Pemetrexed plus platinum with or without pembrolizumab in patients with previously untreated metastatic nonsquamous NSCLC: protocol-specified final analysis from KEYNOTE-189.

BACKGROUND: In the phase III KEYNOTE-189 study (NCT02578680), pembrolizumab plus pemetrexed and platinum-based chemotherapy (pemetrexed-platinum) significantly improved overall survival (OS) and progression-free survival (PFS) in patients with previously untreated metastatic nonsquamous non-small-cell lung cancer (NSCLC) versus placebo plus pemetrexed-platinum. We report updated efficacy outcomes from the protocol-specified final analysis, including outcomes in patients who crossed over to pembrolizumab from pemetrexed-platinum and in patients who completed 35 cycles (∼2 years) of pembrolizumab. PATIENTS AND METHODS: Eligible patients were randomized 2 : 1 to receive pembrolizumab 200 mg (n = 410) or placebo (n = 206) every 3 weeks (for up to 35 cycles, ∼2 years) plus four cycles of pemetrexed (500 mg/m2) and investigators' choice of cisplatin (75 mg/m2) or carboplatin (area under the curve 5 mg·min/ml) every 3 weeks, followed by pemetrexed until progression. Patients assigned to placebo plus pemetrexed-platinum could cross over to pembrolizumab upon progression if eligibility criteria were met. The primary endpoints were OS and PFS. RESULTS: After a median follow-up of 31.0 months, pembrolizumab plus pemetrexed-platinum continued to improve OS [hazard ratio (HR), 0.56; 95% confidence interval (CI), 0.46-0.69] and PFS (HR, 0.49; 95% CI, 0.41-0.59) over placebo plus pemetrexed-platinum regardless of programmed death-ligand 1 expression. Objective response rate (ORR) (48.3% versus 19.9%) and time to second/subsequent tumor progression on next-line treatment (PFS2; HR, 0.50; 95% CI, 0.41-0.61) were improved in patients who received pembrolizumab plus pemetrexed-platinum. Eighty-four patients (40.8%) from the placebo plus pemetrexed-platinum group crossed over to pembrolizumab on-study. Grade 3-5 adverse events occurred in 72.1% of patients receiving pembrolizumab plus pemetrexed-platinum and 66.8% of patients receiving placebo plus pemetrexed-platinum. Fifty-six patients completed 35 cycles (∼2 years) of pembrolizumab; ORR was 85.7% and 53 (94.6%) were alive at data cut-off. CONCLUSIONS: Pembrolizumab plus pemetrexed-platinum continued to show improved efficacy outcomes compared with placebo plus pemetrexed-platinum, with manageable toxicity. These findings support first-line pembrolizumab plus pemetrexed-platinum in patients with previously untreated metastatic nonsquamous NSCLC.

[Evaluation of pulmonary lesions with positron emission tomography]. / Beurteilung von pulmonalen Herden mit der Positronenemissionstomographie.

Positron emission tomography (PET) with fluor-18-labeled deoxyglucose (FDG) enables metabolically oriented imaging of intrapulmonary lesions. PET is currently not used for the detection of lung metastases, but for further diagnostic differentiation of nodules that have already been detected. The diagnostic accuracy of FDG-PET is currently dependent on the size of the metastatic lesions and the uptake intensity. Significantly increased FDG uptake is strongly suggestive of malignant disease whatever the size of lesion concerned. Differentiation of a solitary metastasis from a primary lung tumor is not possible. Slightly elevated FDG uptake can also be found in tuberculosis, sarcoidosis and other granulomatous or inflammatory processes. Exclusion of metastatic disease with PET is currently only reliably possible for lesions larger than 2.0 cm in diameter, owing to respiratory motion and effects of partial volume.

[MR tomography of lung metastases with rapid gradient echo sequences. Initial results in diagnostic applications]. / MR-Tomographie von Lungenmetastasen mit schnellen Gradientenechosequenzen. Erste Ergebnisse in der diagnostischen Anwendung.

Rapid gradient echo sequences enable MR imaging (MRI) of pulmonary metastases with acquisition times of less than 1 s per slice. By optimization of this technique, density, T1- and T2-weighted images can be obtained (FLASH: TR 6.5 ms, TE2 = 3 ms, alpha = 10 degrees; T1w-Turbo-FLASH: TI 200 ms, TR 6.5 ms, TE2 = 3 ms, alpha = 10 degrees; T2w-Turbo-FLASH: TE1 = 50 ms, TR = 6.5 ms, TE2 = 3.5 ms; alpha = 10 degrees). In a prospective study 25 patients in whom pulmonary metastases were suspected were examined with three techniques in all three anatomical planes prior to surgery. All lung metastases revealed a high signal intensity on the FLASH as well as the T2w-Turbo-FLASH images, whereas vascular structures revealed a low signal intensity on the T2-weighted Turbo-FLASH images. Analysis regarding detection and correct number of lung metastases per patient with MRI compared with the histology revealed (n = 25): sensitivity of 82%, specificity 67%, positive predictive value of 95% and negative predictive value of 33%. While MRI does not currently have any diagnostic advantages over CT, the excellent differentiation of parenchymal lesions and vascular structures without the use of contrast medium and the variability of imaging planes are significant methodological advantages.

[Bilateral giant distended cysts in lymphangioleiomyomatosis of the lung as a rare cause of inflow obstruction]. / Beidseitige Riesenblähzysten bei Lymphangioleiomyomatose der Lunge als seltene Ursache einer Einflussstauung.

We report on a 27-year-old female developing acute thoracic inlet obstruction by bilateral pulmonary cysts which arose from pulmonary lymphangioleiomyomatosis and increased with respiratory treatment. Bilateral synchronous bullectomy via median sternotomy was necessary to resolve the life-threatening condition. The most frequent differential diagnoses are tension pneumothorax and pericardial tamponade. Although this case of thoracic inlet obstruction was caused by a rare disease it may serve to recall the therapeutic problems encountered in bullous pulmonary lesions under tension, especially regarding acute volume expansion due to one-way valve mechanism during respiratory treatment or general anaesthesia.