Chemotherapy In First-line Treatment Research Articles

Higher neutrophil-to-lymphocyte ratio after the first cycle of the first-line chemotherapy is associated with poor cancer specific survival of upper urinary tract carcinoma patients.

BackgroundInflammatory cytokines and immature myeloid derived suppressor cells (MDSCs), which increase during cancer progression, could lead to a neutrophil increase and lymphocyte reduction. Thus, the neutrophil-lymphocyte ratio (NLR) was used to predict survival of patients suffering from urological cancers including upper urinary tract carcinoma. We further determined whether the NLR during the first cycle of first-line chemotherapy could predict cancer specific survival.MethodsWe recruited patients with locally advanced or metastatic upper urinary tract urothelial carcinoma (UTUC) who received chemotherapy between January 2014 and July 2019. We investigated the impact of various clinical variables, including age, sex, performance status, and estimated creatinine clearance (CCr), and NLR before and after the first cycle of the first-line chemotherapy on prognosis.ResultsA total of 41 patients were included in our study. Cancer specific survival of the patients with lower NLR was significantly better than that of the patients with higher NLR measured after the first cycle of the first-line chemotherapy (log-rank test P=0.005, median 29.2 vs. 11.9 months, respectively). Cox proportional regression analysis showed that higher NLR after the first cycle of the first-line chemotherapy was a significant predictor of cancer specific survival.ConclusionsThe NLR after the first cycle of the first-line chemotherapy could be an indication for patients with locally advanced or metastatic UTUC to maintain their first-line chemotherapy treatment.

A multi-centre survey reveals variations in the standard treatments and treatment modifications for head and neck cancer patients during Covid-19 pandemic

BackgroundThe onset of the COVID-19 pandemic necessitated rapid changes to the practice of head and neck oncology in UK. There was a delay between the onset of the pandemic and the release of guidelines from cancer societies and networks, leading to a variable response of individual centres. This survey was conducted to assess the pre-Covid-19 pandemic standard of practice for head and neck oncology patients and the treatment modifications introduced during the first wave of the pandemic in UK. MethodologyThe UK National Cancer Research Institute (NCRI) Head and Neck Clinical Studies Group initiated a multi-centre survey using questionnaire to investigate the effect on feeding tube practice, radiotherapy (RT) fractionation and volumes, use of chemotherapy in the neo-adjuvant, concurrent and palliative setting, the use of immunotherapy in the palliative setting, access to radiology and histopathology services, and availability of surgical procedures. Results30 centres were approached across UK; 23 (76.7%) centres responded and were included in the survey. There were differences in the standard practices in feeding tube policy, RT dose and fractionation as well as concurrent chemotherapy use. 21 (91%) participating centres had at least one treatment modification. 15 (65%) centres initiated a change in radical RT; changing to either a hypofractionation or acceleration schedule. For post-operative RT 10 centres (43.5%) changed to a hypofractionation schedule. 12 (52.2%) centres stopped neo-adjuvant chemotherapy for all patients; 13 (56.5%) centres followed selective omission of chemotherapy in concurrent chemo-radiotherapy patients, 17 (73.9%) centres changed first-line chemotherapy treatment to pembrolizumab (following NHS England’s interim guidance) and 8 (34.8%) centres stopped the treatment early or offered delays for patients that have been already on systemic treatment. The majority of centres did not have significant changes associated with surgery, radiology, histopathology and dental screening. ConclusionThere are variations in the standard of practice and treatment modifications for head and neck cancer patients during Covid-19 pandemic. A timely initiative is required to form a consensus on head and neck cancer management in the UK and other countries.

Crizotinib Versus Conventional Chemotherapy in First-Line Treatment for ALK-Positive Non-Small Cell Lung Cancer: A Systematic Review and Meta-Analysis.

