Pharmaceutical, Eli Lilly, Taiho Pharmaceutical, AstraZeneca, Boehringer-Ingelheim, MSD, Novartis; Personal fees: Daiichi Sankyo Healthcare, Merck Serono; Grants: Astellas, outside the submitted work. T. Tokito: Honoraria: AstraZeneca, MSD, Ono, Chugai. T. Takahashi: Grants, personal fees: Ono Pharmaceutical Co., Ltd., MSD K.K., AstraZeneca KK, Chugai Pharmaceutical Co., Ltd., Eli Lilly Japan K.K.; Grants: Pfizer Japan Inc.; Personal fees: Boehringer Ingelheim Japan, Inc, Roche Diagnostics K.K. K. Kasahara: Grants, honoraria: Boehringer Ingelheim; Honoraria: Pfizer, Chugai Pharmaceutical, Eli Lilly, Taiho Pharmaceuticals, AstraZeneca, MSD. Y. Hattori: Research funding: MSD, Ono; Honoraria: AstraZeneca, Boehringer Ingelheim, Chugai, Eli Lilly, MSD, Novartis, Ono, Taiho. E. Ichihara: Research grants: Eli Lilly, MSD. N. Adachi, T. Sawada, T. Shimamoto, K. Noguchi: Employee: MSD K.K., Tokyo, Japan. M.C. Pietanza: Employee: Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA. T. Kurata: Research grants: AstraZeneca, MSD; Honoraria: AstraZeneca, MSD, Ono, Bristol-Myers Squibb, Chugai, Eli Lilly.
152P Correlation among different KRAS alterations, genetic co-mutations and PD-L1 expression in patients treated with immunotherapy in metastatic NSCLC L. Gianoncelli1 , G. Spitaleri1 , A. Passaro1 , C. Fumagalli2 , P. Trillo Aliaga1 , E. Del Signore1 , V. Stati1 , E. Ferraro1 , E. Guerini-Rocco2 , C.M. Catania1 , M. Barberis2 , F. de Marinis1 1
Division of Thoracic Oncology, European Institute of Oncology, Milan, Italy,2 Division of Pathology & Laboratory Medicine, European Institute of Oncology, Milan, Italy Background: No molecularly driven strategy against KRAS demonstrated convincing activity in clinical trials. The introduction of immune checkpoints inhibitors (IO) rep-resents a paradigm shift in treatment of NSCLC without gene target. Considering the association with smoke, the high mutational burden, the high PDL1 expression and the abundance of T-cell infiltrating lymphocyte, KRAS mutant tumors have been consid-ered an attractive target for IO.
Methods: Patients (pts) with stage IV NSCLC harboring KRAS mutation treated with IO in our Institution between 2016 and 2018 were retrospectively identified by elec-tronic medical record review. All pts provided written informed consent for the collec-tion of clinical, demographic and molecular data.
Results: A total number of 328 consecutive pts with KRAS mutant NSCLC were identi-fied, of them 32 received IO. All eligible pts had PDL1 testing and in 21 cases (65.6%) NGS was available. Median age was 63 (range 44-78). Male/female were 17/15. Most pts had an adequate ECOG PS (0/1 18.7%/65.6% respectively). 29 pts (90.6%) were smok-ers. According to the setting, 10 pts were treated in 1st-line, 9 in 2nd-line and 13 in fur-ther lines. Between the 9 subtypes of KRAS mutation identified in our cohort, G12C was the commonest (14, 43.8%). 15 pts (46.9%) had PDL150%, 10 (31.2%) had PD-L1 between 1-49%, and 7 (21.9%) were negative. 8 pts (25%) had co-occurring gene mutations. With a median follow-up of 5.1 mos (0.4-28.6), the mPFS and mOS for ITT population were 4.47 (95% CI 2.5-6.4) and 7.73 (95% CI 6-14.5) mos.
Conclusions: Our preliminary results, contrary to findings in other oncogene driven NSCLC, showed that the presence of KRAS mutations seems to be irrelevant for the selection of patients for IO. Furthermore, neither the association of co-mutation (found in the 25% of cases) nor the type of KRAS variant or the treatment setting (1st vs further lines) seems to have an impact on the effectiveness of IO in KRAS NSCLC pts. Data about clinical efficacy according to PD-L1 expression will be presented at the meeting.
Legal entity responsible for the study: The authors. Funding: Has not received any funding.
Disclosure: All authors have declared no conflicts of interest.
153P Chemotherapy with immune-checkpoint inhibitors in first-line treatment metastatic NSCLC patients: Systematic review and literature-based meta-analysis A. Addeo1 , G.L. Banna2 , G. Metro3 , M. Di Maio4 1
Hoˆpitaux Universitaires de Gene`ve - HUG, Geneva, Switzerland,2
Oncology, Cannizzaro Hospital, Catania, Italy,3
Medical Oncology, Azienda Ospedaliera di Perugia S. Maria della Misericordia, Perugia, Italy,4
Oncology, Azienda Ospedaliera Mauriziano Umberto I, Turin, Italy
Background: Checkpoint inhibitors plus platinum-based chemotherapy have shown superiority compared to chemotherapy alone as first-line therapy in advanced non– small cell lung carcinoma (NSCLC), but little is known about the real benefit within the different PDL1 expression subgroups. Our aim was to estimate the relative benefit in term of Overall Survival (OS) and Progression-free Survival (PFS) of checkpoint inhib-itors plus chemotherapy versus chemotherapy alone, overall and in subgroups defined by PDL1 expression.
Methods: This meta-analysis searched PubMed and checked references of articles to iden-tify trials that combined checkpoint with chemotherapy versus chemotherapy in the first-line setting. For each trial included in this study, the trial name, year of publication or con-ference presentation, patients’ clinic-pathological characteristics, type of chemotherapy, type of checkpoint inhibitor and PDL1 expression were extracted. Data collection took place from October 1th to October 24th, 2018. A random-effects model was applied.
