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Purpose: HER2 exon 20 insertions and point mutations are oncogenic drivers found in 1%-2% of patients with non-small-cell lung cancer (NSCLC). No targeted therapy is approved for this subset of patients. We prospectively evaluated the effectiveness of the combination of two antibodies against human epidermal growth factor 2 (HER2 [HER2] trastuzumab and pertuzumab with docetaxel; trastuzumab and pertuzumab) and docetaxel., Methods: The IFCT 1703-R2D2 trial is a multicenter, nonrandomized phase II study. Patients with HER2 -mutated, advanced NSCLC who progressed after ≥ 1 platinum-based treatment were enrolled. Patients received pertuzumab at a loading dose of 840 mg and 420 mg thereafter; trastuzumab at an 8 mg/kg loading dose and 6 mg/kg thereafter; and docetaxel at a dose of 75 mg/m 2 every 3 weeks. The primary outcome was the objective response rate (ORR). Other end points included the duration of response, progression-free survival, and safety (NCT03845270)., Results: Forty-five patients were enrolled and treated. The median age was 64.5 years (range, 31-84 years), 35% were smokers, 72% were females, 15% had an Eastern Cooperative Oncology Group performance status of 2, and 30% had brain metastases. The objective response rate was 29% (n = 13), and 58% had stable disease (n = 26). The median progression-free survival was 6.8 months (95% CI, 4.0 to 8.5). The median duration of response in patients with a confirmed response (n = 13) was 11 months (95% CI, 2.9 to 14.9). Grade 3/4 treatment-related adverse events were observed in 64% of the patients. No patient discontinued treatment because of toxicity. The most frequent grade ≥ 3 treatment-related adverse events were neutropenia (33%), diarrhea (13%), and anemia (9%)., Conclusion: Triple therapy with trastuzumab, pertuzumab, and docetaxel is feasible and effective for HER2 -mutated pretreated advanced NSCLC. These results highlight the effectiveness of the HER2 antibody-based strategy, which should be considered for these patients., Competing Interests: Julien MazieresConsulting or Advisory Role: Novartis, Roche/Genentech, Pfizer, Bristol Myers Squibb, Lilly/ImClone, MSD, AstraZeneca, Pierre Fabre, Blueprint Medicines, Hengrui TherapeuticsResearch Funding: Roche (Inst), Bristol Myers Squibb (Inst), AstraZeneca (Inst), Pierre Fabre (Inst)Travel, Accommodations, Expenses: Pfizer, Roche, Bristol Myers Squibb Charles RicordelConsulting or Advisory Role: BMS, AstraZeneca/MedImmune, Takeda Laurent GreillierHonoraria: AstraZeneca, Boehringer Ingelheim, Roche, Bristol Myers Squibb, MSD, Takeda, AbbVie, Novartis, PfizerConsulting or Advisory Role: Roche, Boehringer Ingelheim, Bristol Myers Squibb, Takeda, MSD, AstraZeneca, AbbVie, NovartisTravel, Accommodations, Expenses: Boehringer Ingelheim, Roche, MSD Gérard ZalcmanHonoraria: Roche, Lilly, Pfizer, Bristol Myers Squibb, AstraZeneca, Boehringer Ingelheim, MSD Oncology, Inventiva PharmaConsulting or Advisory Role: Roche (Inst), Boehringer Ingelheim (Inst), Pfizer (Inst), Bristol Myers Squibb (Inst), Boehringer Ingelheim (Inst), MSD Oncology (Inst), Inventiva Pharma (Inst), AstraZeneca (Inst), Da Volterra (Inst)Research Funding: Roche (Inst), Pfizer (Inst), AstraZeneca (Inst), Roche (Inst), Bristol Myers Squibb (Inst), Takeda (Inst)Travel, Accommodations, Expenses: Roche, Lilly, Pfizer, Bristol Myers Squibb, Pfizer, AstraZeneca, AbbVie Charlotte DomblidesHonoraria: AstraZeneca, BMSConsulting or Advisory Role: Amgen, AstraZenecaTravel, Accommodations, Expenses: Amgen, AstraZeneca, BMS, Pfizer, Roche Jeannick MadelaineTravel, Accommodations, Expenses: GlaxoSmithKline, AstraZeneca/Merck, Boehringer Ingelheim France, Novartis, Pfizer, MSD, Roche, Amgen, Bristol Myers Squibb, Takeda Jaafar BennounaHonoraria: Servier, AstraZeneca, MSD Oncology, Bristol Myers Squibb, Novartis, Amgen, DaichiiConsulting or Advisory Role: Roche, Bristol Myers Squibb, MSD, Servier, AstraZeneca, Novartis, AmgenResearch Funding: AstraZeneca (Inst)Travel, Accommodations, Expenses: Roche, AstraZeneca, Bristol Myers Squibb Céline MascauxHonoraria: Roche, Astrazeneca, Kephren, Bristol Myers Squibb, Pfizer, Sanofi, MSD, TakedaConsulting or Advisory Role: Roche, Sanofi, Takeda, Pfizer, Bristol Myers Squibb, MSD, AstraZeneca, Kephren, Amgen Denis Moro-SibilotConsulting or Advisory Role: Roche/Genentech, Boehringer Ingelheim, Lilly/ImClone, Sanofi, Novartis, Amgen, Pfizer, AstraZeneca, Clovis Oncology, MSD Oncology, ARIAD, Bristol Myers Squibb, Takeda, AbbVie, Becton DickinsonResearch Funding: AbbVie (Inst), Boehringer Ingelheim France (Inst), Roche/Genentech (Inst), Bristol Myers Squibb (Inst)Expert Testimony: MSD OncologyTravel, Accommodations, Expenses: Roche/Genentech, Lilly/ImClone, Pfizer, MSD Oncology, Bristol Myers Squibb François PinquieHonoraria: Roche, AstraZenecaConsulting or Advisory Role: AstraZenecaTravel, Accommodations, Expenses: Takeda, MSD Alexis B. CortotHonoraria: Takeda, Bristol Myers Squibb, AstraZeneca, Roche, Novartis, Pfizer, MSD OncologyConsulting or Advisory Role: AstraZeneca, Boehringer Ingelheim, Pfizer, Roche, Novartis, TakedaResearch Funding: Merck Serono (Inst), Novartis (Inst), Roche (Inst)Travel, Accommodations, Expenses: Roche, AstraZeneca, Pfizer, Novartis Jacques CadranelHonoraria: AstraZeneca/MedImmune, Bristol Myers Squibb, Roche/Genentech, Merck Sharp & Dohme, Boehringer IngelheimConsulting or Advisory Role: AstraZeneca/MedImmune, Roche/Genentech, Boehringer Ingelheim, Bristol Myers Squibb, Takeda, Merck Sharp & Dohme, Pfizer, Lilly, NovartisResearch Funding: Pfizer (Inst), Novartis (Inst), AstraZeneca/MedImmune (Inst) Virginie WesteelConsulting or Advisory Role: AstraZeneca, Bristol Myers Squibb, Takeda, MSD Oncology, RocheSpeakers' Bureau: Roche, AstraZeneca, Bristol Myers SquibbResearch Funding: Roche (Inst), Bristol Myers Squibb (Inst), MSD Oncology (Inst), Novartis (Inst), AbbVie (Inst), Boehringer Ingelheim (Inst), Lilly (Inst), Merck Serono (Inst)Travel, Accommodations, Expenses: Bristol Myers Squibb, AstraZeneca, MSD Oncology Benjamin BesseResearch Funding: AstraZeneca (Inst), Pfizer (Inst), Lilly (Inst), Onxeo (Inst), Bristol Myers Squibb (Inst), Inivata (Inst), AbbVie (Inst), Amgen (Inst), Blueprint Medicines (Inst), Celgene (Inst), GlaxoSmithKline (Inst), Sanofi (Inst), Takeda (Inst), Cristal Therapeutics (Inst), Daiichi Sankyo (Inst), Janssen Oncology (Inst), OSE Immunotherapeutics (Inst), BeiGene (Inst), Boehringer Ingelheim (Inst), Roche/Genentech (Inst), Tolero Pharmaceuticals (Inst), 4D Pharma (Inst), Aptitude Health (Inst), cergentis (Inst)No other potential conflicts of interest were reported.

