First-Line Gefitinib in Patients With Advanced Non–Small-Cell Lung Cancer Harboring SomaticEGFRMutations

2008 ◽  
Vol 26 (15) ◽  
pp. 2442-2449 ◽  
Author(s):  
Lecia V. Sequist ◽  
Renato G. Martins ◽  
David Spigel ◽  
Steven M. Grunberg ◽  
Alexander Spira ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Egfr Mutation ◽  
Advanced Nsclc ◽  
Response Rate ◽  
Small Cell ◽  
Egfr Mutations ◽  
Small Cell Lung ◽  
First Line ◽  
Tki Resistance ◽  
Grade 3

PurposeSomatic mutations in the epidermal growth factor receptor (EGFR) correlate with increased response in patients with non–small-cell lung cancer (NSCLC) treated with EGFR tyrosine kinase inhibitors (TKIs). The multicenter iTARGET trial prospectively examined first-line gefitinib in advanced NSCLC patients harboring EGFR mutations and explored the significance of EGFR mutation subtypes and TKI resistance mechanisms.Patients and MethodsChemotherapy-naïve patients with advanced NSCLC with ≥ 1 clinical characteristic associated with EGFR mutations underwent direct DNA sequencing of tumor tissue EGFR exons 18 to 21. Patients found to harbor any EGFR mutation were treated with gefitinib 250 mg/d until progression or unacceptable toxicity. The primary outcome was response rate.ResultsNinety-eight patients underwent EGFR screening and mutations were detected in 34 (35%). EGFR mutations were primarily exon 19 deletions (53%) and L858R (26%) though 21% of mutation-positive cases had less common subtypes including exon 20 insertions, T790M/L858R, G719A, and L861Q. Thirty-one patients received gefitinib. The response rate was 55% (95% CI, 33 to 70) and median progression-free survival was 9.2 months (95% CI, 6.2 to 11.8). Therapy was well tolerated; 13% of patients had grade 3 toxicities including one grade 3 pneumonitis. Two patients with classic activating mutations exhibited de novo gefitinib resistance and had concurrent genetic anomalies usually associated with acquired TKI resistance, specifically the T790M EGFR mutation and MET amplification.ConclusionFirst-line therapy with gefitinib administered in a genotype-directed fashion to patients with advanced NSCLC harboring EGFR mutations results in very favorable clinical outcomes with good tolerance. This strategy should be compared with combination chemotherapy, the current standard of care.

scholarly journals Treatment and Outcomes of Metastatic Non-Small-Cell Lung Cancer Harboring Uncommon EGFR Mutations: Are They Different from Those with Common EGFR Mutations?

Biology ◽  
2020 ◽  
Vol 9 (10) ◽  
pp. 326
Author(s):  
Hyun Ae Jung ◽  
Sehhoon Park ◽  
Jong-Mu Sun ◽  
Se-Hoon Lee ◽  
Jin Seok Ahn ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Egfr Mutation ◽  
Response Rate ◽  
Small Cell ◽  
Egfr Mutations ◽  
Small Cell Lung ◽  
First Line ◽  
Compound Mutation ◽  
Egfr Tki ◽  
Egfr Tkis

