Brigatinib for Pretreated, ALK-Positive, Advanced Non-Small-Cell Lung Cancers: Long-Term Follow-Up and Focus on Post-Brigatinib Lorlatinib Efficacy in the Multicenter, Real-World BrigALK2 Study.

Brigatinib is a next-generation ALK inhibitor (ALKi) that shows efficacy in ALK inhibitor naïve and post-crizotinib ALK+ advanced NSCLCs (aNSCLCs). The efficacy of brigatinib was retrospectively assessed in patients with aNSCLCs included in the brigatinib French Early-Access Program (1 August 2016−21 January 2019). The primary endpoint was investigator-assessed progression-free survival (invPFS) and the primary analysis was updated in 2021 with a longer follow-up, focused on post-brigatinib lorlatinib efficacy. Sixty-six centers included 183 patients: median age 60 ± 12.7 years; 78.3% never/former smokers; median of 3 ± 1 previous lines and 2 ± 0.5 ALKis; 37.1% ECOG PS 2 and 55.6% >3 metastatic sites. The median follow-up from brigatinib initiation was 40.4 months (95% CI 38.4−42.4). InvPFS was 7.4 months (95% CI 5.9−9.6), median duration of treatment (mDOT) was 7.3 months (95% CI 5.8−9.4) and median overall survival (mOS) was 20.3 months (95% CI 15.6−27.6). The median DOT and OS from brigatinib initiation tend to decrease with the number of ALK inhibitors used in previous lines of therapy. Based on the data collected, 92 (50.3%) patients received ≥1 agent(s) post-brigatinib and 68 (73.9%) of them received lorlatinib, with 51 (75%) immediately receiving it post-brigatinib, 12 (17.6%) receiving it after one and 5 (7.4%) after ≥2 subsequent treatments. The median follow-up was 29.9 (95% CI 25.7−33.1) months. Lorlatinib mDOT was 5.3 (95% CI 3.6−7.6) months with a median OS from lorlatinib initiation of 14.1 (95% CI 10.3−19.2) months. The results of the brigALK2 study confirm the efficacy of brigatinib in a population of heavily pretreated ALK+ aNSCLC patients and provide new data on the activity of lorlatinib after brigatinib.

Salvage Immunotherapy With Pembrolizumab in Patients Hospitalized for Life-Threatening Complications of NSCLC.

INTRODUCTION: It is not known whether patients with NSCLC who are hospitalized because of cancer-related complications are liable to benefit from salvage immunotherapy. METHODS: This is a multicenter observational study including five centers, which involve all patients with advanced-stage NSCLC exhibiting a level of programmed death-ligand 1 (PD-L1) greater than or equal to 1%, having been hospitalized because of complications attributed to the evolution of the NSCLC, and having started pembrolizumab treatment during their hospitalization because of a risk of clinical deterioration in the short term. The analysis measured overall survival (OS) and the rate of discharge to home at 3 months. RESULTS: The study included 33 patients, including 28 (85%) with metastatic NSCLC and 27 (82%) under first-line treatment. The main causes of hospitalization were deterioration of the general condition (52%), acute respiratory failure (18%), and an uncontrolled infection owing to the tumor (15%). A total of 20 patients (60%) had a performance status greater than or equal to 2 and 15 (45%) were under oxygen therapy. A total of 29 patients (88%) had a PD-L1 greater than or equal to 50%. Five patients (15%) started pembrolizumab in the intensive care unit. The median OS was 4.3 months (95% confidence interval [CI]: 0.9-not reached), and the 6-month and 1-year OS rates were 41.5% (95% CI: 27.5%-62.6%) and 32.6% (95% CI: 19.0%-55.9%), respectively. The home discharge rate at 3 months was 39% (95% CI: 23%-58%). CONCLUSIONS: Even when initiated in patients hospitalized for a life-threatening clinical deterioration, pembrolizumab seems to prolong the survival of certain patients with high PD-L1 NSCLC. Prospective, controlled data are necessary to confirm these results.

Intracerebral efficacy and tolerance of nivolumab in non-small-cell lung cancer patients with brain metastases.

OBJECTIVES: Although nivolumab has shown efficacy against non-small-cell lung cancers (NSCLCs), patients with active brain metastases (BMs) were excluded from pivotal clinical trials. Hence, data regarding nivolumab intracerebral activity and safety in NSCLC patients with BMs are scarce. MATERIALS AND METHODS: We conducted a retrospective multicenter study on NSCLC patients with BMs treated with nivolumab. The primary endpoint was intracerebral objective response rate (IORR), according to RECIST criteria. Secondary endpoints included intracerebral control rate, intracerebral and general progression-free survival (PFS), overall survival (OS) and tolerance. RESULTS AND CONCLUSION: Forty-three patients were included. BMs were locally pretreated in 34 (79%) patients and active in 16 (37%) patients. Median follow-up was 5.7 (95% CI: 2.7-8.4) months. IORR and extracerebral response rate were, respectively, 9% (95% CI: 3-23%) and 11% (95% CI: 4-26%). Intracerebral control rate was 51% (95% CI: 37-66%). Median intracerebral and general PFS lasted 3.9 (95% CI: 2.8-11.1) and 2.8 (95% CI: 1.8-4.6) months, respectively. Median OS was 7.5 (95% CI: 5.6-not reached) months. Five neurological adverse events occurred, including 1 grade-4 transient ischemic attack of uncertain imputability and 1 grade-3 neurological deficit; neither required nivolumab discontinuation. Nivolumab intracerebral activity was similar to its reported extracerebral efficacy, with an acceptable safety profile. Prospective and controlled data are needed to determine nivolumab's place in treatment of NSCLC patients with BMs.

Improvement of refractory rheumatoid arthritis-associated constrictive bronchiolitis with etanercept.

Rheumatoid arthritis (RA)-associated constrictive bronchiolitis is a severe condition with no established efficient treatment. A 55-year-old woman with seropositive RA developed rapidly progressive constrictive bronchiolitis confirmed by lung biopsy. Her clinical condition worsened despite steroids and azathioprine. Treatment with etanercept-a tumor necrosis factor (TNF)-alpha inhibitor-combined with methotrexate, resulted in a marked improvement of both her clinical condition and pulmonary function tests. Treatment with TNF-alpha inhibitors and methotrexate may be proposed in RA-associated constrictive bronchiolitis, a severe condition hitherto not amenable to improvement.