Purpose: Double inhibition of epidermal growth factor receptor (EGFR) using a tyrosine kinase inhibitor plus a monoclonal antibody may be a novel treatment strategy for non-small cell lung cancer (NSCLC). We assessed the efficacy and toxicity of afatinib + cetuximab versus afatinib alone in the first-line treatment of advanced EGFR -mutant NSCLC., Patients and Methods: In this phase II, randomized, open-label study, patients with stage III/IV EGFR -positive NSCLC were randomly assigned (1:1) to receive afatinib (group A) or afatinib + cetuximab (group A + C). Oral afatinib 40 mg was given once daily; cetuximab 250 mg/m² was administered intravenously on day 15 of cycle 1, then every 2 weeks at 500 mg/m² for 6 months. The primary endpoint was time to treatment failure (TTF) rate at 9 months. Exploratory analysis of EGFR circulating tumor DNA in plasma was performed., Results: Between June 2016 and November 2018, 59 patients were included in group A and 58 in group A + C. The study was ended early after a futility analysis was performed. The percentage of patients without treatment failure at 9 months was similar for both groups (59.3% for group A vs. 64.9% for group A + C), and median TTF was 11.1 (95% CI, 8.5-14.1) and 12.9 (9.2-14.5) months, respectively. Other endpoints, including progression-free survival and overall survival, also showed no improvement with the combination versus afatinib alone. There was a slight numerical increase in grade ≥3 adverse events in group A + C. Allele frequency of the EGFR gene mutation in circulating tumor DNA at baseline was associated with shorter PFS, regardless of the treatment received., Conclusions: These results suggest that addition of cetuximab to afatinib does not warrant further investigation in treatment-naïve advanced EGFR -mutant NSCLC., (©2021 American Association for Cancer Research.)

Introduction TAS-114 is a potent inhibitor of deoxyuridine triphosphatase, which is a gatekeeper protein preventing uracil and 5-fluorouracil (5-FU) misincorporation into DNA. TAS-114 has been suggested to enhance the antitumor activity of 5-FU. This randomized, phase 2 study investigated TAS-114 plus S-1 (TAS-114/S-1) vs. S-1 in non-small-cell lung cancer (NSCLC) patients. Methods Patients with advanced NSCLC, previously treated with ≥ 2 regimens, were randomized 1:1 to receive TAS-114 (400 mg)/S-1 (30 mg/m 2 ) or S-1 (30 mg/m 2 ). Progression-free survival (PFS, independent central review) was the primary endpoint. Secondary endpoints included disease control rate (DCR), overall survival (OS), overall response rate (ORR), and safety. Results In total, 127 patients received treatment. Median PFS was 3.65 and 4.17 months in the TAS-114/S-1 and S-1 groups, respectively (hazard ratio [HR] 1.16, 95% confidence interval [CI] 0.71-1.88; P = 0.2744). DCR was similar between groups (TAS-114/S-1 80.3%, S-1 75.9%) and median OS was 7.92 and 9.82 months for the TAS-114/S-1 and S-1 groups, respectively (HR 1.31, 95% CI 0.80-2.14; P = 0.1431). The ORR was higher in the TAS-114/S-1 group than the S-1 group (19.7% vs. 10.3%), and more patients with tumor shrinkage were observed in the TAS-114/S-1 group. Incidence rates of anemia, skin toxicities, and Grade ≥ 3 treatment-related adverse events were higher in the TAS-114/S-1 group compared with the monotherapy group. Conclusions Although the TAS-114/S-1 combination improved the response rate, this did not translate into improvements in PFS. Clinical Trial Registration No. NCT02855125 (ClinicalTrials.gov) registered on 4 August 2016.

