Time-dependent efficacy of checkpoint inhibitor nivolumab in metastatic lung cancer patients.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 9096-9096
Author(s):  
Abdoulaye Karaboué ◽  
Thierry Collon ◽  
Ida Pavese ◽  
Viviane Bodiguel ◽  
Elda Zakine ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Single Agent ◽  
Progression Free Survival ◽  
Time Dependent ◽  
Cd8 Cells ◽  
Lung Cancer Patients ◽  
Stage 4 ◽  
Metastatic Lung ◽  
Grade 3 ◽  
Metastatic Sites

9096 Background: Nivolumab (NIV) is a Programmed-cell-Death-1 inhibitor approved as 2nd line treatment for metastatic Non-Small Cell Lung Cancer (NSCLC). NIV mainly targets T(CD8) cells, whose functions and trafficking are regulated by circadian clocks (Nobis et al. PNAS 2019), hence suggesting possible dosing time-dependent changes in NIV efficacy. Methods: Consecutive metastatic NSCLC patients (pts) received single agent NIV (240 mg iv q 2 weeks) at a single institution. NIV timing slots were randomly allocated for each course by the day hospital coordinator on a logistics basis and recorded. The median NIV timing and its intra-pt coefficient of variation (CVar) were computed over the whole treatment span. The study population was split into two NIV timing groups based upon the median value of the median treatment times of all the pts. CTCAE-toxicity rates were compared between groups with c2 or Fisher exact. Progression free survival (PFS) and overall survival (OS) were compared between both NIV timing groups with Log Rank. Results: From 9/2015 to 11/2020, the study accrued 95 stage 4 NSCLC pts (males, 83%; PS 0-1, 96%), aged 41-83 years (median, 67). Primary histological types were adenocarcinoma (55 pts, 58%), squamous cell carcinoma (37 pts, 39%) or unspecified (3 pts, 3%). The pts had a median of 4 metastatic sites, including bone (52% of the pts), pleura (41%), liver (25%), brain (24%) and adrenal gland (20%). A total of 1818 NIV courses were given as 2nd line for 72 pts (76%), or as 3rd or later line for 22 pts (23%). Median PFS and OS (months, mo.) were 3.9 mo. [95% CL, 2.1 – 5.8], and 14.0 mo. [9.5 – 18.4] respectively, for the 95 pts. The majority of NIV administrations occurred between 9:27 and 12:54 for 48 pts (‘morning’ group) and between 12:55 and 17:14 for 47 pts (‘afternoon’ group), with intra-pt NIV timing CVar ranging from 2% to 21% (median, 10%). Main pts characteristics were similar for both groups, except for fewer females (8% vs 26%) and younger age (median, 66 vs 69 years) in the ‘morning’ group compared to the ‘afternoon’ one. Grade 3-4 fatigue, anorexia or myalgias were less in the ‘morning’ group compared with the “afternoon’ one (6% vs 15%; 2% vs 6%; 0% vs 4%, respectively). Strikingly, median PFS [95% CI] were 11.3 mo. [5.5 - 17.1] for the ‘morning’ group as compared to 3.1 mo. [1.5 - 4.6] for the ‘afternoon’ one (p<0.001). Median OS were 34.2 mo. [15.1 - 53.3] for the ‘morning’ group vs 9.6 mo. [4.9 - 14.4] for the ‘afternoon’ group (p<0.001). Multivariate analyses identified NIV ‘morning’ timing and 2nd line administration, as significant independent predictors of longer PFS and OS. Conclusions: NIV was both less toxic and four times as effective following ‘morning’ as compared to ‘afternoon’ dosing in this study in Stage 4 NSCLC pts, possibly as a result of dosing time-dependent pharmacology. Translational and clinical nivolumab timing validation studies are needed, in order to optimize pts benefits from cancer immunotherapy.

scholarly journals Treatment of Rare Mutations in Patients with Lung Cancer

Biomedicines ◽  
2021 ◽  
Vol 9 (5) ◽  
pp. 534
Author(s):  
Tarek Taha ◽  
Rasha Khoury ◽  
Ronen Brenner ◽  
Haitam Nasrallah ◽  
Irena Shofaniyeh ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Treatment Options ◽  
Progression Free Survival ◽  
Lung Cancer Patients ◽  
Raf Kinase ◽  
Rare Mutations ◽  
Epidermal Growth ◽  
Mesenchymal Epithelial Transition Factor ◽  
Metastatic Sites ◽  
Pharmaceutical Agents

Lung cancer is a worldwide prevalent malignancy. This disease has a low survival rate due to diagnosis at a late stage challenged by the involvement of metastatic sites. Non-small-cell lung cancer (NSCLC) is presented in 85% of cases. The last decade has experienced substantial advancements in scientific research, leading to a novel targeted therapeutic approach. The newly developed pharmaceutical agents are aimed towards specific mutations, detected in individual patients inflicted by lung cancer. These drugs have longer and improved response rates compared to traditional chemotherapy. Recent studies were able to identify rare mutations found in pulmonary tumors. Among the gene alterations detected were mesenchymal epithelial transition factor (MET), human epidermal growth factor 2 (HER2), B-type Raf kinase (BRAF), c-ROS proto-oncogene (ROS1), rearranged during transfection (RET) and neurotrophic tyrosine kinase (NTRK). Ongoing clinical trials are gaining insight onto possible first and second lines of medical treatment options intended to enable progression-free survival to lung cancer patients.

