib plus chemotherapy (Osi + Chemo group) or osimertinib monotherapy (Osi group). The progression-free survival (PFS) was evaluated as the primary endpoint and the response was also assessed. Between January 2020 and August 2023, ninety-eight patients were enrolled with 47 and 51 patients receiving combination therapy and the monotherapy. After a median follow-up of 19.2 months, overall response rate (ORR) was 80.0% vs. 71.7% (p = 0.36), favoring Osi + Chemo group, as well as in disease control rate (DCR) (91.4% vs. 80.4%, p = 0.45). The median PFS in the Osi + Chemo group was 26.0 months versus 20.7 months in the Osi group, but there was no significant difference (p = 0.34). The subgroup analysis indicated that for patients with L858R mutation, Osi + Chemo therapy significantly prolonged the median PFS (not reached [NR] versus 17.1 months, p = 0.03), but showed no benefit in patients with 19Del (20.6 months versus NR, p = 0.31). Osimertinib plus chemotherapy has a tendency to increase ORR and prolong PFS in NSCLC with EGFR and TP53 co-mutations, particularly in patients with L858R mutation.

In urothelial carcinoma, prior studies have indicated that the basal/squamous molecular subtype and the presence of select DNA damage response (DDR) gene alterations are associated with improved benefit from cisplatin-based chemotherapy. We sought to evaluate these biomarkers in specimens from the phase III Cancer and Leukemia Group B (CALGB) 90601 trial.

Trastuzumab combined with chemotherapy is a standard treatment for human epidermal growth factor receptor 2 (HER2)-positive advanced breast cancer in later lines. Lapatinib and trastuzumab have also demonstrated efficacy. This study assessed the efficacy, toxicity, and quality of life (QoL) of trastuzumab plus lapatinib (with endocrine therapy for hormone receptor-positive cases) versus trastuzumab with physician-selected chemotherapy in patients previously treated with at least 2 anti-HER2 regimens.

We conducted a post hoc analysis of data from Blood and Marrow Transplant Clinical Trials Network 1506 (MORPHO), a randomized trial of gilteritinib vs placebo as posttransplantation maintenance for patients with FLT3-ITD-mutated acute myeloid leukemia (AML) undergoing allogeneic hematopoietic cell transplantation (HCT), focusing the interactions between conditioning regimen intensity, measurable residual disease (MRD), and NPM1 comutation status reported from diagnosis. Comparing FLT3-ITD MRD before and after conditioning, there was no difference between myeloablative conditioning (MAC) and reduced-intensity conditioning (RIC) in eradication or reduction of FLT3-ITD MRD. For participants who were FLT3-ITD MRD negative before HCT, there was no difference in the cumulative incidence of relapse during follow-up between those receiving MAC vs RIC. NPM1 comutation was associated with the largest magnitude of relapse-free survival benefit from post-HCT gilteritinib, and in these participants, post-HCT gilteritinib in the setting of RIC appeared to be as effective as MAC at preventing relapse. MAC appeared superior to RIC in preventing relapse only in participants who were NPM1 wild type at diagnosis and FLT3-ITD MRD positive before HCT. Our findings suggest that only a subset of patients with FLT3-ITD AML undergoing HCT may benefit from MAC and that, similar to AML therapy before HCT, the intensity of the HCT regimen should be adapted according to the molecular features of the disease. This trial was registered at www.clinicaltrials.gov as #NCT02997202.

The use of commercially available comprehensive genomic profiling tests, such as the FoundationOne CDx (F1CDx), has increased. However, the success rate of F1CDx using samples obtained by EUS-guided tissue acquisition (EUS-TA) is suboptimal. This study aimed to verify the optimal method for obtaining samples suitable for F1CDx among 3 EUS-TA techniques.

Brigatinib, a selective ALK inhibitor, demonstrated preclinical activity against a range of crizotinib-resistant ALK alterations in NSCLC. We examined associations between brigatinib efficacy and tumor- and plasma-detected driver mutations in crizotinib-resistant ALK fusion-positive NSCLC.

