Serum CYFRA 21-1 as a biomarker of pemetrexed plus cisplatin treatment in nonsquamous non-small cell lung cancer.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e18014-e18014
Author(s):  
Toshio Sakatani ◽  
Fumiyoshi Ohyanagi ◽  
Azusa Tanimoto ◽  
Yuko Kawano ◽  
Ryota Saito ◽  
...  

e18014 Background: Pemetrexed (P) is a key drug in the treatment of advanced non-squamous (N-Sq) non-small cell lung cancer (NSCLC). Although differential efficacies of P between squamous (Sq) and N-sq subtypes have been reported, it is difficult to get a clear histological diagnosis from a small biopsy sample. Therefore, a more objective, yet simple, biomarker for histology-based treatment is needed. Previously, we reported that serum Cytokeratin fragment 21-1 (CYFRA) was related to the outcome of P monotherapy. In this study, we examined whether serum CYFRA could predict the efficacy of the cisplatin-pemetrexed (CP) combination regimen as well as it did for P monotherapy. Methods: Pre-treatment serum concentrations of CYFRA, carcinoembryonic antigen (CEA), squamous cell carcinoma (SCC) antigen, and sialyl Lewis X-I antigen (SLX) were measured in 50 N-sq NSCLC patients who were enrolled in a phase II study of C (75 mg/m2 and 500 mg/m2) against N-Sq NSCLC. Eligibility criteria consisted of histologically or cytologically confirmed recurrent or metastatic N-Sq NSCLC previously untreated with chemotherapy, ECOG performance status (PS) 0-1. The primary endpoint was response rate, which was evaluated with RECIST. The planned sample size was 50 patients. We analyzed possible associations between these NSCLC marker levels and the efficacy of the CP regimen. Results: From April 2010 to June 2011, 50 N-sq NSCLC patients (male/female, 34/16; median age 60 y (28-74 y)) were enrolled in this study. Patients’ histological characteristics were: adeno/large/not otherwise specified (NOS), 39/5/6; PS: 0/1, 31/19. In these 50 patients, elevated levels of serum CYFRA, CEA, SCC and SLX were found in 25, 32, 5 and 32 patients, respectively. CYFRA was significantly associated with progression-free survival (PFS) (median PFS: 5.53 vs. 3.29 months; p < 0.05), whereas no significant associations were observed between PFS and CEA, SCC or SLX. In addition, multivariate analysis showed that higher CYFRA and PS levels were significant factors associated with a shorter PFS. (p < 0.05) Conclusions: Serum CYFRA is related to the outcome of CP treatment; our results suggest that serum CYFRA is a promising predictive marker of CP therapy.

1996 ◽  
Vol 82 (1) ◽  
pp. 57-60 ◽  
Author(s):  
Luciano Frontini ◽  
Paola Candido ◽  
Maria Teresa Cattaneo ◽  
Sabrina Zonato ◽  
Ernesto Piatto ◽  
...  

Aim The North Milan Group presents the results of a phase II study on a cisplatin-vinorelbine combination schedule in the treatment of locally advanced non-small cell lung cancer to evaluate its activity and tolerability. Methods Seventy-six consecutive patients entered the study. Patients’ characteristics were the following: males/females 69/7; median age, 61.4 years (range, 40-73); ECOG performance status, 0-1; 17 stage IIIa and 59 stage IIIb. There were 49 squamous cell carcinomas, 20 adenocarcinomas, and 7 large cell carcinomas. All patients had not been previously treated and showed measurable disease. Treatment consisted of vinorelbine, 25 mg/m2 on days 1 and 8, plus cisplatin, 80 mg/m2 on day 1, administered intravenously every 21 days for three standard courses. Results Seventy-four patients were evaluable for response. Objective responses were documented in 42/74 patients with an overall response rate (CR+PR) of 56.7%; 18/74 patients (24.3%) showed stable disease and the remaining 14/74 (18.9%) went into progression. Twelve patients (16.2%) were suitable for a subsequent surgery. The median duration of response was 13.3 months. Survival time ranged from 4 to 36 months: it was 14.6 months for PR patients, 8.6 months for NC and 5 months for PD. Mean survival time is presently 12.85 months (SE, 1.2 months). Toxicity evaluated on 222 cycles administered was acceptable, and it was necessary to use G-CSF or delay the treatment because of severe leukopenia in only a few cases. Conclusions The regimen is active and safe: the slight survival increase is likely due to the small amenability to surgery achieved (16.2%). However, our results are fully comparable to others obtained with vinorelbine in two/three drug combination chemotherapy regimens.


2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e21194-e21194
Author(s):  
James Newman ◽  
Chung-Shien Lee ◽  
Kerri McGovern ◽  
Nagashree Seetharamu