Correlation between PD-L1 level and immunotherapy outcome in NSCLC in Lebanon, 2012-2018: A multicenter observational review.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e20524-e20524
Author(s):  
Ahmad Ghoche ◽  
Lewis Nasr ◽  
Saada Diab ◽  
Fadi Nasr
Keyword(s):  
Lung Cancer ◽  
Overall Survival ◽  
Objective Response ◽  
Stage Iv ◽  
Progression Free Survival ◽  
Free Survival ◽  
Lung Cancer Patients ◽  
Checkpoint Pathway ◽  
Grade 3 ◽  
Line Of Therapy

e20524 Background: Immunotherapy targeting the PD1/PDL1 checkpoint pathway represents an important innovation in lung cancer treatment. In our research, we evaluate the correlation of PD-L1 expression with clinical outcomes (progression free survival, overall survival, objective response rate) in lung cancer patients in 4 centers in Lebanon. Methods: The 57 patients enrolled in this observational study were stage IIIB/IV NSCLC and SCLC who received immunotherapy with nivolumab, pembrolizumab or atezolizumab at any line of treatment, and were recruited between February 2012 and august 2018. Immunotherapy was continued until progression, death or unacceptable toxicity. PD-L1 expression was assessed on tumor samples either on diagnosis or at progression. Patients were divided into 3 categories according to PD-L1 level (< 1, 1-49, > 50%). Progression free survival defines the time from randomization to disease progression after each line of therapy. Overall survival defines time from randomization to death from any cause. Results: 70.18% had adenocarcinoma, 26.32% had squamous cell carcinoma, 1.75% had small cell lung cancer and one pathology was missing from the file. 66.66% were stage IV at diagnosis, 26.31% were stage 3. PD-L1 expression was > 50% in 40.35% of patients, 24.56% had a level between 1 and 50% and the remaining had a value of less than 1%. PD-L1 was missing or not done in 15.79%. Median PFS was 13.9 months. Median OS was 14.2 months. 22.81% received immunotherapy as first line and 75% of the remaining patients upon first progression. PFS1 was 4.2 months. Mean time to first progression on immunotherapy was 3.6 months in patients with PD-L1 > 50%, 10.5 months in PD-L1 between 1 and 50% and 14.3 months in those who had PD-L1 < 1%. At the date of data cutoff, 49.12 % of patients were still receiving immunotherapy. No grade 3 or 4 immune related adverse events were seen during follow-up. Conclusions: The efficacy and safety of anti-PD-1 medications for advanced NSCLC were comparable in real-world and clinical settings. Prediction of treatment response from tumor PD-L1 expression seemed less practical than that was expected

Safety and efficacy of single-agent lenalidomide in patients with relapsed and refractory multiple myeloma

Blood ◽  
2009 ◽  
Vol 114 (4) ◽  
pp. 772-778 ◽  
Author(s):  
Paul Richardson ◽  
Sundar Jagannath ◽  
Mohamad Hussein ◽  
James Berenson ◽  
Seema Singhal ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Single Agent ◽  
Progression Free Survival ◽  
Prior Treatment ◽  
Once Daily ◽  
Free Survival ◽  
Refractory Multiple Myeloma ◽  
Treatment Regimens ◽  
Common Grade ◽  
Grade 3

Abstract Lenalidomide plus dexamethasone is effective for the treatment of relapsed and refractory multiple myeloma (MM); however, toxicities from dexamethasone can be dose limiting. We evaluated the efficacy and safety of lenalidomide monotherapy in patients with relapsed and refractory MM. Patients (N = 222) received lenalidomide 30 mg/day once daily (days 1-21 every 28 days) until disease progression or intolerance. Response, progression-free survival (PFS), overall survival (OS), time to progression (TTP), and safety were assessed. Overall, 67% of patients had received 3 or more prior treatment regimens. Partial response or better was reported in 26% of patients, with minimal response 18%. There was no difference between patients who had received 2 or fewer versus 3 or more prior treatment regimens (45% vs 44%, respectively). Median values for TTP, PFS, and OS were 5.2, 4.9, and 23.2 months, respectively. The most common grade 3 or 4 adverse events were neutropenia (60%), thrombocytopenia (39%), and anemia (20%), which proved manageable with dose reduction. Grade 3 or 4 febrile neutropenia occurred in 4% of patients. Lenalidomide monotherapy is active in relapsed and refractory MM with acceptable toxicities. These data support treatment with single-agent lenalidomide, as well as its use in steroid-sparing combination approaches. The study is registered at http://www.clinicaltrials.gov as NCT00065351.