IntroductionLung cancer is the most frequently diagnosed type of cancer and the main cause of death from malignant neoplasms worldwide. One of the most recent discoveries in the context of non-small cell lung cancer (NSCLC) was the mutation of the anaplastic lymphoma kinase receptor (ALK). This genetic alteration is found in approximately 2–5% of NSCLC patients, and crizotinib was the first targeted therapy discovered for its first-line treatment.ObjectiveTo conduct a systematic review and meta-analysis to estimate the magnitude of the overall survival (OS) and progression-free survival (PFS) from using crizotinib as treatment compared to traditional chemotherapy to guide future decision making.MethodsPRISMA and Cochrane recommendations were followed using the findings based on studies published in the main international electronic databases. Selection criteria included the following: randomized clinical trials (RCT) or cohort studies that had assessed the efficacy and effectiveness of crizotinib as monotherapy in patients with NSCLC with ALK fusions.ResultsFrom 2504 publications identified in the literature, only eight publications referring to seven studies met the selection criteria, with high heterogeneity identified between the studies. Overall, there was a significant gain in PFS (HR 0.38; 95% CI 0.30–0.49; p < 0.00001); however, there was no significant gain in OS (HR 0.68; 95% CI 0.43–1.08; p = 0.10).ConclusionThe study highlighted and confirmed that treatment with crizotinib led to clinical improvement in PFS among patients with advanced NSCLC with ALK fusion, as previously reported. However, there was no increase in overall survival in patients with NSCLC with genetic alterations of ALK. This must be considered when reviewing and funding treatments for NSCLC patients with this mutation.

Atezolizumab Monotherapy or Plus Chemotherapy in First-Line Treatment for Advanced Non-Small Cell Lung Cancer Patients: A Meta-Analysis.

BackgroundAtezolizumab plus chemotherapy has been recommended as a first-line treatment option for patients with advanced non-small cell lung carcinoma (NSCLC) irrespective of programmed cell death-ligand 1 (PD-L1) expression. Currently, little is known about the efficacy and treatment-related adverse effects (TRAEs) of subtracting chemotherapy from the combination for patients with high PD-L1 expression. Thus, we performed an indirect comparison between atezolizumab plus chemotherapy and atezolizumab alone.MethodsA total of five eligible randomized controlled trials (RCTs) were identified from PubMed, EMBASE, and Cochrane Central controlled trial registries, using keywords including atezolizumab, PD-1, PD-L1, NSCLC, and RCT. The clinical outcomes of objective response rate (ORR), progression-free survival (PFS), OS, and TRAEs were extracted and evaluated. Using indirect analysis, the efficacy and TRAEs were compared between arm A (atezolizumab plus chemotherapy) and arm C (atezolizumab), linked by arm B (chemotherapy).ResultsDirect comparison revealed that both atezolizumab plus chemotherapy (HR 0.65, P = 0.003) and atezolizumab alone (HR 0.59, P = 0.010) significantly improved OS compared with chemotherapy. More importantly, the indirect comparison showed that atezolizumab plus chemotherapy was not superior to atezolizumab regarding OS (RR 1.10, P =0.695) and ORR (RR 1.11, P = 0.645). However, patients who received atezolizumab combined with chemotherapy experienced more ≥ grade 3 TRAEs (RR 4.23, P<0.001) and TRAEs leading to drug discontinuation (RR 3.60, P<0.001) than those treated with atezolizumab monotherapy.ConclusionsAtezolizumab monotherapy might be a better treatment option for patients with advanced NSCLC and high PD-L1 expression than atezolizumab plus chemotherapy.

PCN183 A Cost-Effectiveness Analysis of Nivolumab plus Ipilimumab plus Two Cycles of Platinum Doublet-Chemotherapy Versus Platinum Doublet Chemotherapy in the First-Line Treatment of Stage IV or Recurrent Non-Small Cell Lung Cancer in Canada

To evaluate the cost-effectiveness of nivolumab plus ipilimumab in combination with two cycles of platinum doublet chemotherapy (NIVO+IPI+PDC) versus four cycles of platinum doublet chemotherapy (PDC) in first-line (1L) treatment for stage IV or recurrent non-small cell lung cancer (NSCLC) from a Canadian healthcare payer perspective.

PD-1/PD-L1 inhibitors plus chemotherapy versus bevacizumab plus chemotherapy as first-line treatment for advanced nonsquamous non-small cell lung cancer: A Bayesian network meta-analysis of randomized controlled trials.

