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.

After chemoradiotherapy (CRT), 30%-50% of patients with locally advanced cervical cancer (LACC) relapse, highlighting the unmet need for prognostic biomarkers. In the global randomized CALLA trial (NCT03830866), the addition of durvalumab during and after CRT did not significantly improve progression-free survival (PFS) in a biomarker-unselected intent-to-treat population. We analyzed the association of ultrasensitive circulating tumor DNA (ctDNA) and circulating human papillomavirus (cHPV) DNA detection with relapse and survival in the largest dataset in LACC to date.

Patients with follicular lymphoma who experience disease progression within 24 months of diagnosis (POD24) have a lower survival. Positron emission tomography (PET) response and circulating tumor DNA (ctDNA) minimal residual disease (MRD) assessment at end of induction (EOI) may allow their early identification. A representative cohort of 141 patients from the RELEVANCE phase 3 trial with both available serum samples for ctDNA testing and PET images at randomization and at EOI (week 24) was investigated. Twelve percent were POD24. ctDNA was analyzed using a customized 130-kilobase capture panel, with phased variant (PV) enriched regions representing 39% of the panel. ctDNA was detected in 140 patients (99.3%) at baseline. To optimize specificity, only PVs, found in 124 patients (88%), were considered for ctDNA MRD assessment at EOI. Median progression-free survival (PFS) from EOI was not reached (NR) for the 112 patients with undetected ctDNA at EOI vs 17.7 months (95% confidence interval [CI], 1.4 to NR) for patients with positive ctDNA (MRD+) (P = .0038). Similarly, median PFS was NR for the 104 patients with undetected disease on PET at EOI vs 28.3 months (95% CI, 2.9 to NR; P = .0002) for patients with PET positivity. Both tests had a negative predictive value (NPV) of >90% for POD24. The positive predictive value was 58.3% for ctDNA MRD and 45% for PET but increased to 85.7% when both parameters were combined, without alteration of NPV. These data show that the combination of PET response and ctDNA MRD at EOI allows an early prediction of POD24, which may lead to a preemptive treatment decision. This trial was registered at www.clinicaltrials.gov as #NCT01650701.

To examine whether patient sociodemographic and clinical characteristics and prior interactions with the healthcare system were associated with opening patient portal messages related to cancer genetic services and beginning services.

Proteogenomic analysis is applied to samples from the CALGB 40601 (Alliance) randomized neoadjuvant trial of trastuzumab, lapatinib, or the combination to identify biomarkers associated with pathological response status. Absence of ERBB2 gene amplification and human epidermal growth factor receptor 2 (HER2) protein overexpression by proteogenomics is associated with non-pathological compete response (pCR) (p < 0.05), highlighting potential false positives from standard diagnostics. Pathway analysis in proteogenomics-confirmed HER2+ samples identifies elevated epithelial-mesenchymal transition (EMT) and WNT-β-catenin signaling in non-pCR cases before treatment. Twenty-four pCR-associated proteins reproduce in a second proteomic dataset, and four (GPRC5A, TPBG, SP140L, and NEU1) are significant in a third. A meta-analysis of ten diverse neoadjuvant anti-HER2 treatment regimens from four independent studies confirms that non-pCR cases express higher levels of mRNA for G protein-coupled receptor class C group 5 member A (GPRC5A, p = 0.0002) and trophoblast glycoprotein (TPBG, p = 0.00008). Thus, proteogenomic analysis identifies negative biomarkers for pCR and alternative plasma membrane targets for treatment-resistant HER2+ breast cancer. This trial is registered at clinicaltrials.gov (NCT00770809).

To compare the efficacy and safety of sacituzumab tirumotecan (sac-TMT) with docetaxel in patients with locally advanced or metastatic epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC) after previous treatment failure with EGFR-tyrosine kinase inhibitors and platinum based chemotherapy.

Previously published results demonstrated that the randomized phase 3 IMpassion031 trial met its primary objective: adding atezolizumab to neoadjuvant chemotherapy significantly improved pathologic complete response (pCR) rate in patients with stage II/III triple-negative breast cancer (TNBC). Here we report the prespecified final analysis of the secondary endpoints with 3 years' follow-up, together with exploratory analyses of circulating tumor (ct)DNA. Patients with previously untreated stage II/III TNBC enrolled in 75 academic and community sites in 13 countries were randomized 1:1 to receive neoadjuvant chemotherapy with either peri-operative atezolizumab (n = 165) or preoperative placebo (n = 168). Descriptive secondary endpoints included event-free, disease-free and overall survival. Long-term outcomes favored the atezolizumab group (event-free survival hazard ratio (HR), 0.76; 95% confidence interval (CI), 0.47-1.21; disease-free survival HR, 0.76; 95% CI, 0.44-1.30; overall survival HR, 0.56; 95% CI, 0.30-1.04). Among patients without pCR, 14 of 70 (20%) atezolizumab-treated and 33 of 99 (33%) placebo-treated patients received additional adjuvant therapy, frequently capecitabine. In exploratory biomarker analyses, patients with baseline ctDNA-negative status (6%) had excellent long-term outcomes. Most patients (87%) had cleared ctDNA at surgery. ctDNA-positive status at surgery identified a subset of non-pCR patients with poorest prognosis. Long-term safety was consistent with primary results. These data show that adding atezolizumab to chemotherapy for stage II/III TNBC is associated with favorable long-term outcomes, and ctDNA dynamics provide prognostic value beyond pCR. ClinicalTrials.gov identifier: NCT03197935 .

This study aimed to investigate whether probiotics can ameliorate the H. pylori-induced Wnt/β-catenin-related COX-2 carcinogenesis signaling pathway by regulating the expression of microRNAs (miRNAs).

MET-based resistance following osimertinib treatment for epidermal growth factor receptor (EGFR)-mutated advanced non-small cell lung cancer (NSCLC) is common. We report the primary analysis of the phase II SAVANNAH study (NCT03778229) evaluating savolitinib plus osimertinib in this setting.

OVATION-2, a randomized, controlled, open label phase 1/2 study, evaluated the safety and efficacy of IMNN-001, an IL-12 immune gene therapy, with neo/adjuvant chemotherapy (N/ACT) compared to N/ACT in newly-diagnosed advanced epithelial ovarian cancer (EOC).