scholarly journals Phase II Trial of Cetuximab With or Without Paclitaxel in Patients With Advanced Urothelial Tract Carcinoma

2012 ◽  
Vol 30 (28) ◽  
pp. 3545-3551 ◽  
Author(s):  
Yu-Ning Wong ◽  
Samuel Litwin ◽  
David Vaughn ◽  
Seth Cohen ◽  
Elizabeth R. Plimack ◽  
...  
Keyword(s):  
Phase Ii ◽  
Urothelial Cancer ◽  
Single Agent ◽  
Progression Free Survival ◽  
Salvage Chemotherapy ◽  
Free Survival ◽  
Metastatic Urothelial Cancer ◽  
Metastatic Setting ◽  
Previously Treated ◽  
Grade 3

Purpose The benefit of salvage chemotherapy is modest in metastatic urothelial cancer. We conducted a randomized, noncomparative phase II study to measure the efficacy of cetuximab with or without paclitaxel in patients with previously treated urothelial cancer. Patients and Methods Patients with metastatic urothelial cancer who received one line of chemotherapy in the perioperative or metastatic setting were randomly assigned to 4-week cycles of cetuximab 250 mg/m2 with or without paclitaxel 80 mg/m2 per week. We used early progression as an indicator of futility. Either arm would close if seven of the initial 15 patients in that arm progressed at the first disease evaluation at 8 weeks. Results We enrolled 39 evaluable patients. The single-agent cetuximab arm closed after nine of the first 11 patients progressed by 8 weeks. The combination arm completed the full accrual of 28 patients, of whom 22 patients (78.5%) had visceral disease. Twelve of 28 patients had progression-free survival greater than 16 weeks. The overall response rate was 25% (95% CI, 11% to 45%; three complete responses and four partial responses). The median progression-free survival was 16.4 weeks (95% CI, 12 to 25.1 weeks), and the median overall survival was 42 weeks (95% CI, 30.4 to 78 weeks). Treatment-related grade 3 and 4 adverse events that occurred in at least two patients were rash (six cases), fatigue (five cases), and low magnesium (three cases). Conclusion Although it had limited activity as a single agent, cetuximab appears to augment the antitumor activity of paclitaxel in previously treated urothelial cancers. The cetuximab and paclitaxel combination merits additional study to establish its role in the treatment of urothelial cancers.

EGFR TKI Combined with PD1 Inhibitor for EGFR Mutated Lung Cancer with Breast Metastasis

2021 ◽  
Author(s):  
Xuyu Gu ◽  
Chanchan Gao ◽  
Longfei Wang ◽  
Shiya Zheng
Keyword(s):  
Lung Cancer ◽  
Lung Adenocarcinoma ◽  
Left Breast ◽  
Axillary Lymph ◽  
Breast Metastasis ◽  
Lung Cancer Patients ◽  
Metastatic Lung ◽  
New Ideas ◽  
Recurrent Pleural Effusion ◽  
Egfr Tki

Abstract Background: Lung adenocarcinoma with breast metastasis is rare. In the present study, a case of an advanced patient with breast metastasis from lung adenocarcinoma with EGFR 21 exon p.L858R mutation who underwent EGFR TKI combined with PD1 inhibitor is reported.Case presentation: A 62-year-old female patient diagnosed with lung adenocarcinoma who had undergone six times disease progress and breast metastasis in fifth-time disease progress.The patient underwent left breast puncture and axillary lymph node in ultrasound-guided and the postoperative pathological diagnosis of metastatic lung adenocarcinoma was confirmed. And then gene detection showed EGFR 21 exon p.L858R mutation. Breast metastasis from lung adenocarcinoma was diagnosed and the patient is being treated with Almonertinib combined with PD1 inhibitor.Conclusion: Breast metastasis is rare and lung adenocarcinoma might be the primary disease. Gene indection is important. And for lung cancer patients with recurrent pleural effusion, visit of the breast should be included in the follow-up process. In addition, the treatment model of interspersed immunotherapy after EGFR resistance has brought new ideas for the treatment of lung cancer with breast metastasis.