e21152 Background: Chemotherapy in combination with PD-1/PD-L1 inhibitor or bevacizumab have demonstrated superior efficacy to chemotherapy in the first-line treatment for non-squamous non-small-cell lung cancer (NS-NSCLC). However, there has been no randomized study comparing PD-1/PD-L1 inhibitors plus chemotherapy (immune-chemo) with bevacizumab plus chemotherapy (bev-chemo). Thus, we performed this network meta-analysis (NMA) to evaluate the comparative efficacy and safety of immune-chemo and bev-chemo as first-line treatment for NS-NSCLC. Methods: The randomized controlled trials (RCTs) were identified by searching PubMed, Embase, the Cochrane library, and conference abstracts until Oct 2020. Bayesian NMA with fixed effect consistency model was applied to estimate hazard ratio (HR) and Odds ratio (OR) with their 95% confidence intervals (CIs). The outcomes included progression-free survival (PFS), overall survival (OS), overall response rate (ORR), and grade ≥3 treatment-related adverse events (TRAEs). Results: 15 RCTs involving 6541 advanced NS-NSCLC patients were eligible for analysis. For OS, immune-chemo (HR 0.70, 95% CI 0.64-0.79) and bev-chemo (0.87, 0.79-0.95) significantly prolonged survival compared with chemotherapy. For PFS, immune-chemo (0.58, 0.53-0.62) and bev-chemo (0.66, 0.61-0.71) were significantly superior to chemotherapy. For ORR, immune-chemo (2.42, 1.93-3.08) and bev-chemo (2.27, 1.75-2.92) were associated with better benefits than chemotherapy. However, immune-chemo (1.61, 1.08-2.35) and bev-chemo (1.83, 1.08-2.90) increased grade ≥3 TRATEs compared with chemotherapy. The results of Bayesian NMAs shown that immune-chemo (PFS: 0.88[0.80-0.97]; OS: 0.81[0.72-0.92]) was associated with better outcomes than bev-chemo, while there were no significant differences in ORR and the risk of grade ≥3 TRATEs (Table). Conclusions: Immune-chemo and bev-chemo are superior to chemotherapy in first-line treatment of NS-NSCLC. Immune-chemo could significantly improve clinical outcomes compared with bev-chemo without higher severe TRAEs. [Table: see text]

Association of cell-free DNA dominant clone allele frequency with poor outcomes in advanced biliary cancers treated with platinum-based chemotherapy.

4079 Background: Cell-free circulating tumor DNA (ctDNA) holds significant promise and is being used for clinical decision making in multiple tumors. This study aimed to evaluate the prognostic value of pre-treatment ctDNA in metastatic biliary tract cancers (BTC) treated with platinum based first-line chemotherapy treatment. Methods: We performed a retrospective analysis of 67 patients who underwent ctDNA testing before platinum-based chemotherapy for first-line treatment for metastatic BTC. For analysis we considered the detected gene with highest variant allele frequency (VAF). Results of ctDNA analysis were correlated with patients’ demographics, progression-free survival (PFS) and overall survival (OS). Results: The median age of patients was 67 y/o (27-90). 54 (80.6%) of 67 patients evaluated had intrahepatic cholangiocarcinoma; seven had extrahepatic cholangiocarcinoma and six gallbladder cancer. 46 (68.6%) of the patients were treated with cisplatin plus gemcitabine, 14 (21%) patients received gemcitabine and other platinum (carboplatin or oxaliplatin) combinations while 7 (10.4%) patients were treated on a clinical trial with gemcitabine and cisplatin plus additional targeted agents (CX4945 or PEGPH20). TP53, KRAS, APC, FGFR2 and IDH1 were the genes with highest frequency as dominant clone. The median dominant clone allele frequency (DCAF) was 3% (0-97%). DCAF &gt;3% was associated with statistically significant worse PFS (median PFS: 4.05 vs. 7.70 months, p=0.046) and OS (median OS: 10.8 vs. 18.8 months, p=0.056). Each 1% increase in DCAF is associated with a hazard ratio of 26.21 in OS when adjusting for subtypes, age, treatment type, and CA19-9 [Table]. Conclusions: Patients with metastatic BTC with DCAF &gt; 3% at diagnosis have worse PFS and OS compared to patients with low ctDNA when treated with upfront platinum-based chemotherapy.[Table: see text]

Analysis of the relationship between different prognosis factors in patients with advanced colon cancer and progression-free survival.

