scholarly journals Efficacy of S-1 after pemetrexed in patients with non-small cell lung carcinoma: a retrospective multi-institutional analysis

2021 ◽  
Author(s):  
Shinnosuke Takemoto ◽  
Kazumasa Akagi ◽  
Sawana Ono ◽  
Hiromi Tomono ◽  
Noritaka Honda ◽  
...  
Keyword(s):  
Overall Response Rate ◽  
Response Rate ◽  
Small Cell Lung Carcinoma ◽  
Progression Free Survival ◽  
Small Cell Lung ◽  
Confidential Interval ◽  
Cell Lung Carcinoma ◽  
Free Survival ◽  
Time To Treatment Failure ◽  
Nsclc Patients

Abstract Background: This study was designed to evaluate the treatment effect of S-1 following PEM-containing treatment. Methods: This retrospective study included patients with advanced (c-stage III or IV, UICC 7th) or recurrent NSCLC who received S-1 monotherapy following the failure of previous PEM-containing chemotherapy at 6 hospitals in Japan. Primary endpoint: Overall response rate (ORR). Secondary endpoint: Disease control rate (DCR), time to treatment failure (TTF), progression-free survival (PFS), and overall survival (OS). Results: A total of 53 NSCLC patients met the criteria. Forty-six patients had adenocarcinoma (88.7%) and no patients had squamous cell carcinoma. Thirty-one patients (58.5%) received the standard S-1 regimen and 18 patients (34.0%) received the modified S-1 regimen. ORR was 1.9% (95% confidential interval (CI): 0.00-10.1%). Median TTF, PFS, and OS were 65 days, 84 days, and 385 days, respectively. Conclusion: Although there were several limitations in this study, the ORR of S-1 after PEM in patients with non-SQ NSCLC was low compared to the historical control. It might be one of the choices to avoid S-1 treatment in PEM-treated patients who need tumor shrinkage.

scholarly journals Efficacy of S-1 after Pemetrexed in Patients with Non-small Cell Carcinoma: A Retrospective Multi-institutional Analysis

2020 ◽  
Author(s):  
Shinnosuke Takemoto ◽  
Kazumasa Akagi ◽  
Sawana Ono ◽  
Hiromi Tomono ◽  
Noritaka Honda ◽  
...  
Keyword(s):  
Cell Carcinoma ◽  
Overall Response Rate ◽  
Response Rate ◽  
Progression Free Survival ◽  
Small Cell ◽  
Confidential Interval ◽  
Free Survival ◽  
Time To Treatment Failure ◽  
Back Ground ◽  
Nsclc Patients

Abstract Back ground: This study was designed to evaluate the treatment effect of S-1 following PEM-containing treatment. Methods: This retrospective study included patients with advanced (c-stage III or IV, UICC 7th) or recurrent NSCLC who received S-1 monotherapy following the failure of previous PEM-containing chemotherapy at 6 hospitals in Japan. Primary endpoint: Overall response rate (ORR). Secondary endpoint: Disease control rate (DCR), time to treatment failure (TTF), progression-free survival (PFS), and overall survival (OS). Results: A total of 53 NSCLC patients met the criteria. Forty-six patients had adenocarcinoma (88.7%) and no patients had squamous cell carcinoma. Thirty-one patients (58.5%) received the standard S-1 regimen and 18 patients (34.0%) received the modified S-1 regimen. ORR was 1.9% (95% confidential interval (CI): 0.00-10.1%). Median TTF, PFS, and OS were 65 days, 84 days, and 385 days, respectively. Conclusion: Although there were several limitations in this study, the ORR of S-1 after PEM in patients with non-SQ NSCLC was low compared to the historical control. It might be one of the choices to avoid S-1 treatment in PEM-treated patients who need tumor shrinkage.

scholarly journals Current Management of Oligometastatic Lung Cancer and Future Perspectives: Results of Thermal Ablation as a Local Ablative Therapy

