In addition to prospective trials for non-small-cell lung cancers (NSCLCs) that are driven by less common genomic alterations, registries provide complementary information on patient response to targeted therapies. Here, we present the results of an international registry of patients with RETrearranged NSCLCs, providing the largest data set, to our knowledge, on outcomes of RET-directed therapy thus far. MethodsA global, multicenter network of thoracic oncologists identified patients with pathologically confirmed NSCLC that harbored a RET rearrangement. Molecular profiling was performed locally by reverse transcriptase polymerase chain reaction, fluorescence in situ hybridization, or nextgeneration sequencing. Anonymized data-clinical, pathologic, and molecular features-were collected centrally and analyzed by an independent statistician. Best response to RET tyrosine kinase inhibition administered outside of a clinical trial was determined by RECIST v1.1. ResultsBy April 2016, 165 patients with RET-rearranged NSCLC from 29 centers across Europe, Asia, and the United States were accrued. Median age was 61 years (range, 29 to 89 years). The majority of patients were never smokers (63%) with lung adenocarcinomas (98%) and advanced disease (91%). The most frequent rearrangement was KIF5B-RET (72%). Of those patients, 53 received one or more RET tyrosine kinase inhibitors in sequence: cabozantinib (21 patients), vandetanib (11 patients), sunitinib (10 patients), sorafenib (two patients), alectinib (two patients), lenvatinib (two patients), nintedanib (two patients), ponatinib (two patients), and regorafenib (one patient). The rate of any complete or partial response to cabozantinib, vandetanib, and sunitinib was 37%, 18%, and 22%, respectively. Further responses were observed with lenvantinib and nintedanib. Median progression-free survival was 2.3 months (95% CI, 1.6 to 5.0 months), and median overall survival was 6.8 months (95% CI, 3.9 to 14.3 months). ConclusionAvailable multikinase inhibitors had limited activity in patients with RET-rearranged NSCLC in this retrospective study. Further investigation of the biology of RET-rearranged lung cancers and identification of new targeted therapeutics will be required to improve outcomes for these patients.

PURPOSE For patients with resectable stage IIIA(N2) non–small-cell lung cancer, neoadjuvant chemotherapy with cisplatin and docetaxel followed by surgery resulted in a 1-year event-free survival (EFS) rate of 48% in the SAKK 16/00 trial and is an accepted standard of care. We investigated the additional benefit of perioperative treatment with durvalumab. METHODS Neoadjuvant treatment consisted of three cycles of cisplatin 100 mg/m2 and docetaxel 85 mg/m2 once every 3 weeks followed by two doses of durvalumab 750 mg once every 2 weeks. Durvalumab was continued for 1 year after surgery. The primary end point was 1-year EFS. The hypothesis for statistical considerations was an improvement of 1-year EFS from 48% to 65%. RESULTS Sixty-eight patients were enrolled, 67 were included in the full analysis set. Radiographic response rate was 43% (95% CI, 31 to 56) after neoadjuvant chemotherapy and 58% (95% CI, 45 to 71) after sequential neoadjuvant immunotherapy. Fifty-five patients were resected, of which 34 (62%) achieved a major pathologic response (MPR; ≤ 10% viable tumor cells) and 10 (18%) among them a complete pathologic response. Postoperative nodal downstaging (ypN0-1) was observed in 37 patients (67%). Fifty-one (93%) resected patients had an R0 resection. There was no significant effect of pretreatment PD-L1 expression on MPR or nodal downstaging. The 1-year EFS rate was 73% (two-sided 90% CI, 63 to 82). Median EFS and overall survival were not reached after 28.6 months of median follow-up. Fifty-nine (88%) patients had an adverse event grade ≥ 3 including two fatal adverse events that were judged not to be treatment-related. CONCLUSION The addition of perioperative durvalumab to neoadjuvant chemotherapy in patients with stage IIIA(N2) non–small-cell lung cancer is safe and exceeds historical data of chemotherapy alone with a high MPR and an encouraging 1-year EFS rate of 73%.

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These real-world data demonstrate similar response rates but inferior survival compared with those in early-phase trials. High PD-L1 expression and nonepitheloid histological subtype were associated with greater activity. Anti-PD-L1 immunotherapy is a reasonable second-line therapy in patients with MPM.

De novo concurrent ALK/KRAS co-alterations were associated with resistance to ALK TKI treatment in seven out of eight patients. In patients with ALK/EGFR co-alterations, outcomes with ALK and EGFR TKIs seem inferior to what would be expected in patients with either alteration alone, but further studies are needed to clarify which patients with ALK/EGFR co-alterations may still benefit from the respective TKI.

Background: Molecular imaging methods are currently used in the management of patients with lung cancer. Compared to non-small cell lung cancer, less data are available about the impact of molecular imaging using fluorine-18-fluorodeoxyglucose positron emission tomography/computed tomography (18 F-FDG PET/CT) in staging patients with small cell lung cancer (SCLC). Performing a systematic review and meta-analysis, we aimed to provide quantitative data about the impact of 18 F-FDG PET/CT in staging SCLC. Methods: A comprehensive literature search of studies on the use of 18 F-FDG PET/CT in patients with SCLC was performed. Three different databases were screened (PubMed/MEDLINE, EMBASE, and Cochrane library databases) until June 2019. Only articles describing the impact of 18 F-FDG PET/CT in staging patients with SCLC were selected. A pooled analysis evaluating the change of binary SCLC staging (limited-stage vs. extensive-stage disease) using 18 F-FDG PET/CT was carried out. Results: Nine articles including 721 patients with SCLC were included in the systematic review. Compared to conventional staging, a superior diagnostic accuracy of 18 F-FDG PET/CT was found. A change of binary SCLC staging using 18 F-FDG PET/CT was demonstrated in 15% (95% confidence interval, 9-21%) of patients with SCLC. Currently, it is not clearly demonstrated that the use of 18 F-FDG PET/CT for staging may improve the survival outcome of patients with SCLC. Conclusions: 18 F-FDG PET/CT is a useful molecular imaging method for staging patients with SCLC because it can change the management in a significant number of patients. More large prospective studies and cost-effectiveness analyses on the impact of 18 F-FDG PET/CT in staging patients with SCLC are needed.