e15518 Background: Colon tumors are a heterogeneous group of disease. As a result of the accumulation of different genetic and epigenetic alterations, the mutation of the RAS, BRAF oncogene and microsatellite instability stands out. A new line of research are immunological and inflammatory factors, the infiltrating lymphocytes of the tumor stroma (TILs) and the neutrophil to lymphocyte radio (NLR) have been studied by our work team. We understood could that these factors were associated with the survival rate in our patients. The main objective of this reseach is to determine the relationship between NLR and progression-free survival (PFS) in patients with advanced colon cancer. Secondary objective is to determine the relationship between the location of the primary tumor, RAS status, TILs, and PFS. in the same group of patients. Methods: A total of 93 medical records of patients with advanced colon cancer was analyzed. Those pts who had recieved first-line chemotherapy treatment with a FOLFOX scheme plus a monoclonal antibody were included. All patients had to have a minimum follow-up of 12 months. Regarding NLR, the patients were classified into two groups: high ( = &gt; 4) and low ( &lt; 4). Four TILs cut-off points were determined: &gt; 40% intense; between 11-40% moderate, 1-10% mild, and 0% absent, which were group into two categories: intense and moderate; slight and absent. Localization was divided into left and right, and KRAS status was divided into mutated and wild-type (WT). PFS was calculated using the Kaplan-Meier test. Results: The median PFS of the general population was 8.74 (7.39-11.07) months. The median PFS was 9.86 (7.82-13.41) vs 5.09 (4.43-10.84) months for low and high NLR respectively, with statistical significance (p: 0.01). When the percentage of patients without progression after one year of treatment was analyzed, the difference was 45% vs 14% in favor of NLR &lt; 4 on ≥4, this difference was also statistically significant (p: 0.02). PFS in relation to TILs after one year of follow up was 33% (8.61 months) for moderate-intense infiltrate vs 30% of mild-absent (7.10 months). PFS was 9.79 months for KRAS WT pts vs 7.82 months for mutated KRAS. In terms of location, PFS was 9.79 months for the left colon vs 8.28 months for the right colon. These factors did not have a statistically significant difference. Conclusions: The results of the study show how NLR &lt; 4 is a prognostic factor with a positive impact on PFS. It should be noted that the median survival rates were numerically higher in moderate-intense vs mild-absent TILs, also in KRAS WT vs mutated and in left vs right location. It should also be noted that the possibly there was not a statistically significant difference between them due to the limited number of patients per what we will continue working on in the recruitment and analysis of these patients.

520P Anti-angiogenic agents in combination with chemotherapy in first-line treatment of small cell lung cancer: A systematic review and meta-analysis

520P Anti-angiogenic agents in combination with chemotherapy in first-line treatment of small cell lung cancer: A systematic review and meta-analysis

P03.03 MERMAID-1: A Phase III Study of Adjuvant Durvalumab plus Chemotherapy in Resected NSCLC Patients with MRD+ Post-Surgery

30% of non-small-cell lung cancer (NSCLC) patients present with surgically resectable disease at diagnosis. To reduce disease recurrence, adjuvant chemotherapy is standard of care (SoC) for patients with completely (R0) resected stage II/III NSCLC. However, 5-year disease-free survival (DFS) rates remain low (∼40%), with a 5-year absolute benefit of only 5.4% derived from chemotherapy (Pignon et al. JCO 2008;26:3552-9). Determining who will benefit from adjuvant chemotherapy remains challenging. Identifying minimal residual disease (MRD) through detection of circulating tumour (ct) DNA post-surgery could predict early disease recurrence. Durvalumab is a selective, high-affinity, human IgG1 monoclonal antibody that blocks PD-L1 binding to PD-1 and CD80. In the phase III PACIFIC trial of patients with unresectable, stage III NSCLC without disease progression following radical platinum-based concurrent chemoradiotherapy, durvalumab improved progression-free survival (PFS) and overall survival (OS), demonstrating its efficacy in situations of residual disease. Further, initial data from POSEIDON showed durvalumab plus chemotherapy prolongs PFS versus chemotherapy in first line treatment of metastatic NSCLC. In the adjuvant setting (i.e. following complete tumour resection), this regimen could provide additional DFS benefit versus chemotherapy alone. MRD assessment could facilitate earlier, more selective adjuvant therapy for MRD+ patients, allowing for treatment intensification for this potentially biologically distinct disease, while minimising overtreatment of MRD– patients. MERMAID-1 will investigate the efficacy and safety of adjuvant durvalumab + SoC chemotherapy versus placebo + SoC chemotherapy in patients with completely resected stage II/III NSCLC, to assess the benefits of adjuvant therapy in patients with MRD+ status. MERMAID-1 (NCT04385368) is a phase III, parallel-arm, placebo-controlled, double-blind, multicentre study, conducted across 16 countries. Patients aged ≥18 years with histologically confirmed EGFR-/ALK- Wild-type, stage II/III NSCLC will enter the first screening period; a personalised MRD panel will be created. Before randomisation, and following assessment of MRD status post-surgery, patients will be further screened for full eligibility (no evidence of disease recurrence, WHO/ECOG performance status 0/1). Patients who have received prior adjuvant therapy or durvalumab, and those with mixed small cell and NSCLC histology or evidence of post-operative disease recurrence are ineligible. MRD status will be determined via ctDNA analysis of plasma samples, collected 3–4 weeks post-surgery, and based on personalised panels (comprised of ≤50 tumour-specific DNA variants) created by whole exome sequencing analysis of the patient’s resected tumour tissue. Approximately 332 patients will be randomised 1:1 (stratified by disease stage, MRD status, and PD-L1 expression) to durvalumab (1500 mg, intravenously) or placebo, plus concurrent SoC chemotherapy, once every three weeks (Q3W) for 12 weeks. Patients will continue with durvalumab monotherapy/placebo Q4W thereafter, until Week 48 or disease recurrence, whichever occurs first. Following a baseline radiological scan prior to randomisation, patients will be assessed Q12W until disease recurrence (per RECIST v1.1). The primary endpoint is DFS in the MRD+ analysis set (investigator-assessed). Secondary endpoints include DFS in the full analysis set (FAS; investigator-assessed); DFS in the MRD+ analysis set and FAS (blinded independent central review); OS in the MRD+ analysis set and FAS; and safety and tolerability, and patient-reported outcomes. adjuvant therapy, minimal residual disease, PD-L1