Purpose: The incidence of lung cancer has dramatically increased in women. Preclinical data have suggested that combining EGFR-tyrosine kinase inhibitor (TKI) with an antiestrogen may overcome resistance to EGFR-TKI., Patients and Methods: The IFCT-1003 LADIE trial was a 2 × 2 arms parallel open-label randomized phase II trial. EGFR-TKI-naïve postmenopausal women with advanced lung cancer were treated with gefitinib (G) versus gefitinib + fulvestrant (G+F) in the EGFR-mutated group (EGFR + ) or with erlotinib (E) versus erlotinib + fulvestrant (E+F) in the EGFR wild-type group (EGFR-WT). The primary objective was progression-free survival (PFS) at 3 and 9 months for EGFR-WT and EGFR + patients., Results: Overall, 204 patients (gefitinib 104 and G+F 100) and 175 patients (erlotinib 87 and E+F 88) were enrolled in the EGFR + and EGFR-WT cohorts. In the EGFR + cohort, the primary endpoint was reached, with 58% of the G+F group patients being nonprogressive at 9 months. Adding fulvestrant to gefitinib was not associated with improved PFS (9.9 vs 9.4 months) or overall survival (OS; 22.1 vs 28.6 months). In the EGFR-WT cohort, the primary endpoint was also achieved (33.7% of the patients were nonprogressive at 3 months). Adding fulvestrant to erlotinib was not associated with improved outcome (PFS 1.8 vs 2.0 and OS 10.3 vs 7.3 months). No PFS difference was observed regarding estrogen receptor alpha expression. The tolerance was as expected with no treatment-related death., Conclusions: Adding fulvestrant to EGFR-TKI is feasible, but not associated with prolonged PFS regardless of EGFR status. The lack of benefits while combining fulvestrant to EGFR-TKI does not support its future development in an unselected population., (©2020 American Association for Cancer Research.)

Purpose: Second-line chemotherapy regimens have demonstrated poor benefit after failure of platinum-based chemotherapy in advanced non-squamous non-small-cell lung cancer (nsNSCLC)., Methods: In this multicentre, open-label phase III trial, patients with advanced nsNSCLC treated with one or two prior lines, including one platinum-based doublet, were centrally randomised to receive 90 mg/m 2 of paclitaxel (D1, D8, D15) plus 10 mg/kg of bevacizumab (D1, D15) every 28 days or docetaxel (75 mg/m 2 ) every 21 days; crossover was allowed after disease progression. Primary end-point was progression-free survival (PFS). ClinicalTrials.gov registration number: NCT01763671., Results: One hundred sixty six patients were randomised (paclitaxel plus bevacizumab: 111, docetaxel: 55). The median PFS was longer in patients receiving paclitaxel plus bevacizumab than in patients receveing docetaxel [5·4 months versus 3·9 months, adjusted hazard ratio (HR) 0·61 (95% confidence interval [CI]: 0·44-0·86); p = 0·005]. Objective response rates (ORRs) were 22·5% (95% CI: 14·8-30·3) and 5·5% (95% CI: 0·0-11·5) (p = 0·006), respectively. Median overall survivals were similar (adjusted HR 1·17; p = 0·50). Crossover occurred in 21 of 55 (38·2%) docetaxel-treated patients. Grade III-IV adverse events (AEs) were reported in 45·9% and 54·5% of patients treated with paclitaxel and bevacizumab or docetaxel, respectively (p = NS), including neutropenia (19·3% versus 45·4%), neuropathy (8·3% versus 0·0%) and hypertension (7·3% versus 0·0%). Three patients died due to treatment-related AEs (1·8% in each group)., Conclusion: Weekly paclitaxel plus bevacizumab as second- or third-line improves PFS and ORR compared with docetaxel in patients with nsNSCLC, with an acceptable safety profile. These results place weekly paclitaxel plus bevacizumab as a valid option in this population., Clinical Trials Registration Number: ClinicalTrials.gov Identifier: NCT01763671., Competing Interests: Conflict of interest statement A.B.C. has reported receiveing honoraria from Roche, AstraZeneca, Bristol-Myers Squibb, BoehringerIngelheim, MSD, Novartis and Pfizer and travel grants from Roche, AstraZeneca, BoehringerIngelheim, Novartis and Pfizer. C.A.V. has reported receiving grants, personal fees and non-financial support from Roche. O.M. has received personal fees from BMS, BoehringerIngelheim, Astra Zeneca, Novartis and Hoffman-Roche. F.B. has received personal fees from Astra Zeneca, BMS, BoehringerIngelheim, Clovis Oncology, Eli Lilly Oncology, Hoffman-Roche, Novartis, Merck, MSD, Pierre Fabre and Pfizer. G.Z. has received grant from Roche and BMS, personal fees from Roche, BMS, Astra Zeneca and MSD and non-financial support from BMS, Astra Zeneca and Pfizer. D.P. has received personal fees from Roche Hoffman, Astellas, Lilly, Janssen, BMS, Merck, Astra Zeneca, Novartis, Sanofi and Pfizer. C.F.D. has received other support from MSD (CPLF 2017), Laidet Medical (ERS 2016) and BoehringerIngelheim (CPLF 2016). E.P. has