Cancers ◽  
2021 ◽  
Vol 13 (20) ◽  
pp. 5202
Author(s):  
Mario Ghosn ◽  
Stephen B. Solomon
Keyword(s):  
Thermal Ablation ◽  
Kinase Inhibitors ◽  
Small Cell Lung Carcinoma ◽  
Progression Free Survival ◽  
Cell Lung Carcinoma ◽  
Free Survival ◽  
Key Factor ◽  
Patient Selection Criteria ◽  
Nsclc Patients

A growing body of evidence shows improved overall survival and progression-free survival after thermal ablation in non-small cell lung carcinoma (NSCLC) patients with a limited number of metastases, combined with chemotherapy or tyrosine kinase inhibitors or after local recurrence. Radiofrequency ablation and microwave ablation are the most evaluated modalities, and target tumor size <3 cm (and preferably <2 cm) is a key factor of technical success and efficacy. Although thermal ablation offers some advantages over surgery and radiotherapy in terms of repeatability, safety, and quality of life, optimal management of these patients requires a multidisciplinary approach, and further randomized controlled trials are required to help refine patient selection criteria. In this article, we present a comprehensive review of available thermal ablation modalities and recent results supporting their use in oligometastatic and oligoprogressive NSCLC disease along with their potential future implications in the emerging field of immunotherapy.

scholarly journals Overall Response Rate, Progression-Free Survival, and Overall Survival With Targeted and Standard Therapies in Advanced Non–Small-Cell Lung Cancer: US Food and Drug Administration Trial-Level and Patient-Level Analyses

2015 ◽  
Vol 33 (9) ◽  
pp. 1008-1014 ◽  
Author(s):  
Gideon M. Blumenthal ◽  
Stella W. Karuri ◽  
Hui Zhang ◽  
Lijun Zhang ◽  
Sean Khozin ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Overall Response Rate ◽  
Advanced Nsclc ◽  
Response Rate ◽  
Progression Free Survival ◽  
Small Cell ◽  
Small Cell Lung ◽  
Free Survival ◽  
Patient Level ◽  
Level Analysis

Purpose To conduct analyses exploring trial-level and patient-level associations between overall response rate (ORR), progression-free survival (PFS), and overall survival (OS) in advanced non–small-cell lung cancer (NSCLC) trials. Methods We identified 14 trials (N = 12,567) submitted to US Food and Drug Administration since 2003 of treatments for advanced NSCLC. Only randomized, active-controlled trials with more than 150 patients were included. Associations between trial-level PFS hazard ratio (HR), OS HR, and ORR odds ratio were analyzed using a weighted linear regression model. Patient-level responder analyses comparing PFS and OS between patients with and without an objective response were performed using pooled data from all studies. Results In the trial-level analysis, the association between PFS and ORR was strong (R2 = 0.89; 95% CI, 0.80 to 0.98). There was no association between OS and ORR (R2 = 0.09; 95% CI, 0 to 0.33) and OS and PFS (R2 = 0.08; 95% CI, 0 to 0.31). In the patient-level responder analyses, patients who achieved a response had better PFS and OS compared with nonresponders (PFS: HR, 0.40; 95% CI, 0.38 to 0.42; OS: HR, 0.40; 95% CI, 0.38 to 0.43). Conclusion On a trial level, there is a strong association between ORR and PFS. An association between ORR and OS and between PFS and OS was not established, possibly because of cross-over and longer survival after progression in the targeted therapy and first-line trials. The patient-level analysis showed that responders have a better PFS and OS compared with nonresponders. A therapy in advanced NSCLC with a large magnitude of effect on ORR may have a large PFS effect.

Neurotoxicity associated with anti-PD1 therapy: A multi-center case series.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e21641-e21641 ◽  
Author(s):  
Jess Louise Smith ◽  
Alexander M. Menzies ◽  
Justine Vanessa Cohen ◽  
Margarida Mut Lioret ◽  
Alpaslan Ozgun ◽  
...  
Keyword(s):  
Nervous System ◽  
Overall Response Rate ◽  
Treatment Initiation ◽  
Response Rate ◽  
Case Series ◽  
Progression Free Survival ◽  
High Response Rate ◽  
Small Cell Lung ◽  
Free Survival ◽  
Median Progression Free Survival