P86.02 Pyrotinib Combined with Apatinib for HER2-Mutant Non-Small Cell Lung Cancer: Interim Analysis from a Phase II Clinical Study

Currently, there has been no approved tyrosine kinase inhibitors (TKIs) for non-small cell lung cancer (NSCLC) harboring HER2 mutations, resulting in an unmet need of this molecular entity. We performed this phase II study to assess the efficacy and safety of pyrotinib combined with apatinib in HER2-mutant advanced NSCLC patients who had failed to prior treatment. Patients with metastatic HER2-mutant lung adenocarcinomas who had been pretreated with chemotherapy or other TKIs were enrolled to administer pyrotinib (dose of 400mg once daily) in combination with apatinib (dose of 250mg once daily) for 28-day cycles. The primary endpoint was objective response rate (ORR), and the second endpoint included progression-free survival (PFS), duration of response (DoR), disease control rate (DCR), overall survival (OS) and safety. The trial was approved by ethics committee and registered to Chinese Clinical Trial Registry (ChiCTR1900021684). All participants of this study provided written informed consent. Between March 5, 2019, and January 20, 2020, 14 patients were enrolled and received pyrotinib with apatinib combination therapy, and all of them were stage IV at baseline. Seven (50.0%) patients had received first-line platinum-based chemotherapy or afatinib treatment, and the others had received at least 2 lines of prior therapy (range, 2-6). At the last follow-up time July 14, 2020, among these 14 evaluable patients, the ORR was 35.7% (5/14), and it showed no difference between patients with or without brain metastases (ORR, 40.0% vs 33.3%; median PFS, 6.6 vs. 8.0 months, P = 0.623). All subgroups of patients (10 with exon 20 insertions, 2 with missense mutations and 2 with amplifications) showed disease control with a DCR of 100%. The median PFS, DoR and OS were 8.0 (95%CI: 5.8-10.2), 5.3 (95%CI: 3.6-7.0) and 12.9 (95%CI: 3.8-22.0) months, respectively. The ORR in patients who administered pyrotinib with apatinib as second-line and third- or above-line treatment was 28.6% (2/7) and 42.9% (3/7), respectively; and median PFS did not differ in these two subgroups [8.8 (95%CI: 6.6-11.0) vs. 6.1 (95%CI: 4.0-8.2) months; HR=0.362; P = 0.144]. Common treatment-related adverse events included diarrhea (7.1%, grade 3; 64.3%, grade 2), hypertension (21.4%, grade 2; 50.0%, grade 1) and anorexia (57.1%, grade 1). No treatment-related deaths were reported. Patient characteristics at baseline and response for pyrotinib with apatinibTabled 1ParametersGroupsN (%)Age>602 (14.3)≤6012 (85.7)GenderMale7 (50.0)Female7 (50.0)Molecular variantA775_G776insYVMA9 (64.3)P780_Y781insGSP1 (7.1)G776V1 (7.1)R811L with Q820K1 (7.1)HER2 amplification2 (14.4)Prior lines of treatment17 (50.0)23 (21.4)≥34 (28.6)Brain metastasesPresence5 (35.7)Absence9 (64.3)Partial responseG766V HER2 amplification A775_G776insYVMA1 (7.1) 1 (7.1) 3 (21.4) Open table in a new tab Pyrotinib in combination with apatinib showed favorable antitumor activity and acceptable safety in heavily pretreated NSCLC patients with diverse HER2 mutations.