In ARIEL3, rucaparib maintenance significantly improved progression-free survival (PFS; primary endpoint) and long-term follow-up (LTFU) outcomes (including PFS2: time to disease progression on subsequent therapy or death) versus placebo in patients with recurrent, platinum-sensitive ovarian cancer. Here we report the final analysis of overall survival (OS; key secondary endpoint), LTFU outcomes, and safety.

Germline pharmacogenetics (PGx) is increasingly used to tailor medication selection/dosing. However, existing systems primarily communicate PGx results to providers, limiting direct patient engagement. To address this, we developed YourPGx Oncology, an innovative patient-facing portal that delivers multi-gene PGx results (CYP2D6, UGT1A1, DPYD) through 33 unique, patient-friendly summaries. The utility of this tool was prospectively evaluated in an oncology population, where these pharmacogenes impact high-stakes treatments. Patients enrolled in the PhOCus study (NCT04541381) participated in single-session evaluations of the tool in-person or via videoconference, with a pharmacist available for questions and administering pre- and post-surveys that assessed educational impact. Each patient viewed their own previously obtained PGx results. Of 190 eligible patients, 70 responded to solicitations via email, phone, and in-person, of whom 51 (73%) completed an observed session and completed surveys. Patients spent a median of 13.4 minutes (range 8.1-21.0) navigating YourPGx Oncology. After portal interaction, patients' ability to identify individual efficacy and safety estimates for chemotherapies and pain medications significantly improved, with the proportion accurately recognizing PGx-informed drug efficacy likelihoods rising from 32% to 72% (Odds Ratio [OR] = 5.8 for the shift from discordant to concordant efficacy knowledge, P < 0.001), and PGx-related toxicity recognition increasing from 31% to 57% (OR = 3.2, P = 0.01). Our findings show that a customized patient-facing PGx results portal enhances patient understanding of individual medication efficacy and toxicity likelihoods, highlighting the potential key role of direct-to-patient PGx tools to facilitate optimized treatment-informed care and promote genetically guided shared decision-making.

Survival for non-small-cell lung cancer (NSCLC) remains unacceptably low, even in stage IA-IIA. Current guidelines recommend adjuvant treatment for patients considered to be at high risk in stages IB and IIA, but suggest criteria that have not been validated to predict benefit. A previously validated, CLIA-certified 14-gene expression profile has identified patients with high-risk non-squamous NSCLC tumours in stages IA-IIA who benefitted from adjuvant chemotherapy in a non-randomised prospective study. In this prespecified interim analysis, we aimed to assess the efficacy and safety of platinum-based adjuvant chemotherapy in patients with stage IA-IIA molecular high-risk non-squamous NSCLC in a randomised trial.

The combination of FOLFOX/FOLFIRI with an EGFR-antibody (cetuximab/panitumumab) is a first-line standard for RAS wild-type metastatic colorectal cancer (mCRC). The OPTIMOX stop-and-go regimen, which reduces oxaliplatin-induced neuropathy, and fluorouracil/folinic acid (FU/FA) were standard maintenance-therapies in the pre-antibody era. Whether an EGFR-antibody adds value to the OPTIMOX strategy in the RAS wild-type setting remains unknown.

In a prespecified GEICAM_CIBOMA trial (NCT00130533) correlative analysis, PAM50 non-basal-like breast cancer (non-BLBC) status distinguished patients with triple-negative breast cancer (TNBC) who are most likely to benefit from adjuvant capecitabine. The standardized forkhead box C1 (FOXC1) IHC test has demonstrated strong reliability in classifying the BLBC subtype throughout TNBC cohorts. This translational analysis aimed to evaluate the prognostic/predictive significance of BLBC classification by FOXC1 IHC in the phase III GEICAM_CIBOMA clinical trial.

Biomarker-guided therapies are needed for patients with refractory metastatic colorectal cancer (mCRC). Liquid biopsy (LBx) circulating tumor DNA (ctDNA) comprehensive genomic profiling (CGP) could contribute to the clinical tailoring of molecular targeted therapies for these patients.

Limertinib is a new third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor. This study aimed to prospectively assess the efficacy and safety of limertinib versus gefitinib as a first-line treatment for locally advanced or metastatic non-small-cell lung cancer (NSCLC) with EGFR-sensitising mutation.

