The Oncotype DX Recurrence Score's Impact on the Management of Oestrogen-Positive/Human Epidermal Growth Factor Receptor 2-Negative, Low-Burden Axillary Status Breast Cancer (REHAB Study): Results of a Single Centre.

Background The Oncotype DX Recurrence Score (ODX-RS) is increasingly utilized in oestrogen receptor (ER)-positive/human epidermal growth factor receptor 2 (HER2)-negative, low-burden axillary disease early operable breast cancer. It has been demonstrated to predict the benefits of adjuvant chemotherapy, hence supporting individualized decisions on adjuvant therapy. Aim To investigate the application of ODX-RS as an adjuvant treatment decision tool in breast cancer operated in our unit. Methods A total of 107 eligible patients who were operated on between 2017 and 2021 in Basildon University Hospital, UK were enrolled in this study. In this retrospective study, the clinical data, including patient's age, tumour size, ER status, HER2 status, Ki67 proliferative index (Ki67-PI), nodal status, tumour grade, and ODX-RS, were collected. In the study design, the oncologist had the opportunity to assess the need for adjuvant chemotherapy for patients with ER-positive, HER2-negative, low-burden axillary lymph node disease, early breast cancer by using tumour characteristics and the PREDICT tool without knowing the ODX-RS results. The clinician's decision was matched against the breast multidisciplinary team's recommendations after ODX-RS utilisation, and the results were explored. Results The median ODX-RS of cohort tumours was 18 in the age group > 50 years, with ODX-RS ≥ 26 found in 18% of the group (n = 12). In the age group ≤ 50 years, 17% (n = 7) had ODX-RS between 21 and 25 and only 7% (n = 3) had ODX-RS ≥ 26. Without using ODX-RS, only 16% of the patients had been offered adjuvant chemotherapy in addition to the hormonal manipulation therapy; however, after using ODX-RS, up to 33% of the cohort was suitable for adjuvant chemotherapy in addition to the hormonal manipulation therapy. The changes in the recommendations after ODX-RS utilisation have been noticed in 29% of the cohort. Conclusion This study revealed that ODX-RS supported decision-making regarding postoperative adjuvant chemotherapy, especially when other tumour biomarkers, such as tumour size, grading, or Ki-67, indicated lower risk criteria. Patients with a high ODX-RS were offered chemotherapy where appropriate and its use led to a 15% rate of initial decision change in adjuvant treatment decisions; this involved either recommending chemotherapy or its omission.

Target-based therapeutic matching of phase I trials in patients with metastatic breast cancer in a tertiary referral centre.

BACKGROUND: Greater understanding of the molecular classification of breast cancer has permitted the development of rational drug design strategies. In a phase I clinical trial setting, molecular profiling with next-generation sequencing of individual tumour samples has been employed to guide treatment. METHODS: We conducted a retrospective evaluation of clinical outcomes of patients with metastatic breast cancer (MBC) treated in phase I clinical trials at our institution to assess the benefit of molecularly matched compared to non-matched treatments. RESULTS: A total of 97 consecutive patients with MBC were enrolled onto ≥1 trial between 2009 and 2015. Fourteen patients participated in multiple trials, and a total of 113 trial encounters were reviewed in this retrospective study. Eighty-three percent of patients with molecular data available were able to participate in trials matched to molecular aberrations. Patients who were treated on matched studies had improved clinical benefit (RR: 1.80, p = 0.005), progression-free (HR: 0.52, p = 0.003) and overall survival (HR: 0.54, p < 0.001). Treatment was well tolerated with low rates of treatment discontinuation for toxicity (8% overall) that did not differ between groups. No toxicity-related deaths were observed. CONCLUSIONS: Molecular profiling for MBC patients in a phase I setting is feasible and aids therapeutic decisions with improved patient outcomes.

Clinical outcomes and prognostic factors of patients with advanced mesothelioma treated in a phase I clinical trials unit.