e21641 Background: The anti-PD1 antibodies (PD1) pembrolizumab and nivolumab are now FDA-approved in multiple malignancies. With increased use, rarer immune-related adverse events (irAEs) not well characterized in clinical trials are being identified, including neurotoxicities. Methods: Patients (Pts) who developed neurotoxicites while being treated with PD1 (alone or in combination) were retrospectively identified from 10 cancer centers. Data regarding treatment, toxicity and outcome were examined. Results: 40 pts (38 melanoma and 2 non-small cell lung cancer pts) developed neurotoxicity; 14 on anti-PD1 monotherapy, 23 in combination or sequence with ipilimumab, and 3 on blinded trials or in combination with interferon. The overall response rate was 90% and median progression free survival was not reached. The median time from treatment initiation to development of neurotoxicity was 7 weeks (range 1-86.5 weeks). 8 pts had died, 5 from disease progression and, 2 from neurotoxicity. 26 pts (65%) developed other irAEs. 27 (67.5%) pts developed toxicities affecting the peripheral nervous system including motor sensory neuropathies (6), sensory neuropathies (4), and Myasthenia Gravis (3). 13 (32.5%) pts developed central nervous system toxicities including aseptic meningitis (6) and encephalitis (4). 24 (60%) pts were treated with steroids alone. 9 pts required further immunomodulation including IVIG (7), plasmapheresis (3), MMF (1) and rituximab (1). 17 (43%) had complete resolution of symptoms, 5 (13%) had stable or worsening neurological disease, and 22 ( 55%) were improving at the time of datacut . 10 pts were retreated with PD1, of which 2 developed exacerbation of prior neurological symptoms. Conclusions: While rare, a variety of neurotoxicities can occur with PD1 treatment. Management may require immunomodulation beyond corticosteroids. Given the high response rate observed in this cohort, such toxicities and their management do not appear to negatively impact treatment response.

246 Clinicopathologic and genomic correlates of tumor mutational burden and its impact on PD-(L)1 inhibition efficacy in non-small cell lung cancer according to different PD-L1 expression subgroups

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A266-A267
Author(s):  
Biagio Ricciuti ◽  
Navin Mahadevan ◽  
Renato Umeton ◽  
Joao Alessi ◽  
Andrew Polio ◽  
...  
Keyword(s):  
Overall Survival ◽  
Overall Response Rate ◽  
Response Rate ◽  
Recursive Partitioning ◽  
Progression Free Survival ◽  
Small Cell Lung ◽  
Free Survival ◽  
Overall Response ◽  
Mutational Burden ◽  
Tumor Mutational Burden