A Scoring System Based on Nutritional and Inflammatory Parameters to Predict the Efficacy of First-Line Chemotherapy and Survival Outcomes for De Novo Metastatic Nasopharyngeal Carcinoma.

PurposeWe aimed to develop a simple scoring system based on baseline inflammatory and nutritional parameters to predict the efficacy of first-line chemotherapy and survival outcomes for de novo metastatic nasopharyngeal carcinoma (mNPC).Patients and MethodsWe retrospectively collected ten candidate inflammatory and nutritional parameters from de novo mNPC patients who received platinum-based first-line chemotherapy treatment. We examined the effects of these ten candidate variables on progression-free survival (PFS) using the Cox regression model. We built a risk-scoring system based on the regression coefficients associated with the identified independent prognostic factors. The predictive accuracy of the scoring system was evaluated and independently validated.ResultsA total of 460 patients were analyzed. Four independent prognostic factors were identified in a training cohort and were used to construct the scoring system, including nutritional risk index, C-reactive protein level, alkaline phosphatase level, and lactate dehydrogenase level. Based on the score obtained from the scoring system, we stratified patients into three prognostic subgroups (low: 0–1 point, intermediate: 2–3 points, and high: 4 points) associated with significantly different disease control rates (94.7% vs. 92.5% vs. 66.0%, respectively) and survival outcomes (3-year PFS: 55.8% vs. 29.1% vs. 11.9%, respectively). The scoring system had a good performance for the prediction of short-term disease control (area under the receiver operating characteristic curve [AUC]: 0.701) and long-term survival outcomes (time-dependent AUC for 5-year PFS: 0.713). The results were internally validated using an independent cohort (AUC for predicting disease control: 0.697; time-dependent AUC for 5-year PFS: 0.713).ConclusionWe developed and validated a clinically useful risk-scoring system that could predict the efficacy of first-line chemotherapy and survival outcomes in de novo mNPC patients. This system may help clinicians to design personalized treatment strategies.

Immune Checkpoint Inhibition in Oesophago-Gastric Carcinoma.

Immune checkpoint inhibitors enrich the therapeutic landscape in oesophago-gastric carcinoma. With regard to oesophageal squamous cell carcinoma (ESCC), the selective PD-1 (programmed cell death receptor 1)-inhibitor nivolumab improves disease-free survival in the adjuvant therapy setting (CHECKMATE-577). In first-line treatment, ESCC patients (pts) benefit in overall survival (OS) from the PD-1-inhibitor pembrolizumab in combination with chemotherapy (KEYNOTE-590). In the second-line setting, nivolumab (ATTRACTION-03) and pembrolizumab (KEYNOTE-181) demonstrate a benefit in OS compared with chemotherapy. These data resulted in the approval of nivolumab for the second-line treatment of advanced ESCC pts regardless of PD-L1 (programmed cell death ligand 1) status in Europe, Asia, and the USA, and pembrolizumab for pts with PD-L1 CPS (combined positivity score) ≥ 10 in Asia and the USA. Further approvals can be expected. In gastro-oesophageal junction and gastric cancer, the addition of nivolumab to chemotherapy in first-line treatment improves OS in pts with advanced disease with PD-L1 CPS ≥ 5 (CHECKMATE-649). Additionally, pembrolizumab was non-inferior to chemotherapy for OS in PD-L1 CPS ≥ 1 pts (KEYNOTE-062). In third-line treatment, nivolumab shows benefits in OS regardless of PD-L1 expression (ATTRACTION-02) with approval in Asia, and pembrolizumab prolonged the duration of response in PD-L1 positive pts (KEYNOTE-059) with approval in the USA. We discuss the recent results of the completed phase II and III clinical trials.

Cemiplimab monotherapy in advanced non-squamous and squamous non-small cell lung cancer

Anti-programmed death 1 (PD-1) and programmed death ligand 1 (PD-L1) monoclonal antibodies are commonly used for advanced non-squamous and squamous non-small cell lung cancer, preferably in patients with high PD-L1 expression (tumour proportion score [TPS] ≥50%) and no targetable driver mutations in epidermal growth factor receptor (EGFR), MET exon 14 skipping alterations, or gene fusions in ALK, ROS1, RET, and TRK.1 In the phase 3 KEYNOTE-024 study, pembrolizumab significantly improved progression-free survival and overall survival compared with platinum-based chemotherapy in first-line treatment of advanced non-small cell lung cancer patients with a TPS score of 50% or greater.