Results: Eight trials with advanced NSCLC were included in this meta-analysis. Checkpoint inhibitors plus chemotherapy were associated with prolonged OS, com-pared with chemotherapy in the ITT population (HR, 0.61; 95% CI, 0.61-0.66; P<.000001). OS was prolonged in the PDL1 0% group (HR, 0.78; 95% CI, 0.67-0.90; P<.0007) and in the PDL1 high (HR, 0.61; 95% CI, 0.48-0.78; P<.00001) but not in the PDL1 low (HR, 0.77; 95% CI, 0.55-0.107; P < 0.12). Chemotherapy plus pembrolizu-mab showed OS benefit (HR, 0.56; 95% CI, 0.40-0.78; P<.00007)in low PD-L1 low, unlike atezolizumab backbone trials (HR, 0.92; 95% CI, 0.62-1.37; P < 0.69). Checkpoint inhibitors plus chemotherapy were associated with prolonged PFS in the ITT (HR, 0.61; 95% CI, 0.56-0.66; P < 0.00001) across PDL1 subgroups.
Conclusions: Checkpoint inhibitors plus chemotherapy compared to chemotherapy, are associated with prolonged OS and PFS in first-line therapy in NSCLC. In low PDL1 subgroup the benefit was statistically significant only in the pembrolizumab backbone trials. The findings of this meta-analysis could assist in the design and interpretation of future trials and in economic analyses.
Legal entity responsible for the study: The authors. Funding: Has not received any funding.
Disclosure: A. Addeo: Consulting role: MSD, Roche, Pfizer, Astrazeneca, BMS, Boehringer Ingelheim; Research grant: Boehringer Ingelheim; Travel grant: Roche, MSD. M. Di Maio: Honoraria for lectures in meeting, participation in Advisory boards: Astellas, Janssen. All other authors have declared no conflicts of interest.
154P Renal toxicity from platinum/pemetrexed and pembrolizumab in the era of combination therapy
D. Dumoulin1 , S. Visser2
, R. Cornelissen3 , J.G. Aerts1 1
Pulmonology, Erasmus MC Cancer Institute, Rotterdam, Netherlands,2 Internal Medicine, Amphia Ziekenhuis-location Molengracht, Breda, Netherlands,3
Erasmus University Medical Center, Rotterdam, Netherlands
Background:Recently, the phase 3 keynote-189 trial showed that in previously untreated patients with advanced non-squamous NSCLC without targetable mutations, the progression-free and overall survival were significantly longer with addition of pembroli-zumab to chemotherapy than with chemotherapy alone. Both chemotherapy and pem-brolizumab can give renal toxicity, which can be a major challenge in the clinical setting. Methods:In a prospective multicenter observational real-life cohort study [Visser Eur Respir J 2018], we evaluated the incidence of acute/chronic kidney disease (AKD/ CKD), its related treatment discontinuation frequency and associated clinical variables with AKD in patients with stage IIIB/IV NSCLC treated with platinum/pemetrexed. In addition, the Keynote 189 toxicity data was used for the combination treatment. We thereafter reviewed literature to generate an algorithm for diagnosis and treatment in increased creatinine levels.
Results:149 patients received pemetrexed platinum, of whom 44 patients (30%) continued maintenance. During induction therapy 48 patients (50%) treated with cisplatinum/peme-trexed developed AKD and 15 patients (29%) treated with carboplatin/pemecisplatinum/peme-trexed. During maintenance 13 patients (30%) developed AKD, leading to CKD and treatment discontinu-ation in eight patients (62%). In the Keynote 189 trial combining pembrolizumab with che-motherapy, nephritis has been reported in 1,7% of patients in any grade (1,5% grade 3-4). However, when looking at an increased blood creatinine in the group that was treated with carboplatin, a total of 12,2% of patients showed any increase (0,7% grade 3-4). Conclusions:Increased blood creatinine levels from pemetrexed and pembrolizumab is a common entity, probably more common in a real-life setting. This elevation is clini-cally challenging in a population that receives three agents that can cause a creatinine increase. Currently, there are no markers to distinguish between renal failure due to chemotherapy of immunotherapy. We will present an algorithm based on current knowledge for clinicians as guidance for renal dysfunction in patients treated with che-motherapy and pd-(l)1 checkpoint inhibitors.
Legal entity responsible for the study:The authors. Funding:Has not received any funding.
Disclosure:D. Dumoulin: Speakers fee: BMS, Roche, Pfizer, Novartis. R. Cornelissen: Consultancy: Roche, Boehringer Ingelheim, BMS, MSD; Speakers fee: Roche, Pfizer, Boehringer Ingelheim, Novartis, BMS. J.G. Aerts: Advisory boards: BMS, Boehringer Ingelheim, MSD, AstraZeneca, Eli Lilly, Takeda, Amphera; Stock owner: Amphera B.V. All other authors have declared no conflicts of interest.
155P Association of immune-related adverse events (irAEs) and immunotherapy (IT) benefit in advanced non-small cell lung cancer (NSCLC)
C. Saavedra Serrano, A. Barquın Garcıa, E. Corral de la Fuente, J.J. Serrano Domingo, V. Albarran Artahona, R. Martin Huertas, A. Gomez Rueda, M.E. Olmedo Garcıa Medical Oncology, Hospital Universitario Ramon y Cajal, Madrid, Spain
Background: IT has improved outcomes in advanced NSCLC. However, this therapy can yield significant toxicity secondary to immune activation. Several retrospective studies have reported a direct relationship between IT efficacy and the development of irAEs, in Response Rate (RR) and survival.