Background: Systemic second-and third-line therapies for malignant pleural mesothelioma (MPM) result in a median progression-free survival (mPFS) of <2 months and median overall survival (mOS) of 6e9 months. Lurbinectedin binds to the DNA of the regulatory region while inhibiting tumour-associated macrophage transcription. In early trials, encouraging outcomes occurred in patients (pts) with MPM treated with lurbinectedin. We aimed to generate lurbinectedin efficacy and safety data among pts with progressive MPM. Patients and methods: Pts with progressing MPM treated with first-line platinum-pemetrexed chemotherapy with or without immunotherapy received lurbinectedin monotherapy. Treatment was given intravenously at 3.2 mg/m 2 dose every 3 weeks until progression or unacceptable toxicity. Using Simon's two-stage design, the primary endpoint, progression-free survival (PFS) at 12 weeks (PFS 12wks ), was met if achieved by !21 pts (p0 35% versus p1 !55%). Results: Forty-two pts from nine centres across Switzerland and Italy were recruited. Histology was epithelioid in 33 cases, sarcomatoid in 5, and biphasic in 4. Overall 10/42 (23.8%) underwent prior immunotherapy and 14/42 (33.3%) had progressed 6 months after first-line chemotherapy. At data cut-off PFS 12wks was met by 22/42 pts (52.4%; 90% confidence interval (CI): 38.7% to 63.5%; P ¼ 0.015) with an mPFS of 4.1 months and mOS of 11.1 months. The best response was complete and partial remission observed in one patient each and stable disease in 20 pts. The duration of disease control was 6.6 months (95% CI: 5.2e7.4). No significant difference in PFS 12wks, mPFS, and mOS was recorded in epithelioid versus non-epithelioid cases and pts with prior immunotherapy versus those without. Similar mPFS but shorter mOS were observed among pts who progressed within 6 months after first-line chemotherapy. Lurbinectedin-related grade 3e4 toxicity was seen in 21 pts, mostly being neutropenia (23.8%) and fatigue (16.7%). Conclusions: The primary efficacy endpoint was reached with acceptable toxicity. Lurbinectedin showed promising activity regardless of histology, prior immunotherapy, or outcome on prior treatment. ClinicalTrials.gov Identifier: NCT03213301

9016 Background: For patients (pts) with resectable stage IIIA(N2) non-small cell lung cancer (NSCLC) neoadjuvant chemotherapy (chemo) with 3 cycles cisplatin (cis)/docetaxel (doc) followed by surgery is an accepted standard of care leading to a 1-year (yr) event-free survival (EFS) of 48% and a 5-yr overall survival (OS) of 37%. PD-1/PD-L1 inhibitors have recently shown to lead to high response rates in resectable NSCLC. Methods: SAKK 16/14 is an open-label single-arm phase II study including 68 pts with resectable NSCLC stage IIIA(N2) (T1-3 N2 M0), irrespective of histological subtype, genomic aberrations or PD-L1 expression status. Neoadjuvant treatment consisted of 3 cycles of cis 100 mg/m2 and doc 85 mg/m2 q3w followed by 2 cycles of durvalumab 750 mg q2w. Durvalumab was continued after surgery q2w for 1 yr. The primary endpoint is EFS at 1 yr. The statistical hypothesis is to improve EFS at 1 yr from 48% based on the SAKK 16/00 study to 65%. Here, we report the primary endpoint and response data from 67 evaluable pts included in the study. Results: 68 pts were included from 06/16 to 01/19 and 67 pts (35 males, 32 females) were evaluable. Median age was 61 yrs (range, 41-74). 52 pts (77.6%) had a WHO PS of 0. 95.5% were current or former smokers. The majority of tumors were adenocarcinoma (55.2%) followed by squamous cell histology (32.8%). Clinical stage T1, T2 and T3 were present at diagnosis in 22.4%, 49.3% and 28.4%, respectively. 81.1% of pts underwent resection. The main reason for not undergoing surgery was disease progression (33.3%). Pneumonectomy was performed in 5 pts (9.1%), 43 pts underwent lobectomy and 7 pts bilobectomy. 30-day postoperative mortality was observed in one patient (1.8%). One patient died due to a bleeding complication after surgery most likely not related to neoadjuvant therapy. Radiographic response was 44.8% (95%CI: 32.6-57.4) after neoadjuvant chemo and 59.7% (95%CI: 46.4-71.9) after additional neoadjuvant immunotherapy. 1-yr EFS was 73.3% (90%CI: 62.5-81.4). Results for pathologic remission rate as well as correlation with PD-L1 status will be presented during the meeting. Conclusions: We report on treatment outcomes of the largest cohort of pts with resectable stage IIIA(N2) NSCLC receiving perioperative immune checkpoint inhibitor therapy. The addition of perioperative durvalumab to standard of care cis/doc is safe and leads to a high response rate and a very encouraging 1-yr EFS rate that appears substantially higher than with chemo alone. Clinical trial information: NCT 02572843.