Therapeutic responses in acute myeloid leukemia (AML) demonstrate considerable variability both across and within established risk stratifications and age groups. Moreover, significant racial disparities persist, with Black patients experiencing inferior survival outcomes compared with their White counterparts.

Statistically standardized estrogen receptor (ER) and progesterone receptor (PgR) differentiated prognosis. Here we examined statistically standardized human epidermal growth receptor 2 (HER2).

Neoadjuvant immunotherapy is a first-line treatment for recurrent and metastatic head and neck squamous cell carcinoma (HNSCC). However, only a fraction of patients with advanced HNSCC benefit from immunotherapy. Identifying accurate and accessible biomarkers is essential for optimal patient selection. In this study, we integrated single-cell RNA sequencing and T-cell receptor sequencing to comprehensively characterize the tumor immune microenvironment (TIME) of HNSCC biopsies prior to a phase II neoadjuvant immunotherapy clinical trial. Tumor-specific MHC-II (tsMHC-II) was identified as a superior predictor of response to neoadjuvant immunotherapy in HNSCC compared with PD-L1. Mechanistically, tsMHC-II ignited a hot TIME and enhanced the effect of PD-1 blockade by recruiting T cells through the induction of chemokines, particularly CCL5. Moreover, tsMHC-II triggered a Th1 response and activated CD4+ and CD8+ T-cell expansion, suppressing HNSCC growth in a CD4+ T-cell-dependent manner. Simultaneously, tsMHC-II facilitated an increase in PD-1+CD4+ T cells and a modest elevation in tumor PD-L1, thereby enhancing sensitivity to anti-PD-1 therapy. This study highlights that tsMHC-II, by generating an inflamed TIME, is crucial in enhancing the effectiveness of neoadjuvant immunotherapy in HNSCC.

Immune checkpoint inhibitors (ICIs) have dramatically transformed the therapeutic landscape of deficient mismatch repair/microsatellite unstable-high (dMMR/MSI-H) metastatic colorectal cancer (mCRC); however, ICI use is challenged by primary resistance and timing of discontinuation. Whether circulating tumor DNA (ctDNA) may be predictive of progression-free survival (PFS) and overall survival (OS) in this treatment context remains unknown.

This exploratory analysis assessed datopotamab deruxtecan (Dato-DXd) in pretreated patients with advanced or metastatic NSCLC and EGFR mutations.

In high-grade serous ovarian cancer (HGSOC) bevacizumab (bev)/olaparib (ola) maintenance was approved for patients with homologous recombination DNA repair deficiency (HRD+) tumors. Although different methods exist to score genomic instability, DNA quality, tumor cell content, and costs may impair our ability to identify patients that will benefit from treatment.

Prophylactic treatment with oral minocycline or doxycycline, moisturizers, and sunscreens has been reported to be beneficial for acneiform rash (AfR) caused by epidermal growth factor receptor (EGFR) inhibitors. It is desirable to predict which patients may develop severe AfR and provide prophylactic treatment. This study aimed to evaluate the association between the worst grade of facial AfR (FAfR) after initiating therapy with EGFR inhibitors and the characteristic skin type in patients with RAS wild-type metastatic colorectal cancer enrolled in the FAEISS study (a phase III, open-label, randomized trial evaluating topical corticosteroids for Facial Acneiform dermatitis by EGFR Inhibitors: Stepwise rank down from potent corticosteroids). Using pretreatment photographs of the face, characteristic skin types, including enlarged pores, oiliness (greasiness), and skin color/redness, were graded on a scale of 1-3. Grade 2 or higher FAfR developed in 9.1%, 27.0%, and 45.8% of patients with enlarged pore scores of 1, 2, and 3, respectively. Patients with enlarged pores tended to have more severe FAfR (p = 0.0216). Moreover, the disease control rate (complete remission/partial remission/stable disease) of the primary disease was seen in 59.1%, 70.6%, and 87.0% of patients with an enlarged pore score of 1, 2, and 3, respectively, showing a statistically significant trend (p = 0.038). This study suggests that a facial skin type with a high number of enlarged pores may be a marker for predicting AfR risk due to anti-EGFR antibody therapy and better therapeutic effects for RAS wild-type metastatic colorectal cancer.