Meta-analysis of the Efficacy and Tolerability of Immune Checkpoint Inhibitors Combined With Chemotherapy in First-line Treatment of Small Cell Lung Cancer

PurposeThe present study was conducted to evaluate the efficacy and tolerability of using an immune checkpoint inhibitor (ICI; programmed cell death protein 1/ligand 1 [PD-1/PD-L1] inhibitor or cytotoxic T-lymphocyte antigen [CTLA]-4 inhibitor) combined with chemotherapy in the first-line treatment of small cell lung cancer. MethodsPotential articles and studies were identified using Web of Science, Cochrane Library, and ClinicalTrials.gov. The end points included overall survival, progression-free survival, objective response rate, and adverse events. Significant heterogeneity was represented by a P value (Ph) of <0.05 or an I2 value of ≥50%, and the random-effects model was applied for pooled analysis. Otherwise, the fixed-effects model was used. Subgroup analysis was performed based on the type of ICI. Potential publication bias was evaluated via funnel plot and the Egger test. FindingsFive eligible articles were included. Both overall survival (hazard ratio [HR] = 0.83; 95% CI, 0.75–0.91; P < 0.001) and progression-free survival (HR = 0.80; 95% CI, 0.73–0.86; P < 0.001) were significantly prolonged by joint ICI + chemotherapy treatment. Additionally, the rates of tolerable grade ≥3 adverse events were similar between the ICI combination regimens and conventional chemotherapy (relative risk = 1.05; 95% CI, 0.98–1.12; P = 0.17). Subanalysis demonstrated that patient survival and objective response rate were more efficiently improved with a combination of anti–PD-1/PD-L1, but not anti–CTLA-4, + chemotherapy. ImplicationsBased on data from the available literature, clinical efficacy (as measured by patient survival and objective response rate) was improved with a combination of anti–PD-1/PD-L1 + chemotherapy as first-line treatment compared with chemotherapy alone in patients with small cell lung cancer.

Central Nervous System Lymphomas.

Primary central nervous system (CNS) lymphoma is a rare, aggressive extranodal non-Hodgkin lymphoma confined to the brain, eyes, CSF, or spinal cord without systemic, non-CNS involvement. This article reviews the clinical presentation, imaging characteristics, diagnostic workup, novel pathophysiologic insights, and treatment of immunocompetent patients with primary CNS lymphoma. The prognosis of primary CNS lymphoma has significantly improved over the past few decades because of the introduction of and widespread use of high-dose methotrexate, which is now the backbone of all first-line combination chemotherapy treatments. Despite this progress, durable remission is still observed in only approximately 50% of patients. Novel insights into the pathophysiology of primary CNS lymphoma have identified the B-cell receptor pathway as well as the suppressed tumor immune microenvironment and immune evasion as key mechanisms in the pathogenesis of primary CNS lymphoma. Novel, small molecules and agents targeting these aberrant pathways have been introduced into clinical trials of recurrent/refractory primary CNS lymphomas. Agents such as the Bruton tyrosine kinase (BTK) inhibitor ibrutinib or immunomodulatory drugs such as lenalidomide and pomalidomide have shown promising response rates in the relapsed setting. Diagnosis of primary CNS lymphoma requires a high level of suspicion because clinical signs and deficits can vary and depend on the involved CNS compartments. Rapid initiation of therapy is essential for recovery and prognosis. The optimal treatment regimen has not been defined, but methotrexate-based chemotherapy regimens are considered the standard treatment approach for induction treatment. Novel, targeted agents have recently been introduced into the therapeutic arsenal.

Combination of trastuzumab and taxane-containing intensified chemotherapy in first-line treatment of HER2-positive advanced gastric cancer.