e21194 Background: Immune checkpoint inhibitors (ICIs) have transformed the standard of care of non-small cell lung cancer (NSCLC) and are capable of inducing a sustained response in a cohort of patients. For those who progress while on ICIs and do not have a targetable mutation, options are typically reduced to chemotherapeutic regimens which have a higher probability of toxicity. In patients with a suboptimal performance status or those who are opposed to receiving chemotherapy and are not eligible or interested in clinical trials, treatments are unfortunately limited. Patients who progress on one ICI do not receive a different ICI as part of standard care in subsequent lines of therapy. Data behind switching ICIs, particularly to those with a different mechanism of action (ie anti-PD-1 followed by anti-PD-L1 or vice versa), are lacking. We evaluated the efficacy of receiving a 2nd ICI in patients with NSCLC. Methods: A single-center, IRB-approved retrospective analysis was conducted of NSCLC patients treated with two different ICIs from March 2015 to July 2020. ICIs were given either in combination with chemotherapy or as monotherapy. Patient and tumoral characteristics, including PD-L1 status (if available) and sequence of ICIs, were captured. A positive PD-L1 was defined as PD-L1 expression > 0%. Progression-free survival (PFS) of each ICI (defined as PFS1 and PFS2) were calculated in months (m) for each patient. Median PFS2 was compared between groups stratified by a cutoff median PFS1 of 3m, sequence of PD-1 and PD-L1 inhibitors, and PD-L1 positive and negative subsets. Mood’s median test was used to compare medians. Results: 26 patients were included in the final analysis. 19/26 patients had a PFS1 > 3m. For this cohort, the median PFS2 was 2.5m (Range: 0.1-36.2) compared to median PFS2 of 1.6m (Range: 0.6-15.9) in patients with PFS1 < 3m (p=0.1847). 15 patients received a PD-1 inhibitor followed by a PD-L1 inhibitor. In this subgroup, the median PFS2 was 1.2m (Range: 0.2-36.2). Alternatively, 7 patients received a PD-L1 inhibitor followed by a PD-1 inhibitor and the median PFS2 in this cohort was 2.3m (Range: 0.1-15.9) (p=0.6471). PD-L1 data was available for 19 patients. 8/19 patients with positive PD-L1 had a median PFS2 of 3.6m (Range: 0.2-13.3) compared to median PFS2 of 1.3m (Range: 0.1-36.2) in patients with negative PD-L1 (p=0.2599). Conclusions: Treatment with a 2nd ICI can potentially provide a modest benefit in patients with advanced NSCLC, and some may even experience a very prolonged response. PFS1, sequence of PD-1/PD-L1 inhibitors, and PD-L1 expression did not show any significant correlation with PFS2. Using a 2nd ICI should be considered for advanced NSCLC patients with diminished performance status or limited treatment options.


PRILOZI ◽  
2020 ◽  
Vol 41 (2) ◽  
pp. 29-36
Author(s):  
Simonida Crvenkova

AbstractSummary: Anaplastic lymphoma kinase (ALK) rearrangement is identified in approximately 3-7% of all metastatic non-small cell lung cancer (NSCLC) patients, and ALK tyrosine kinase inhibitors (TKIs) have revolutionized the management of this subset of lung cancer cases.Purpose: This study aims to show alectinib (TKI) effectiveness and safety with focus on alectinib intracranial efficacy for ALK+ NSCLC patients.Case presentation: Patient 1 was a 46-year-old woman diagnosed with non-small cell lung cancer with an echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase fusion gene (ALK+). She presented with intracranial and liver metastases and poor performance status of ECOG 3. Alectinib was initiated as a second line therapy, after whole brain irradiation and discontinuation of first line chemotherapy after two cycles, due to the central nervous system progression and liver metastases. Good response was consequently achieved, characterized with improved overall performance and without significant adverse events.Patient 2 was a 53-year old man with left sided lung adenocarcinoma surgically treated in 2017. Post-operative pTNM stage was IIB with a positive resection margin- R1. He received adjuvant chemotherapy and radiotherapy. In 2019, after two and half years of being disease free, he presented with severe cerebral symptoms leading to poor performance status. CT scan of the brain showed multiple brain metastases. He was treated with first line alectinib after completion of whole brain radiotherapy. In 5 months period he got significantly better and able for work again.Conclusions: We recommend alectinib as a first and second line treatment approach for ALK+ NSCLC patients, in particular the ones with brain metastases at the time of diagnosis and poor PS.


2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e21651-e21651
Author(s):  
Alfredo Addeo ◽  
Giulio Metro ◽  
Diego Signorelli ◽  
Panagiota Economopoulou ◽  
Fausto Roila ◽  
...  

e21651 Background: We retrospectively analysed real-world clinical outcomes of patients with advanced non-small-cell lung cancer (NSCLC) harbouring high PD-L1 expression ( > 50%) and treated with first-line pembrolizumab, following the Keynote 024 regimen. In the recent PePS2 trial and Checkmate 817, we see that some patients with PS2 could benefit from a durable response to checkpoint inhibitors. However, current data does not suggest an improvement in median OS compared to historical data on chemotherapy in this setting. Methods: Data was collected by 16 participating centers. The trial was approved by local ethics committees and patients included signed a general consent form. All patients with NSCLC with PD-L1 expression ≥50%, treated with first-line pembrolizumab were included, from the introduction of first-line pembrolizumab to the present. We collected medical data from patient files, pathology reports and laboratory reports for all patients. Patient characteristics, comorbidities, Eastern Cooperative Oncology Group (ECOG) performance status (PS), and tumor characteristics were reported. Overall survival (OS) was calculated from the date of the first cycle of pembrolizumab to death and estimated through the Kaplan-Meier method. Results: 302 patients were identified, of which 247 with a PS of 0-1, 52 with a PS of 2. Patients (3) with PS3 were excluded. The median age was 69 with a range from 19 to 87 years. There were 193 males and 106 females, 90% were active or former smokers, 19% had brain lesions at diagnosis. Only 14% received brain radiotherapy. Median OS was 7.2 months among patients with PS2, while not reached for those with PS0-1 (HR 3.80, 95% confidence interval 2.49-5.78). Conclusions: Patients with a PS of 2 had significantly worse survival than those with PS0-1. The retrospective nature of our trial and lack of a control arm treated with chemotherapy do not allow us to postulate as to whether PS is predictive or prognostic. Our data suggests worse survival among NSCLC patients with PS2 treated with front-line pembrolizumab. A prospective randomized trial comparing immunotherapy to chemotherapy or chemo-immunotherapy in this population would be welcome.


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