Assessment of nivolumab in HIV-Infected patients with advanced non-small cell lung cancer after prior chemotherapy. The IFCT-1602 CHIVA2 phase 2 clinical trial.

IMPORTANCE: Therapies targeting immune checkpoints, such as the programmed cell death 1 (PD-1) receptor, have become the standard-of-care for patients with non-small cell lung cancer (NSCLC), but people living with HIV (PLWH) were excluded from these studies. OBJECTIVE: To evaluate the efficacy and tolerability of nivolumab in PLWH with advanced NSCLC. DESIGN: The CHIVA2 study was a nonrandomized, open-label, phase 2 clinical trial in PLWH with previously treated advanced NSCLC. SETTING: National multicenter prospective study. PARTICIPANTS: patients had viral load of <200 copies/mL, regardless of their CD4+ T-cell count. INTERVENTION: Nivolumab was administered in second or third line, as monotherapy intravenously at 3 mg/kg every 2 weeks, until disease progression or limiting toxicity. MAIN OUTCOMES AND MEASURES: The primary endpoint was disease control rate, evaluated using the Response Evaluation Criteria in Solid Tumors, version 1.1. Adverse events were graded using the National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0. RESULTS: Sixteen patients with advanced NSCLC were enrolled: 14 (88 %) were men, median age was 58 years (range: 44-71), and all were smokers. The median duration of nivolumab treatment was 3.5 months (range: 0.5-26.5). The median follow-up was 23.6 months. Disease control rate was 62.5 % for 15 evaluable patients at 8 weeks (2 with partial response, 8 with stable disease, and 5 with disease progression). Twelve (75 %) patients had treatment-related adverse events, which were mild or moderate, except for one patient experiencing severe pruritus, onycholysis, and pemphigoid. There were no opportunistic infections or unexpected immune-related events. HIV viral load was stable during treatment. An increase in proliferating CD8+ and CD4+ T-cells was observed after 3 nivolumab cycles in a subgroup of 9 patients. CONCLUSIONS AND RELEVANCE: Second/third-line nivolumab treatment was well-tolerated and beneficial in PLWH with NSCLC. Future trials should investigate immune checkpoint inhibitors in first-line settings. TRIAL REGISTRATION: EudraCT.ema.europa.eu registration number: 2016-003796-22.

Lung cancer in combined pulmonary fibrosis and emphysema: a series of 47 Western patients.

INTRODUCTION: The syndrome of combined pulmonary fibrosis and emphysema (CPFE) is characterized by imaging features consisting of the association of centrilobular and/or paraseptal emphysema and pulmonary fibrosis. Virtually all patients are smokers and thus at high risk of developing lung cancer. METHODS: This retrospective multicentre study was conducted by the Groupe d'Etudes et de Recherche sur les Maladies "Orphelines" Pulmonaires (GERM"O"P). RESULTS: A total of 47 patients presenting with lung cancer and CPFE syndrome were identified. All patients were smokers, with a mean of 47 pack-years. A pathological diagnosis of lung cancer was obtained for 38 (81%) patients. Histological type was squamous cell carcinoma in 17 (36%) patients, adenocarcinoma in 14 (30%), non-small-cell lung cancer not otherwise specified in three (6%), small-cell lung cancer in three (6%), and sarcomatoid carcinoma in one (2%). Overall, 20 of the 47 patients could not receive standard-of-care treatment for lung cancer, as per international recommendations or guidelines; this limitation was considered to be directly related to the CPFE syndrome in eight (40%) cases. CONCLUSION: Lung cancer in patients with CPFE syndrome represents a specific entity with a poor prognosis, that further represents the most characteristic and severe model of tobacco-related disease.

[Pulmonary hypertension in interstitial lung diseases: diagnostic and therapeutic approach in 2011?]. / Hypertension pulmonaire des fibroses pulmonaires: quelle approche diagnostique et thérapeutique en 2011?

Pulmonary hypertension is frequent in late-stage idiopathic pulmonary fibrosis, and is associated with a shorter survival. It should be suspected in case of dyspnea or hypoxemia disproportionate with the degree of parenchymal lung disease. It is particularly frequent in patients with the syndrome of combined pulmonary fibrosis and emphysema, and associated with a short survival (median survival less than 1 year). Pulmonary hypertension associated with chronic infiltrative lung diseases can be detected by echocardiography and must be confirmed by right-sided heart catheterization, especially to rule out post-capillary pulmonary hypertension frequent in this context. Management is mainly palliative and based on supplemental nasal oxygen. Therapy specific for pulmonary arterial hypertension, poorly evaluated in pulmonary hypertension associated with infiltrative lung diseases, is occasionally proposed to patients with disproportionate pulmonary hypertension (mean PAP > 35 mmHg), with often limited efficacy, and requiring careful follow-up (risk of increased hypoxemia) and invasive evaluation. Pulmonary transplantation should be considered in the absence of contra-indication.

Conditions associated with severe carbon monoxide diffusion coefficient reduction.

OBJECTIVE: To identify conditions associated with severe carbon monoxide transfer coefficient reduction (Kco < 40% of predicted values). PATIENTS AND METHODS: We retrospectively reviewed pulmonary function tests, such as Kco measurement, in consecutive patients evaluated in the physiology unit of a University hospital over a 6-year period. Patients were included if they had at least 1 measure of severe Kco reduction, with further detailed pulmonary function tests, clinical data, and diagnostic procedures conducted within 6 months. RESULTS: 5576 patients underwent 9061 Kco measurements. 195 patients (3.5%) with Kco < 40% were investigated (156 males; mean age 62 ± 12 years). Mean Kco was 29 ± 9% of predicted values. The main conditions associated with severe Kco reduction were: emphysema (46%); interstitial lung disease (28%); combined pulmonary fibrosis and emphysema (16%); and pre-capillary pulmonary hypertension (8%). Systolic pulmonary artery pressure was ≥ 35 mmHg at echocardiography in 88% of patients. Right heart catheterization performed in 97 patients showed pre-capillary pulmonary hypertension in 86 of 195 patients (44%). Pulmonary hypertension was the most frequent condition associated with Kco severe reduction. Pulmonary hypertension was present in 29%, 53%, and 48% of patients with chronic obstructive pulmonary disease, interstitial lung disease, and combined pulmonary fibrosis and emphysema, respectively, and was disproportionate to the parenchymal lung disease (mean pulmonary artery pressure > 35 mmHg) in 63% of cases. CONCLUSION: Severe Kco reduction is frequently related to pulmonary hypertension, especially when associated with emphysema and/or interstitial lung disease. Systematic echocardiography is thus warranted in any patient with severe Kco diminution.