Neoadjuvant Nivolumab plus Chemotherapy in Resectable Lung Cancer.

BACKGROUND: Neoadjuvant or adjuvant chemotherapy confers a modest benefit over surgery alone for resectable non-small-cell lung cancer (NSCLC). In early-phase trials, nivolumab-based neoadjuvant regimens have shown promising clinical activity; however, data from phase 3 trials are needed to confirm these findings. METHODS: In this open-label, phase 3 trial, we randomly assigned patients with stage IB to IIIA resectable NSCLC to receive nivolumab plus platinum-based chemotherapy or platinum-based chemotherapy alone, followed by resection. The primary end points were event-free survival and pathological complete response (0% viable tumor in resected lung and lymph nodes), both evaluated by blinded independent review. Overall survival was a key secondary end point. Safety was assessed in all treated patients. RESULTS: The median event-free survival was 31.6 months (95% confidence interval [CI], 30.2 to not reached) with nivolumab plus chemotherapy and 20.8 months (95% CI, 14.0 to 26.7) with chemotherapy alone (hazard ratio for disease progression, disease recurrence, or death, 0.63; 97.38% CI, 0.43 to 0.91; P = 0.005). The percentage of patients with a pathological complete response was 24.0% (95% CI, 18.0 to 31.0) and 2.2% (95% CI, 0.6 to 5.6), respectively (odds ratio, 13.94; 99% CI, 3.49 to 55.75; P<0.001). Results for event-free survival and pathological complete response across most subgroups favored nivolumab plus chemotherapy over chemotherapy alone. At the first prespecified interim analysis, the hazard ratio for death was 0.57 (99.67% CI, 0.30 to 1.07) and did not meet the criterion for significance. Of the patients who underwent randomization, 83.2% of those in the nivolumab-plus-chemotherapy group and 75.4% of those in the chemotherapy-alone group underwent surgery. Grade 3 or 4 treatment-related adverse events occurred in 33.5% of the patients in the nivolumab-plus-chemotherapy group and in 36.9% of those in the chemotherapy-alone group. CONCLUSIONS: In patients with resectable NSCLC, neoadjuvant nivolumab plus chemotherapy resulted in significantly longer event-free survival and a higher percentage of patients with a pathological complete response than chemotherapy alone. The addition of nivolumab to neoadjuvant chemotherapy did not increase the incidence of adverse events or impede the feasibility of surgery. (Funded by Bristol Myers Squibb; CheckMate 816 ClinicalTrials.gov number, NCT02998528.).

Identifying the Steps Required to Effectively Implement Next-Generation Sequencing in Oncology at a National Level in Europe.

Next-generation sequencing (NGS) may enable more focused and highly personalized cancer treatment, with the National Comprehensive Cancer Network and European Society for Medical Oncology guidelines now recommending NGS for daily clinical practice for several tumor types. However, NGS implementation, and therefore patient access, varies across Europe; a multi-stakeholder collaboration is needed to establish the conditions required to improve this discrepancy. In that regard, we set up European Alliance for Personalised Medicine (EAPM)-led expert panels during the first half of 2021, including key stakeholders from across 10 European countries covering medical, economic, patient, industry, and governmental expertise. We describe the outcomes of these panels in order to define and explore the necessary conditions for NGS implementation into routine clinical care to enable patient access, identify specific challenges in achieving them, and make short- and long-term recommendations. The main challenges identified relate to the demand for NGS tests (governance, clinical standardization, and awareness and education) and supply of tests (equitable reimbursement, infrastructure for conducting and validating tests, and testing access driven by evidence generation). Recommendations made to resolve each of these challenges should aid multi-stakeholder collaboration between national and European initiatives, to complement, support, and mutually reinforce efforts to improve patient care.

The impact on the multidisciplinary team of molecular profiling for personalized therapy in non-small cell lung cancer.

The composition of the multidisciplinary team (MDT) that treats lung cancer varies by region and practice setting but generally includes a thoracic medical oncologist, a thoracic surgeon, a thoracic radiation oncologist, and an interventional radiologist, as well as a pathologist, pulmonologist, and specialist nurses. Growing clinical evidence supports a personalized approach to non-small cell lung cancer (NSCLC) treatment, and clinical trials in advanced disease have shown the value of testing for epidermal growth factor receptor gene (EGFR) mutations prior to first-line therapy with erlotinib or gefitinib and testing for anaplastic lymphoma kinase gene (ALK) rearrangements prior to therapy with crizotinib. The most recent National Comprehensive Cancer Network (NCCN) guidelines also recommend sequential EGFR and ALK testing for patients with a diagnosis of recurrent or metastatic adenocarcinoma, large cell carcinoma, or not otherwise specified histology, and simultaneous molecular screening has also been proposed. Here, we explore potential challenges for the MDT implied by the move toward personalized therapy in NSCLC and the increasing need for molecular diagnoses, and anticipate how the working roles and responsibilities of team members may develop to accommodate them.

Mycobacterium microti infection associated with spindle cell pseudotumour and hypercalcaemia: a possible link with an infected alpaca.

A 44-year-old woman who had recently been on immunosuppressive therapy presented with malaise, cough, fever, weight loss, lymphadenopathy, severe hypercalcaemia and a paratracheal mass on imaging. The initial impression was of disseminated malignancy, and lymphoma was suspected. A mediastinal biopsy showed a mycobacterial spindle cell pseudotumour containing acid and alcohol fast bacilli (AAFB). Sputum microscopy demonstrated AAFBs, confirmed as Mycobacterium tuberculosis complex by PCR. Prolonged culture grew Mycobacterium microti, an organism often associated with disease in small rodents and llamas. M microti isolates from postmortem samples of an alpaca at a nearby farm were genetically indistinguishable. Although the patient had not visited the farm, concurrent illness in her adopted stray cat suggested a possible zoonotic connection. The patient responded to antituberculous therapy, and rehydration and pamidronate for hypercalcaemia. We believe the hypercalcaemia was caused by a similar mechanism to raised calcium levels sometimes seen in tuberculosis.