BackgroundHigh tumor mutational burden (TMB) and PD-L1 expression are associated with improved clinical outcomes in patients (pts) with non-small cell lung cancer (NSCLC) treated with immune checkpoint inhibitors (ICIs). However, how TMB performs as a predictive biomarker to ICIs in different PD-L1 expression subgroups is not well characterized.MethodsWe collected clinicopathologic and genomic data from NSCLCs which underwent targeted NGS and TMB assessment at DFCI. An unbiased recursive partitioning (URP) algorithm was used to investigate an optimal TMB cut-off with respect to objective response rate (ORR) in the subset of pts treated with ICIs. This TMB cut-off was then validated in the prospective POPLAR/OAK cohort.ResultsAmong 3560 NSCLCs identified, median TMB was significantly higher among current smokers compared to former (P<0.0001) and never smokers (P<0.0001), and there was a significant correlation between TMB and pack-years (figure 1A-B). Pts with BRAF or KRAS mutations had the highest median TMB (10.9 and 9.8 mutations/Megabase [mut/Mb], respectively), while tumors with RET and ALK alterations had the lowest median TMB of 5.3 mut/Mb (figure 2A-B). Tumors with PD-L1 expression of ≥50% had significantly higher median TMB compared to those with a PD-L1 expression of 1–49% (P=0.002) and <1% (P<00001). Among pts treated with ICIs (N=690), URP identified an optimal grouping TMB cut-off for ORR of 19.0 mut/Mb, which corresponded to the 90th percentile. Pts with a TMB of ≥19.0 mut/Mb had a significantly higher ORR (45.2% vs 20.1%, P<0.0001) and longer median PFS (11.0 vs. 2.9 months, HR:0.49, P<0.0001) and OS (20.8 vs. 11.2 months, HR:0.59, P=0.001) compared to those with a TMB of <19.0 mut/Mb (figure 3A-C). A TMB of ≥19.0 mut/Mb was an independent predictor of improved PFS and OS at multivariable analysis (table 1). A TMB within the top 10th percentile was confirmed to correlate with improved ORR and PFS in atezolizumab arm but not in the docetaxel arm of the POPLAR/OAK trials (figure 4A-B). When TMB and PD-L1 where integrated in the URP, we identified an optimal cut-off of 19 mut/Mb among cases with a PD-L1 expression of ≤25%, and of 8.4 mut/Mb among those with a PD-L1 expression of >25%, suggesting that TMB differentially impacts response to immunotherapy among PD-L1 high versus low NSCLCs (figure 5).Abstract 246 Figure 1(A) Correlation between TMB and smoking status. (B) Linear correlation between TMB and pack-years on a continuous scaleAbstract 246 Figure 2(A) TMB distribution across genomically defined subsets of NSCLC. (B) Pairwise comparison in TMB distribution among genomically defined subsets of NSCLC. Reported in each box are the Q-values for each comparison (FDR method of Benjamini and Hochberg)Abstract 246 Figure 3(A) Overall response rate, (B) progression-free survival and (C) overall survival to PD-(L)1 inhibition in patients with NSCLC and a TMB of ≥19.0 vs <19.0 mut/Mb, as determined by unbiased recursive partitioningAbstract 246 Figure 4(A) Overall response rate, progression-free survival and overall survival to atezolizumab in patients enrolled in the POPLAR/OAK trials and a bTMB of ≥25 (top 10th percentile) vs <25.0 (lower 90th percentile) mut/Mb. (B) Overall response rate, progression-free survival and overall survival to docetaxel in patients enrolled in the POPLAR/OAK trials and a bTMB of ≥25 (top 10th percentile) vs <25.0 (lower 90th percentile) mut/Mb. bTMB, blood tumor mutational burdenAbstract 246 Figure 5Unbiased regression tree algorithm recursively identifies that different TMB cut-offs impact response to immunotherapy in PD-L1 TPS high (≥25) vs low (<25%) NSCLCs. TPS, tumor proportion scoreAbstract 246 Table 1Multivariable Cox regression for PFS and OS among patients with NSCLC treated with PD-(L)1 blockade.ConclusionsThe impact of TMB may vary across PD-L1 expression subgroups. Rational integration of TMB and PD-L1 expression may identify NSCLCs with the greatest likelihood of response or resistance to ICIs.Ethics ApprovalClinicopathologic data were collected from patients with advanced NSCLC who had consented to a correlative research study (DF/HCC protocol #02-180).

Two schedules of teniposide with or without cisplatin in advanced non-small-cell lung cancer: a randomized study of the European Organization for Research and Treatment of Cancer Lung Cancer Cooperative Group.

1996 ◽  
Vol 14 (1) ◽  
pp. 127-134 ◽  
Author(s):  
T A Splinter ◽  
T Sahmoud ◽  
J Festen ◽  
N van Zandwijk ◽  
S Sörenson ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Side Effects ◽  
Response Rate ◽  
Progression Free Survival ◽  
Small Cell ◽  
Survival Duration ◽  
Small Cell Lung ◽  
Free Survival ◽  
Nsclc Patients ◽  
Survival Interval