Pretreatment lung immune prognostic index as biomarker in advanced non-small-cell lung cancer patients receiving first line pembrolizumab

Immunotherapy ◽  
2021 ◽  
Author(s):  
Antonello Veccia ◽  
Vincenzo Sforza ◽  
Emanuela Vattemi ◽  
Alessandro Inno ◽  
Stefania Kinspergher ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cancer Patients ◽  
Cell Lung Cancer ◽  
Prognostic Index ◽  
Progression Free Survival ◽  
Small Cell ◽  
Small Cell Lung ◽  
Lung Cancer Patients ◽  
C Statistic

Background: To investigate the role of pretreatment lung immune prognostic index (LIPI) as biomarker in PD-L1 ≥50% non-small-cell lung cancer patients receiving pembrolizumab. Patients & methods: We retrospectively identified 117 patients, divided into 3 prognostic groups according to LIPI score. For each patient, we evaluated 1-year overall survival (OS) and progression-free survival rate. C-statistic and survival receiver operating characteristic curves were used to study discrimination of LIPI. Results: After a median follow-up of 11.7 months, 1-year OS rate was 60.1%, 35.3% and 28.6%, while 1-year progression-free survival rate was 39.1%, 20.6% and 14.3% in good, intermediate and poor LIPI groups, respectively (p < 0.001). The c-statistic and area under the curve of LIPI were 0.63 and 0.662 for OS and 1-year OS, respectively. Conclusions: Higher LIPI score is related to worse survival in advanced non-small-cell lung cancer patients treated with first-line pembrolizumab. However, based on c-statistic and area under the curve, LIPI does not represent a good prognostic survival model.

GEIS 39: Phase II trial of nabpaclitaxel for the treatment of patient with multiply relapsed/refractory desmoplastic small round cell tumor (DSRCT) and Ewing sarcoma (EwS).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 11529-11529
Author(s):  
Jaume Mora ◽  
Mariona Suñol ◽  
Nadia Hindi ◽  
Alicia Castañeda ◽  
Andrés Redondo ◽  
...  
Keyword(s):  
Single Agent ◽  
Progression Free Survival ◽  
Predictive Biomarker ◽  
Free Survival ◽  
Pediatric Solid Tumors ◽  
Meaningful Activity ◽  
Common Grade ◽  
Central Pathology ◽  
Grade 3 ◽  
Further Development

11529 Background: Nab-paclitaxel (albumin-bound paclitaxel) has shown preclinical activity against pediatric solid tumors. Preclinical data in EwS PDX models suggested high activity of nab-paclitaxel in tumors expressing high-levels of SPARC. Tumoral SPARC facilitates the accumulation of albumin in the tumor and increases the effectiveness of albumin-bound paclitaxel. Nab-paclitaxel utilizes albumin to deliver paclitaxel via caveolin-mediated endocytosis which is expressed in the EwS cells surface. We hypothesized that SPARC can be a predictive biomarker for nab-paclitaxel in EwS and DSRCT that could potentially be relevant for a better design of clinical trials and personalized treatments using nab-paclitaxel. Methods: Main endpoint of GEIS-39 was the overall response rate (ORR) assessed by RECIST 1.1 criteria with centralized pathology and imaging review. Secondary objectives included safety according to the CTCAE 4.0 criteria. Patients aged ≥ 6 months and ≤ 40 years, with relapsed/refractory DSRCT were eligible after having received at least one previous poly-chemotherapy line; EwS must have received at least two standard chemotherapy lines. Prior taxane therapy was accepted. Central pathology review selected for tumors with > Grade 3 (intense and diffuse) expression of SPARC by immunohistochemistry to be eligible. Nab-paclitaxel was administered as follows: age ≥ 21 and ≤ 40 years: 125 mg/m2 days 1, 8 and 15 in cycles of 28 days; age ≥ 6 months and ≤ 20 years: 240 mg/m2 days 1, 8 and 15 in cycles of 28 days. A 30% ORR was anticipated with a sample size of 25 patients needed to test the hypothesis. Stopping rule was set at 1 response within the first 16 treated pts. If 5 or more successes were observed in 25 pts, the results of the trial will warrant further investigation. Results: Twenty-nine patients were enrolled from June 2017 until October 2019, 11 DSRCT and 18 EwS. Median age was 32 years (range 14-69), and 5 females and 24 males were included, having received a median of 3 previous systemic treatment lines. Patients received a median of 3 cycles of nab-paclitaxel (range 1-17). In the EwS cohort an ORR of 33.3% (all partial responses, median duration 2 months) and 16.7% of stabilizations were achieved. No objective responses were observed among DSRCT pts, but 27.3% of pts achieved a stabilization. Overall, median progression free survival was 2.8 months and median overall survival 12.1 months, with no significant differences between DSRCT and EwS cohorts. Most common grade 3 toxicities were neutropenia (20.7%) and diarrhea (10.3%). Conclusions: Single agent nab-paclitaxel in biomarker selected EwS patients, but not in DSRCT, provided clinically meaningful activity that deserves further development. Nab-paclitaxel had a manageable adverse event profile. Clinical trial information: 2016-002464-14.

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