Immune-related adverse events predict the therapeutic efficacy of anti-PD-1 antibodies in cancer patients.

BACKGROUND: Cancer immune therapy has shown remarkable benefit in the treatment of a range of cancer types, although it may initiate autoimmune-related disorders in some patients. We have attempted to establish whether the incidence of irAEs after the use of anti-PD-1 antibodies nivolumab or pembrolizumab in advanced malignancies is associated with anti-PD-1 treatment efficacy. PATIENTS AND METHODS: We studied patients treated with single-agent nivolumab or pembrolizumab for advanced cancer. irAEs (immune-related adverse events) were identified clinically and graded as per the Common Terminology Criteria for Adverse Events version 4.0. Efficacy was evaluated with objective response rate (ORR, immune-Response Evaluation Criteria in Solid Tumours [RECIST] criteria) progression-free survival (PFS) and overall survival (OS). Tests were performed to determine the association between irAEs and ORR, PFS or OS. RESULTS: We identified 106 patients. Primary diagnoses were lung cancer (n = 77), melanoma (n = 8), head and neck carcinoma (n = 7), renal carcinoma (n = 5), Hodgkin's lymphoma (n = 3), urothelial carcinoma (n = 3) and gallbladder adenocarcinoma, hepatocellular carcinoma and Merkel cell carcinoma (n = 1 each). IrAEs were observed in 40 patients (37.7%). The most frequent irAEs were hypothyroidism (n = 15), nephritis (n = 5) and hyperthyroidism (n = 4). Objective response was observed in 44 patients (41.5%), and median PFS was 5.5 months (0.5-31 months). Thirty-three of the 40 patients with irAEs had objective response (82.5%) in contrast with 11 of the 66 cases without irAEs (16.6%) (OR 23.5, P < 0.000001). PFS in patients with irAEs was 10 months and 3 months in those without irAEs (HR 2.2, P = 0.016). OS in patients with irAEs was 32 months and 22 in those without irAEs, without statistically significant differences. CONCLUSION: In advanced cancer treated with single-agent anti-PD-1 antibodies, patients with irAEs showed a markedly improved efficacy over patients without irAEs (ORR of 82.5% and PFS of 10 months vs ORR of 16.6% and PFS of 3 months). Future studies of anti-PD-1 immune-therapy should address this association to explore the underlying biological mechanisms of efficacy.

Use of bevacizumab as a first-line treatment for metastatic breast cancer.

OBJECTIVE: During clinical practice, it can be challenging, given the lack of response biomarkers, to identify the patients with metastatic breast cancer (mbca) who would benefit most from the addition of bevacizumab to first-line standard chemotherapy. The aim of the present review was to summarize the relevant scientific evidence and to discuss the experience of a group of experts in using bevacizumab to treat mbca. METHODS: A panel of 17 Spanish oncology experts met to discuss the literature and their experience in the use of bevacizumab as first-line treatment for mbca. During the meeting, discussions focused on three main issues: the profile of the patients who could benefit most from bevacizumab, the optimal bevacizumab treatment duration, and the safety profile of bevacizumab. RESULTS: The subset of mbca patients who would benefit the most from the addition of bevacizumab to first-line standard chemotherapy are those with clinically defined aggressive disease. Treatment with bevacizumab should be maintained until disease progression or the appearance of unacceptable toxicity. In the mbca setting, the toxicity profile of bevacizumab is well known and can be managed in clinical practice after adequate training. CONCLUSIONS: This expert group recommends administering bevacizumab as first-line treatment in patients with clinically aggressive disease.

Unknown primary cancer of the head and neck: a multidisciplinary approach

The management of patients with cervical lymph node metastases from an unknown primary cancer (CUP) remains a matter of controversy. Although new advanced diagnostic tools, such as positron emission tomography, have recently been introduced in oncology, the frequency of this tumour entity in clinical practice means it is still relevant. Recently introduced molecular profiling platforms may provide biological classification for the primary tissue of origin as well as insights into the pathophysiology of this clinical entity, including the characterisation of the Epstein-Barr virus and human papilloma virus genomas in the metastatic cervical nodes. Due to the lack of randomised trials, a standard therapy has not been identified yet. Although neck dissection followed by post-operative radiotherapy is the most generally accepted approach, there are other curative options that can be used in some patients: neck dissection alone, nodal excision followed by post-operative radiotherapy or radiotherapy alone. A major controversy remains in the target radiation volumes that range from ipsilateral neck irradiation to prophylactic irradiation of all potential mucosal sites and both sides of the neck. Finally, the administration of concurrent chemotherapy is currently being advised for patients with adverse prognostic factors (AU)

Primary lingual abscess presenting as acute swelling of the tongue obstructing the upper airway: diagnosis with MR.

We report the sudden development of an inflammatory process thought to be of the floor of the mouth with subsequent involvement of the respiratory airway. MR imaging showed an enhancing posterior lingual lesion, consistent with an abscess. Immediate surgical drainage relieved the symptoms. MR imaging allowed accurate diagnosis, which was essential for surgical planning in a condition that was otherwise difficult to diagnose.