received personal fees and non-financial support from Astra Zeneca and BMS and personal fees from Pfizer. D.M-.S. has received personal fees from Roche, BMS, MSD and Eli Lilly. B.B. has received institutional grants for clinical and translational research from AstraZeneca, BMS, Boehringer-Ingelheim, Lilly, Pfizer, Roche-Genentech, Sanofi-Aventis, Clovis, GSK, Servier, EOS, Onxeo, OncoMed, Inivata and OSE Pharma. All other authors have no conflict of interest to declare., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Objectives: Efficacy and safety of necitumumab when combined with pembrolizumab was assessed in patients with Stage IV non-small cell lung cancer (NSCLC) of squamous and nonsquamous histology, who had progressed after treatment with a platinum-based doublet., Materials and Methods: This single-arm, multicenter, phase Ib study had a dose-finding phase, in which escalating doses of necitumumab (600 mg and 800 mg IV) were administered on Day 1 and 8 every 3 weeks (Q3W) in combination with pembrolizumab (200 mg IV) on Day 1 Q3W, and expansion cohorts. Patients were treated until progressive disease (PD), toxicity requiring cessation, protocol noncompliance, or withdrawal of consent. Efficacy was evaluated by overall response rate (ORR)., Results: In 64 treated patients (32 patients [50 %] were programmed death-ligand 1 [PD-L1] negative), confirmed ORR was 23.4 % (95 % confidence interval [CI] 13.8 %-35.7 %). Two patients (3.1 %) had complete response (CR), 13 patients (20.3 %) had partial response (PR), 26 patients (40.6 %) had stable disease, 17 patients (26.6 %) had PD, and 6 patients (9.4 %) were not evaluable. Regardless of histology or PD-L1 status, median PFS (mPFS) was 4.1 months (95 % CI 2.4-6.9 months) and OS at 6 months was 74.7 % (61.5%-83.9%). Confirmed disease control rate was 64.1 % (95 % CI 51.5-75.7). Patients with programmed death-ligand 1 (PD-L1) ≥1% had numerically improved ORR and median progression-free survival when compared with patients with PD-L1 negative cancer. No dose-limiting toxicities were recorded and the combination of necitumumab 800 mg with pembrolizumab 200 mg was considered tolerable., Conclusion: Results suggest modest benefits of second-line necitumumab and pembrolizumab combination therapy in patients with Stage IV NSCLC. Safety profiles were consistent with class effects typical of epidermal growth factor receptor inhibitors and immunotherapies with no additive toxicities., Competing Interests: Declaration of Competing Interest BB has received research grants from Abbvie, Amgen, AstraZeneca, BeiGene, Blueprint Medicines, BMS, Boehringer Ingelheim, Celgene, Cristal Therapeutics, Daiichi-Sankyo, Eli Lilly, GSK, Ignyta, IPSEN, Inivata, Janssen, Merck KGaA, MSD, Nektar, Onxeo, OSE immunotherapeutics, Pfizer, Pharma Mar, Roche-Genentech, Sanofi, Servier, Spectrum Pharmaceuticals, Takeda, Tiziana Pharma, Tolero Pharmaceuticals. PG has provided consulting and advisory services for Roche, Merck Sharp & Dohme, Bristol-Myers Squibb, Boehringer Ingelheim, Pfizer, Abbvie, Guardant Health, Novartis, Eli Lilly and Company, Astra-Zeneca, Jansen, Sysmex, Blueprint Medicines, Takeda, and undertaken speaking and/or public presentations for Roche, Merck Sharp & Dohme, Bristol-Myers Squibb, Pfizer, Novartis, Boehringer Ingelheim, Rovi. ABC has received honoraria or consultation fees from AstraZeneca, Bristol Myers Squibb, Boehringer Ingelheim, Merck Sharp & Dohme, Novartis, Pfizer, and Roche, and has received research grants from Novartis and Merck HM has received personal fees from Chugai Pharma, AstraZeneca, Lilly Japan, Ono Pharmaceutical, Taiho Pharmaceutical, Bristol-Myers Squibb Japan, Merck Sharp & Dohme, Boehringer Ingelheim, Pfizer, and Novartis. MJ has provided consulting and advisory services for Genentech/Roche, Celgene, Boehringer Ingelheim, Sanofi, Mirati, LOXO, Calithera, AstraZeneca, Merck, Araxes Pharma, Mersana Therapeutics, BeiGene, Incyte, Pfizer, Guardant Health, Bristol Myers Squibb, Ribon Therapeutics. MG was an employee of Eli Lilly and Company at the time the study was conducted. AG has provided consulting services for Novartis; has received travel, accommodation, congress registration expenses from Boehringer Ingelheim, Novartis, Pfizer, Roche ; has received research grants from Astrazeneca, Bristol Myers Squibb, Boehringer Ingelheim, Janssen Cilag, Merck, Novartis, Pfizer, Roche, Sanofi. JB has received honoraria for participating in advisory boards for Roche, Boehringer-Ingelheim, MSD, Bristol-Myers Squibb, Astra-Zeneca, Servier; has received institutional grants from Astra-Zeneca; received honoraria for participating in symposia for Roche, Astra-Zeneca, Boehringer- Ingelheim, Bristol-Myers Squibb, Servier., (Copyright © 2020. Published by Elsevier B.V.)