BACKGROUND: We have previously reported a prognostic score for patients in phase I trials in the Drug Development Unit, treated at the Royal Marsden Hospital (RPS). The RPS is an objective tool used in patient selection for phase I trials based on albumin, number of disease sites and LDH. Patients with mesothelioma are often selected for phase I trials as the disease remains localised for long periods of time. We have now reviewed the clinical outcomes of patients with relapsed malignant mesothelioma (MM) and propose a specific mesothelioma prognostic score (m-RPS) that can help identify patients who are most likely to benefit from early referral. METHODS: Patients who participated in 38 phase I trials between September 2003 and November 2015 were included in the analysis. Efficacy was assessed by response rate, median overall survival (OS) and progression-free survival (PFS). Univariate (UVA) and multivariate analyses (MVA) were carried out to develop the m-RPS. RESULTS: A total of 65 patients with advanced MM were included in this retrospective study. The PFS was 2.5 months (95% confidence interval [CI] 2.0-3.1 months) and OS was 8 months (95% CI 5.6-9.8 months). A total of four (6%) patients had RECIST partial responses, whereas 26 (40%) patients had RECIST stable disease >3 months. The m-RPS was developed comprising of three different prognostic factors: a neutrophil: lymphocyte ratio greater than 3, the presence of more than two disease sites (including lymph nodes as a single site of disease) and albumin levels less than 35 from the MVA. Patients each received a score of 1 for the presence of each factor. Patients in group A (m-RPS 0-1; n = 35) had a median OS of 13.4 months (95% CI 8.5-21.6), whereas those in group B (m-RPS 2-3; n = 30) had a median OS of 4.0 months (95% CI 2.9-7.1, P < 0.0001). A total of 56 (86%) patients experienced G1-2 toxicities, whereas reversible G3-4 toxicities were observed in 18 (28%) patients. Only 10 (15%) patients discontinued phase I trials due to toxicity. CONCLUSIONS: Phase I clinical trial therapies were well tolerated with early signals of antitumour activity in advanced MM patients. The m-RPS is a useful tool to assess MM patient suitability for phase I trials and should now be prospectively validated.

Metastatic melanoma: a regional review and future directions.

AIMS AND BACKGROUND: . The incidence of malignant melanoma has risen steadily over recent decades. NCI data from 2005-2007 have suggested that 1.93% of individuals born today in the US will develop melanoma at some stage. Approximately 15% of patients with MM either present with metastatic disease or develop metastases during the course of their illness. Unfortunately, metastatic MM remains a challenge with limited treatment options, and median overall survival is 6-9 months. METHODS: We reviewed our data for the treatment of metastatic MM over a period of four years. Data from all patients with metastatic MM treated with systemic therapy without clinical trials from 2006 to 2009 were reviewed. Response rate was determined as per RECIST criteria. RESULTS: Sixty four patients were treated with one or more lines of cytotoxic therapy. Median age was 62 years (range, 23-82) with 53% males. Primary site of the disease was the skin in 75%, mucosal in 12.5%, ocular in 9.4% and nodal with an occult primary in 3.1%. Visceral metastases were present in 75% of patients at the start of treatment, including pulmonary (39.6%) and hepatic (34.4%). All patients were screened for brain metastases, which were present in 26.5% of patients. ECOG performance status was 0 in 7.8%, 1 in 68.7%, 2 in 9.4% and undocumented in the remaining 14%. Patients without brain metastases received single agent DTIC as first line; those with brain metastases received temozolomide. Response rate was 7% for DTIC and 28% for temozolomide, with median progression-free survival of 2.4 and 3.2 months, respectively. Seven patients who received DTIC are alive on follow-up, 2 have ongoing stable disease post-DTIC at 41 months and 18 months. Second line therapy with vinblastine was given to 21 patients (32%), with a response rate of 9.5% and median progression-free survival of 3.4 months. Median overall survival from initiation of therapy was 7.7 months for DTIC and 3.6 months for patients with brain metastases receiving temozolomide. A performance status of 2 was associated with shorter median overall survival (2.0 months). CONCLUSIONS: . Our results are comparable to published data. Malignant melanoma is a disease with rising incidence and limited treatment options. These patients are best treated in the context of clinical trials as new targeted therapies are promising as future strategies.