Taxane-containing combinations are recommended for the first-line therapy of advanced gastric cancer. It is not known which chemotherapy regimen is the best with trastuzumab for HER2-positive patients. The aim of this study was to compare taxane-containing intensified chemotherapy versus standard chemotherapy in combination with trastuzumab in the first-line treatment of HER2-positive advanced gastric adenocarcinoma. This study is a retrospective multicenter study of the Turkish Oncology Group. A total of 130 HER2-positive patients with inoperable locally advanced, recurrent, or metastatic gastric adenocarcinoma being given chemotherapy plus trastuzumab as the first-line treatment were included from 16 different oncology centers. Trastuzumab combination with intensified chemotherapy including taxane or standard chemotherapy was compared in terms of progression-free survival (PFS), overall survival (OS), and toxicity. There were 108 patients in the standard and 22 patients in the intensified chemotherapy group. PFS of the standard and intensified group were 5.6 months (95% confidence interval [CI] 4.8-6.4) and 5.3 months (95% CI 2.6-8), respectively (p = 0.70). OS of the standard and intensified group were 11.1 months (95% CI 8.3-13.9) and 15.2 months (95% CI 12.7-17.7), respectively (p = 0.03). Repeated analysis excluding patients given any previous therapy revealed similar results. The intensified group had more fever and febrile neutropenia. Trastuzumab combination with intensified chemotherapy provides better OS in first-line treatment of HER2-positive advanced gastric cancer. Further large-scale studies should be performed in HER2-positive patients.

Correlation Between Baseline Serum Tumor Markers and Clinical Characteristic Factors in Patients with Advanced Pancreatic Cancer.

PurposeIn pancreatic cancer (PC), CA 19–9, CEA and CA 125 are the most widely used tumor markers. The aim of this study was to explore the prognostic significance of baseline levels of serum CA 19–9, CEA, and CA 125, and to evaluate the clinical significance of these markers in PC patients.Patients and MethodsA total of 278 patients with advanced PC that had received first-line chemotherapy treatments were examined. Correlation analysis between the tumor markers and clinical characteristics was performed using a Pearson’s Chi-squared test or Fisher’s exact test. A Pearson’s correlation test was utilized to investigate the relationship between tumor markers and peripheral blood parameters. Univariate analysis was estimated using a Kaplan–Meier analysis and compared using a Log rank test. Multivariate analysis was performed using a Cox proportional hazards regression model.ResultsBoth individually and collectively, the baseline CA 19–9, CEA and CA 125 levels were positively associated with the primary tumor site (p < 0.01), liver metastasis (p < 0.05), and number of organ metastases (p < 0.05). Furthermore, CA 19–9, CEA and CA 125 were correlated to baseline WBC (p < 0.001) and LDH (p < 0.01) levels. Additionally, CA 19–9 was correlated with years of smoking (p = 0.024); diabetes and years of diabetes (p = 0.012); baseline glycemic levels (p = 0.004); and neutrophil counts (p < 0.001). Moreover, CA 125 levels were associated with the baseline neutrophil counts (p < 0.001) and peritoneal metastasis (p = 0.008). When examining neutrophil, LDH, CA 19–9 and CA 125 levels were found to be associated with overall survival (OS) and shown to be independent prognostic factors.ConclusionCA 19–9, CEA and CA 125 are correlated with multiple clinical factors. Baseline neutrophil, LDH, CA 19–9 and CA 125 levels are associated with OS and may potentially serve as prognostic factors.

Les patients ALK et ROS1 : quelle séquence ?: ALK and ROS1 patients: What sequence?

AbstractCrizotinib is a tyrosine kinase inhibitor of ALK (iALK) more effective and better tolerated that chemotherapy in first-line treatment of advanced non-small cell lung cancer with ALK fusion (ALK+ NSCLC). Crizotinib resistance will eventually occur in all patients. This is about on target resistance mutations in one third of the cases, bypass pathway emergence in one third and central nervous system progression in one third. Next generation iALK (ceritinib, alectinib, brigatinib, lorlatinib, ensartinib) are effective at time of crizotinib failure. The “classic” iALK sequencing with crizotinib followed by next generation iALK is associated with survival from diagnosis of metastatic disease exceeding 4 years. The second-generation iALK alectinib and brigatinib demonstrated their superiority compared to crizotinib in terms of progression-free survival, tolerability and cerebral disease control. This result paves the way for a new standard of care with alectinib/brigatinib front-line followed by lorlatinib. Crizotinib is the standard of care in ROS1+ NSCLC. Treatment at time of crizotinib failure is not well settled.© 2020 SPLF. Published by Elsevier Masson SAS. All rights reserved.

LBA57 MHC-II antigen presentation pathway as a predictive biomarker for sintilimab plus chemotherapy in first-line treatment of locally advanced or metastatic non-squamous non-small cell lung cancer (nsq-NSCLC)

LBA57 MHC-II antigen presentation pathway as a predictive biomarker for sintilimab plus chemotherapy in first-line treatment of locally advanced or metastatic non-squamous non-small cell lung cancer (nsq-NSCLC)