Author Correction: HER kinase inhibition in patients with HER2- and HER3-mutant cancers.

The 'Competing interests' statement of this Article has been updated; please see the accompanying Amendment. The original Article has not been corrected online.

HER kinase inhibition in patients with HER2- and HER3-mutant cancers.

Somatic mutations of ERBB2 and ERBB3 (which encode HER2 and HER3, respectively) are found in a wide range of cancers. Preclinical modelling suggests that a subset of these mutations lead to constitutive HER2 activation, but most remain biologically uncharacterized. Here we define the biological and therapeutic importance of known oncogenic HER2 and HER3 mutations and variants of unknown biological importance by conducting a multi-histology, genomically selected, 'basket' trial using the pan-HER kinase inhibitor neratinib (SUMMIT; clinicaltrials.gov identifier NCT01953926). Efficacy in HER2-mutant cancers varied as a function of both tumour type and mutant allele to a degree not predicted by preclinical models, with the greatest activity seen in breast, cervical and biliary cancers and with tumours that contain kinase domain missense mutations. This study demonstrates how a molecularly driven clinical trial can be used to refine our biological understanding of both characterized and new genomic alterations with potential broad applicability for advancing the paradigm of genome-driven oncology.

Ofranergene obadenovec (VB-111) in platinum-resistant ovarian cancer; favorable response rates in a phase I/II study are associated with an immunotherapeutic effect.

OBJECTIVE: Report final results of a phase I/II study of VB-111, a targeted anti-cancer gene therapy with a dual mechanism: anti angiogenic/vascular disruption and induction of an anti-tumor directed immune response, in combination with paclitaxel in patients with platinum-resistant ovarian cancer. METHODS: Study NCT01711970 was a prospective, open label, dose escalation study assessing combination treatment of VB-111 and weekly paclitaxel. In the Phase I part of the study, patients were treated with escalating doses of intravenous VB-111 and paclitaxel. In Phase 2, patients were treated with therapeutic doses of VB-111 and paclitaxel 80 mg/m2. Assessments included safety, overall survival (OS), progression free survival (PFS), and tumor response (CA-125 and RECIST). RESULTS: 21 patients with recurrent platinum-resistant ovarian cancer were enrolled. 17/21 received the therapeutic dose. Patients had a median of 3 prior lines of therapy. Half of the subjects were platinum refractory, and half were previously treated with antiangiogenics. No DLTs were observed. VB-111 was well tolerated and associated with mild flu-like symptoms. In the therapeutic dose cohort, a 58% CA-125 GCIG response rate was seen in evaluable patients. The median OS was 16.6 months in patients treated with therapeutic dose compared to 5.8 months in sub-therapeutic dose (p = 0.028). Tumor specimens taken after treatment demonstrated tumor infiltrated with cytotoxic CD8 T-cells in regions of apoptotic cancer cells. CONCLUSIONS: Treatment with VB-111 in combination with paclitaxel was safe and well tolerated. Favorable tumor responses and overall survival outcomes were associated with induction of an immunotherapeutic effect.

"I look forward. I feel insecure but I am ok with it". The experience of young HIV+ people attending transition preparation events: a qualitative investigation.

Transition programmes which prepare young people with HIV to manage the medical, social and psychological consequences of the condition can provide clinical benefits for both young people and their families. The London-based Looking Forward Project (LFP) is embedded within a National Health Service HIV family clinic. The project uses a group work approach and aims to equip HIV+ young people over the age of 12 years who know their status with the emotional, psychological and behavioural skills necessary to face the challenges of living with HIV. This small scale qualitative study investigated the experience of attendance, explored factors which facilitated participation in the groups and investigated the impact on their lives as a result of participation. Participants reported that the LFP events were educational but different to school-like activities, being with other young people reduced isolation and that receiving a voucher was an incentive to attend. Participation was facilitated through family support. Attendance at the LFP facilitated a positive attitude towards medication and hope for the future.

HIV+ children and their families in the UK: results from a family-clinic based 'look-back' exercise in London.

Advances in antiretroviral treatment have resulted in a growing number of HIV+ children surviving into adolescence and adulthood. However, HIV remains a chronic condition compounded by additional psychosocial stressors associated with living with HIV. The gold standard for treatment of HIV+ children and young people is within a family context. This 'look-back' exercise was conducted within an HIV family clinic context in London. HIV+ children's clinical notes were examined with the aim of describing the medical and social context of the families attending the clinic. Results showed that families are living with many psychosocial challenges that may have an impact on their ability to respond effectively to the challenge of living with HIV disease.