PURPOSE We conducted a randomized trial to investigate the value of the addition of cisplatin to teniposide (VM26) and to investigate the schedule dependence of the topoisomerase II inhibitor VM26, in advanced non-small-cell lung cancer (NSCLC) patients. PATIENTS AND METHODS Two hundred twenty-five NSCLC patients were randomized to receive VM26 120 mg/m2 on days 1, 3, and 5 or 360 mg/m2 on day 1 only, either as a single drug or in combination with cisplatin 80 mg/m2 on day 1. Cycles were repeated every 3 weeks. Response rates, side effects, and survival were compared according to the 2 x 2 factorial design of this study. RESULTS The response rate of the two cisplatin-containing arms was superior to that of the two arms that contained VM26 only (22% v 6%, P < .001); progression-free survival and survival times were also longer in the cisplatin-containing arms (median, 4.3 v 2.2 months, P = .003; median 7.2 v 5.9 months, P = .008, respectively). Toxicity was significantly higher in the cisplatin-containing arms; the most frequent side effects were leukopenia, nausea and vomiting, and alopecia. The schedule of VM26 did not significantly influence the response rate, progression-free survival interval, or survival duration. However, the response rate of the 1-day administration was significantly lower than that of the 3-day administration when given as single drugs. CONCLUSION The addition of cisplatin to VM26 improves the response rate, progression-free survival interval, and survival duration over VM26 alone, although at the cost of a significant increase in toxicity. Cisplatin should be considered as the basis for combination chemotherapies in advanced NSCLC.

Overweight or obese patients may take longer to respond and be less responsive to immune checkpoint inhibitors in non-small cell lung cancer: A retrospective review.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e21209-e21209
Author(s):  
John P. Palmer ◽  
Yenong Cao ◽  
Samer Ibrahim ◽  
Natasha Dhawan ◽  
Muhammad Zubair Afzal ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Response Rate ◽  
Checkpoint Inhibitors ◽  
Progression Free Survival ◽  
Normal Weight ◽  
Obese Patients ◽  
Small Cell Lung ◽  
Free Survival ◽  
Radiographic Response ◽  
Nsclc Patients

e21209 Background: Immune checkpoint inhibitors (ICI) are now the standard of care in the treatment of non-small cell lung cancer (NSCLC). ICIs may be used as monotherapy or in combination with chemotherapy. Increased recruitment of inflammatory cells in the tumor micro-environment is associated with a poor response to ICIs. Although obesity is a risk factor for many types of cancers, including lung cancer, it is associated with a low systemic inflammation state. This creates an effect known as the “obesity paradox,” resulting in better treatment-related outcomes in overweight and obese patients receiving ICIs. However, in obese patients, the neutralizing interleukin (IL) - 1β level is high, which can decrease the responsiveness to ICI. We aim to study the effect of increased weight on treatment-related outcomes in NSCLC patients receiving ICI. Methods: We conducted a retrospective analysis on 178 NSCLC patients treated with ICIs, such as pembrolizumab, nivolumab, ipilimumab/nivolumab or atezolizumab, alone or in combination with chemotherapy. Overweight was defined as having a BMI of 25 – 29.9 while obesity was defined as having a BMI of ≥ 30. Overall survival (OS), progression free survival (PFS), best radiographic response, and the time to achieve radiographic response were evaluated. Cox regression univariate and multivariate analyses were performed. Logistic regression and Chi-square tests were applied. Results: Of the 178 patients with NSCLC, 81% had adenocarcinoma, and 19% had squamous, adenosquamous, or large cell carcinoma. The majority of patients were female (56.2% vs. 43.8%). Overall, 48.6% patients were overweight or obese. The objective response rate (ORR) was 45.1% and the disease control rate (DCR) was 75.8%. The ORR was 37% in overweight/obese patients compared to 52% in patients with a normal weight (p = 0.06). The DCR was 76% vs. 73.9%, (p = 0.7). The median time to achieve the best radiographic response was 3.7 months in overweight/obese patients compared to 2.5 months in those of normal weight (p = 0.2). A considerably higher proportion of the patients progressed in overweight/obese category (80.7% vs. 69.3%, P = 0.08). However, there was no significant difference in median PFS between the two categories (7.4 vs. 8.1 months, P = 0.2). The overall survival was not significant different between both categories (15.9 vs. 16.8 months, P = 0.5). Conclusions: Our study suggests that obesity and overweight status can result in a low response rate to ICIs in NSCLC patients and can delay the time to achieve the best radiographic response per RECIST criteria. However, we did not observe any significant impact on the overall or progression-free survival. A large, population-based study will help to elucidate the impact of weight on the responsiveness to ICI.

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