Durvalumab in combination with chemoradiotherapy in patients with head and neck squamous cell carcinoma: Results from the Phase 1 CLOVER study.

Background: The Phase 1 CLOVER study (NCT03509012) assessed durvalumab in combination with concurrent chemoradiotherapy (cCRT) in patients with advanced solid tumors; we report results from the head and neck squamous cell carcinoma (HNSCC) cohort.

Methods: Patients with histologically/cytologically confirmed locally advanced HNSCC, eligible for definitive cCRT and not considered for primary surgery, received durvalumab plus cisplatin and concurrent external beam radiation. Objectives were to assess safety/tolerability and preliminary efficacy.

Design and Rationale for a Phase III, Randomized, Placebo-controlled Trial of Durvalumab With or Without Tremelimumab After Concurrent Chemoradiotherapy for Patients With Limited-stage Small-cell Lung Cancer: The ADRIATIC Study.

Limited-stage (LS) small-cell lung cancer (SCLC) remains an area of high unmet medical need. The standard-of-care therapy comprises curative-intent platinum-based chemotherapy with concurrent radiotherapy (cCRT), which can be followed by prophylactic brain irradiation and then observation. However, most patients will relapse.

Prospective analysis of 895 patients on a UK Genomics Review Board.

Background: The increasing frequency and complexity of cancer genomic profiling represents a challenge for the oncology community. Results from next-generation sequencing-based clinical tests require expert review to determine their clinical relevance and to ensure patients are stratified appropriately to established therapies or clinical trials.

Methods: The Sarah Cannon Research Institute UK/UCL Genomics Review Board (GRB) was established in 2014 and represents a multidisciplinary team with expertise in molecular oncology, clinical trials, clinical cancer genetics and molecular pathology.

A phase Ib dose-finding, pharmacokinetic study of the focal adhesion kinase inhibitor GSK2256098 and trametinib in patients with advanced solid tumours.

Background: Combined focal adhesion kinase (FAK) and MEK inhibition may provide greater anticancer effect than FAK monotherapy.

Methods: This dose-finding phase Ib study (adaptive 3 + 3 design) determined the maximum tolerated dose (MTD) of trametinib and the FAK inhibitor GSK2256098 in combination. Eligible patients had mesothelioma or other solid tumours with probable mitogen activated protein kinase pathway activation.

Dynamics of Neutrophils-to-Lymphocyte Ratio Predict Outcomes of PD-1/PD-L1 Blockade.

Introduction: Baseline neutrophil-to-lymphocyte ratio (NLR) has been repeatedly reported as a significant prognostic factor in advanced cancer patients. We explored whether changes in NLR may predict outcome of advanced cancer patients enrolled into phase 1 trials and treated with PD-1/PD-L1 inhibitors.

Patients And Methods: Advanced cancer patients enrolled into phase 1 trials between September 2013 and May 2016 and treated with anti-PD-1/PD-L1 agents were included in this retrospective study.

Evaluation of the effect of dabrafenib and metabolites on QTc interval in patients with BRAF V600-mutant tumours.

Aims: The effect of repeat oral supratherapeutic dosing of the BRAF inhibitor dabrafenib on QTc interval was assessed in patients with BRAF V600-mutant tumours.

Methods: Part 1 of this phase 1, multicentre, 2-part study (BRF113773/NCT01738451) assessed safety/tolerability of dabrafenib 225 or 300 mg twice daily (BID) to inform part 2 dosing. Patients in part 2 received dabrafenib-matched placebo on day -1, single-dose dabrafenib 300 mg on day 1, 300 mg BID on days 2 to 7, and 300 mg on day 8 (morning), followed by 24-h Holter electrocardiographic monitoring and pharmacokinetics sample collection each dose day.

Dabrafenib and trametinib activity in a patient with BRAF V600E mutated and microsatellite instability high (MSI-H) metastatic endometrial cancer.

Background: Targeting BRAF V600E mutation has been proven effective in the treatment of several types of cancer. In endometrial adenocarcinoma, the BRAF V600E mutation has been rarely reported. Whether targeting BRAF oncogene may represent a plausible therapeutic strategy for the rare patients with BRAF-mutated endometrial cancer remains to be ascertained in prospective studies.

The Impact of Mismatch Repair Status in Colorectal Cancer on the Decision to Treat With Adjuvant Chemotherapy: An Australian Population-Based Multicenter Study.

Background: Testing for mismatch repair (MMR) status in colorectal cancer (CRC) may provide useful prognostic and predictive information. We evaluated the impact of such testing on real-world practice regarding adjuvant chemotherapy for patients with resected CRC.

Patients And Methods: A total of 175 patients with stage II and III mismatch repair-deficient (MMRD) CRC were identified from an Australian population-based study of incident CRCs.

Cutaneous metastasis of prostate carcinoma treated with radiotherapy: a case presentation.

Background: Prostate cancer is a commonly diagnosed and treated malignancy, although it rarely presents with cutaneous metastases. In this case presentation, we describe the diagnosis and treatment with radiotherapy of a patient who presented with cutaneous metastases on his chest wall secondary to prostate cancer.

Case Presentation: In 2006, a 73-year-old Caucasian gentleman with metastatic castration resistant prostate cancer treated with mitoxantrone and prednisolone presented with cutaneous nodules on his chest wall.

Resistance surveillance in a BRAF mutant melanoma patient on long-term BRAF-inhibitor treatment.

Treatment responses of BRAF mutant melanoma to BRAF inhibitors are often limited by the development of resistance. This case report describes the use of multiplatform molecular profiling in sequential surgical samples of a treatment-resistant tumour site subjected to ongoing treatment with dabrafenib in a patient with metastatic cutaneous BRAF mutant melanoma. Next-generation sequencing showed the presence of the V600E, fibroblast growth factor receptor 2 (FGFR2), phosphatase and tensin homologue (PTEN) and p53 gene mutations.

Use of neostigmine in capecitabine-induced paralytic ileus.

Paralytic ileus is a recognised side effect of the oral agent capecitabine. We present this report on a patient with metastatic colorectal cancer who was treated with capecitabine and presented with persistent paralytic ileus which did not respond to standard conservative measures. Neostigmine was administered safely, resulting in resolution of the paralytic ileus.