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).

Adjuvant osimertinib is the standard of care for patients with resected epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC). Neoadjuvant treatment could improve surgical and long-term outcomes.

Vepdegestrant is an oral proteolysis-targeting chimera (PROTAC) estrogen receptor (ER) degrader that directly harnesses the ubiquitin-proteasome system.

In the phase 3, double-blind, randomized INAVO120 trial, treatment with inavolisib plus palbociclib-fulvestrant led to a significant progression-free survival benefit, as compared with placebo plus palbociclib-fulvestrant, among patients with PIK3CA-mutated, hormone receptor-positive, human epidermal growth factor receptor 2 (HER2)-negative locally advanced or metastatic breast cancer who had had relapse during or within 12 months after completion of adjuvant endocrine therapy.

Mutations in ESR1 are the most common mechanism of acquired resistance to treatment with an aromatase inhibitor plus a cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitor for advanced breast cancer. Camizestrant, a next-generation selective estrogen-receptor (ER) degrader and complete ER antagonist, has shown antitumor activity in ER-positive advanced breast cancer.

Current first-line treatment for patients with metastatic melanoma with BRAFV600E or BRAFV600K mutations includes immunotherapy with immune checkpoint inhibitors and targeted therapy; however, the optimal sequencing of these treatments is unclear. We aimed to investigate the use of a targeted-therapy induction regimen before treatment with immune checkpoint inhibitors.

Black males have low rates of genetic testing for prostate cancer (PCa). Peer-based strategies have not been tested for PCa genetic testing. We aimed to evaluate the impact of a peer-based educational intervention about PCa genetic testing for Black males in a community setting.

Gastrointestinal stromal tumours (GIST) are driven by mutations in KIT and platelet derived growth factor receptor A (PDGFRA) kinases in >75% of patients. Imatinib, a tyrosine kinase inhibitor, has shown efficacy in metastatic GIST but the long-term survival impact remains less understood, especially after extended treatment durations.

The phase III CheckMate 9LA study demonstrated durable overall survival (OS) benefit with nivolumab plus ipilimumab with chemotherapy versus chemotherapy in patients with metastatic non-small-cell lung cancer (NSCLC). Here, we report final, 6-year efficacy and safety outcomes.

The aim of this study was to investigate the association between Interleukin-8 (IL-8) rs4073 polymorphism and oral mucositis (OM).

First-line treatment with encorafenib plus cetuximab (EC) with or without chemotherapy (oxaliplatin, leucovorin, and fluorouracil [mFOLFOX6]) for BRAF V600E-mutated metastatic colorectal cancer, an aggressive subtype with a poor prognosis, was compared with standard care (chemotherapy with or without bevacizumab) in an open-label, phase 3 trial, which showed significance regarding one of the two primary end points, objective response according to blinded independent central review (odds ratio for EC+mFOLFOX6 vs. standard care, 2.44; one-sided P<0.001). This result led to accelerated Food and Drug Administration approval of this investigational combination therapy for BRAF V600E-mutated metastatic colorectal cancer, including as first-line therapy. Data on progression-free survival (the second primary end point) and an updated interim analysis of overall survival are now available.

The ASTRUM-005 study previously demonstrated a significant overall survival (OS) benefit with serplulimab (a programmed death 1 inhibitor) plus chemotherapy versus chemotherapy alone in previously untreated extensive-stage small-cell lung cancer (ES-SCLC). Here, we report updated efficacy and safety results after an extended median follow-up of 19.8 months, along with the first report on findings from exploratory biomarker analyses.