Background: Anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors (TKIs) have shown efficacy in the treatment of ALK-rearranged non-small-cell lung cancer (NSCLC), but the disease eventually progresses in all patients. In many cases, resistance to ALK TKIs arises through ALK mutations. Although clinical and biological data suggest variations in TKI efficacy according to the mechanism of resistance, ALK mutations are still rarely investigated in routine practice., Materials and Methods: We performed a retrospective multicentric study with an aim to determine the frequency and clinical relevance of ALK alterations detected using targeted next-generation sequencing in patients with advanced ALK-rearranged NSCLC after progression during an ALK TKI treatment. Data on clinical, pathological, and molecular characteristics and patient outcomes were collected., Results: We identified 23 patients with advanced ALK-rearranged NSCLC who, between January 2012 and May 2017, had undergone at least 1 repeat biopsy at progression during an ALK TKI treatment. A resistance mechanism was identified in 9 of the 23 patients (39%). The anomalies involved included 9 ALK mutations in 8 patients and one ALK amplification. The ALK mutation rate was 15% after failure of a first ALK TKI and 33% after failure of 2 ALK TKI treatments. Five of 7 patients who received a different ALK TKI after detection of an ALK mutation achieved an objective response. All of the patients who received a TKI presumed to act on the detected ALK mutant achieved disease control., Conclusion: Targeted next-generation sequencing is suitable for detecting ALK resistance mutations in ALK-rearranged NSCLC patients in routine practice. It might help select the best treatment at the time of disease progression during treatment with an ALK TKI., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objectives The efficacy of osimertinib in pretreated patients with advanced non-small cell lung cancer (NSCLC) harboring EGFR T790 M resistance mutation was demonstrated in clinical trials. However, data on efficacy of osimertinib in real world remain rare. Materials and methods This retrospective multicentric study analyzed T790M-positive advanced NSCLC patients enrolled in French early access program for osimertinib. Patients were pretreated with first- or second-generation EGFR tyrosine-kinase inhibitor and for a majority with chemotherapy. Primary endpoints were progression-free survival (PFS) and overall survival (OS) from osimertinib initiation. Results 205 patients (mean age, 69.5 years; female, 68.8%; adenocarcinoma, 97.5%, never-smokers, 71.5%) were analyzed. Osimertinib was used in second and third line in 18.0% and 82.0% of patients, respectively. Median PFS was 12.4 (95% CI, 10.1-15.1) months. In patients with and without cerebral metastasis, PFS was 9.7 (7.7-13.5) and 15.1 (12.0-17.1) months (p = 0.21), respectively. PFS in second and third line or more was 12.6 (6.7-17.5) and 12.4 (9.7-15.3) months, respectively. Median PFS in patients with EGFR exon 19 deletion and exon 21 mutation was 13.5 (10.1-16.0) and 9.7 (7.4-13.2) months, respectively (p = 0.049). Median OS since osimertinib initiation was 20.5 (16.9-24.3) months: 23.1 (18.6-27.8) and 18.0 (12.2-22.2) months in patients without and with cerebral metastasis (p = 0.11); 17.5 (11.6-27.8) and 21.7 (17.3-24.3) months as second or third line of treatment or more (p = 0.46), respectively. Median OS in patients with EGFR exon 19 deletion and exon 21 mutation was 23.1 (18.6-25.7) and 15.3 (11.6-21.7) months, respectively (p = 0.03). Osimertinib dosage was modified in 8.0% of patients and definitively discontinued for adverse events in 5.9%. Fifty patients benefited from rebiopsy (persistence of T790 M mutation, 44.7%; C797S mutation, 21.1%; cMET amplification, 8.0%). Conclusion In pretreated patients with T790M-mutated advanced NSCLC, the efficacy of osimertinib appears similar in real-world setting to that of clinical trials., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Introduction: The prognostic value of standardized uptake values (SUVs) at initiation of and during chemotherapy remains controversial in lung cancer patients. However, metabolic volume (MV) and total lesion glycolysis (TLG) have shown promise in lung cancer stratification before treatment. Our aim was to define the prognostic value of MV and TLG in a homogenous group of advanced-stage lung cancer patients treated with bevacizumab and paclitaxel., Materials and Methods: Fifty (18)F-fluorodeoxyglucose PET-computed tomography examinations were studied. SUV, MV and TLG were measured for each detectable lesion (classified as primary tumour, node or distant metastasis). MV values were added to compute tumour MV (MVt), nodal MV (MVn), metastatic MV (MVm) and whole-body MV (MVwb). TLGt, TLGn, TLGm and TLGwb were computed using the same method. Maximal SUVt, SUVn, SUVm and SUVwb were measured. Patients were stratified according to each parameter. Overall survival was compared between parameter-stratified groups using the log rank test., Results: At initiation of bevacizumab and paclitaxel therapy (n=12), only TLGwb and TLGn had strong prognostic value with hazard ratios (HRs) of 11.8 and 5.6, respectively (P<0.03). During treatment with bevacizumab and paclitaxel (n=38), SUVwb (HR: 4.9), MVwb (HR: 4.9), TLGwb (HR: 8.9), SUVt (HR: 15.1), MVt (HR: 15.6) and TLGt (HR: 15.6) had significant prognostic value (P<0.05). Metastasis measurements showed no significant prognostic value., Conclusion: MV and TLG are powerful prognostic factors in advanced-stage lung adenocarcinoma being treated with chemotherapy. Focusing on the intrathoracic primary tumour increases the prognostic value of PET in these patients.

Objectives: To determine whether CT can depict early perfusion changes in lung cancer treated by anti-angiogenic drugs, allowing prediction of response., Methods: Patients with non-small cell lung cancer, treated by conventional chemotherapy with (Group 1; n = 17) or without (Group 2; n = 23) anti-vascular endothelial growth factor (anti-VEGF) drug (bevacizumab) underwent CT perfusion before (TIME 0) and after 1 (TIME 1), 3 (TIME 2) and 6 (TIME 3) cycles of chemotherapy. The CT parameters evaluated included: (1) total tumour vascular volume (TVV) and total tumour extravascular flow (TEF); (2) RECIST (Response Evaluation Criteria in Solid Tumours) measurements. Tumour response was also assessed on the basis of the clinicians' overall evaluation., Results: In Group 1, significant reduction in perfusion was identified between baseline and: (1) TIME 1 (TVV, P = 0.0395; TEF, P = 0.015); (2) TIME 2 (TVV, P = 0.0043; TEF, P < 0.0001); (3) TIME 3 (TVV, P = 0.0034; TEF, P = 0.0005) without any significant change in Group 2. In Group 1: (1) the reduction in TVV at TIME 1 was significantly higher in responders versus non-responders at TIME 2 according to RECIST (P = 0.0128) and overall clinicians' evaluation (P = 0.0079); (2) all responders at TIME 2 had a concurrent decrease in TVV and TEF at TIME 1., Conclusion: Perfusion CT demonstrates early changes in lung cancer vascularity under anti-angiogenic chemotherapy that may help predict therapeutic response., Key Points: • Perfusion CT has the potential of providing in vivo information about tumour vasculature. • CT depicts early and specific perfusion changes in NSCLC under anti-angiogenic drugs. • Specific therapeutic effects of anti-angiogenic drugs can be detected before tumour shrinkage. • Early perfusion changes can help predict therapeutic response to anti-angiogenic treatment. • Perfusion CT could be a non-invasive tool to monitor anti-angiogenic treatment.