Approximately 10% of the epidermal growth factor receptor (EGFR) mutations in non-small-cell lung cancer (NSCLC) are uncommon EGFR mutations. Although the efficacy of second (2G) or third generation (3G) EGFR tyrosine kinase inhibitors (EGFR-TKIs) in the patients with uncommon EGFR mutation has been proven, further studies are warranted to define the optimal treatment approach for uncommon EGFR mutation-positive NSCLC. This study retrospectively investigated the treatment patterns and outcomes of patients with uncommon EGFR mutation-positive NSCLC from January 2011 to December 2019 at the Samsung Medical Center, Seoul, Korea. During the study, 2121 patients with EGFR mutation-positive NSCLC received first-generation (1G, gefitinib or erlotinib) or 2G EGFR-TKI (afatinib) as the first-line (1L) systemic therapy. Of this, 135 (6.4%) patients harbored uncommon EGFR mutations. Of 135, 54 (40%, 54/135) patients had overlapping mutations with major EGFR mutations. The objective response rate (ORR) for the 1L EGFR-TKI was 63.3%. The median progression-free survivals (PFSs) were 8.6 months (95% CI: 3.8–13.5), 11.7 months (95% CI: 6.6–16.7), 7.7 months (95% CI: 4.9–17.4), and 5.0 months (95% CI: 3.7–6.1) for major uncommon EGFR mutation (G719X, L861Q), compound mutation with major EGFR mutation (Del 19 or EGFR exon 21 p.L858R), other compound mutation, and other uncommon mutations, respectively. The median overall survivals (OSs) were 25.6 months (16.9–34.2), 28.8 (95% CI: 24.4–33.4), 13.5 months (95% CI: 7.4–27.8), and 9.4 months (95% CI: 3.4–10.5) for major uncommon EGFR mutation (G719X), compound mutation with major EGFR mutation (Del 19 or EGFR exon 21 p.L858R), other compound mutation, and other uncommon mutations, respectively. The response rate, median PFS, and OS were 63.3%, 16.3 months (95% CI: 15.6–16.9), and 37.5 months (95% CI: 35.4–39.6) for common EGFR mutation-positive NSCLC. After failing 1L EGFR-TKI, repeated tissue or liquid biopsy were carried out on 44.9% (35/78) of patients with T790M detected in 10/35 (28.6%) patients. With subsequent 3G EGFR-TKI after failing the first-line EGFR-TKI, the ORR and PFS for 3G EGFR-TKI were 80% and 8.9 months (95% CI: 8.0–9.8). These patients showed a median OS of 34.6 months (95% CI: 29.8–39.4). The ORR, PFS and OS were poorer in patients with uncommon (especially other compound and other uncommon mutation) than those with common EGFR mutations. T790M was detected in 28.6% of the uncommon EGFR mutation-positive patients for whom prior 1G/2G EGFR-TKIs failed and underwent repeat biopsy at the time of progression.

Phase II study of docetaxel and cisplatin in advanced non-small-cell lung cancer.

1998 ◽  
Vol 16 (5) ◽  
pp. 1948-1953 ◽  
Author(s):  
J Zalcberg ◽  
M Millward ◽  
J Bishop ◽  
M McKeage ◽  
A Zimet ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Phase Ii ◽  
Advanced Nsclc ◽  
Response Rate ◽  
Phase Ii Study ◽  
Performance Status ◽  
Objective Response ◽  
Small Cell ◽  
Small Cell Lung ◽  
Grade 3

PURPOSE Docetaxel (Taxotere, Rhone-Poulenc Rorer, Antony, France) and cisplatin are two of the most active single agents used in the treatment of non-small-cell lung cancer (NSCLC). A recently reported phase I study of the combination of docetaxel and cisplatin recommended a dose of 75 mg/m2 of both drugs every 3 weeks for subsequent phase II study. PATIENTS AND METHODS Eligible patients were aged 18 to 75 years with a World Health Organization (WHO) performance status < or = 2 and life expectancy > or = 12 weeks, with metastatic and/or locally advanced NSCLC proven histologically or cytologically. Patients were not permitted to have received prior chemotherapy, extensive radiotherapy, or any radiotherapy to the target lesion and must have had measurable disease. Concurrent treatment with colony-stimulating factors (CSFs) or prophylactic antibiotics was not permitted. Docetaxel (75 mg/m2) in 250 mL 5% dextrose was given intravenously (i.v.) over 1 hour immediately before cisplatin (75 mg/m2) in 500 mL normal saline given i.v. over 1 hour in 3-week cycles. Premedication included ondansetron, dexamethasone, promethazine, and standard hyperhydration with magnesium supplementation. RESULTS A total of 47 patients, two thirds of whom had metastatic disease, were entered onto this phase II study. The majority of patients were male (72%) and of good (WHO 0 to 1) performance status (85%). All 47 patients were assessable for toxicity and 36 were for response. Three patients were ineligible and eight (17%) discontinued treatment because of significant toxicity. In assessable patients, the overall objective response rate was 38.9% (95% confidence limits [CL], 23.1% to 56.5%), 36.1% had stable disease, and 25% progressive disease. On an intention-to-treat analysis, the objective response rate was 29.8%. Median survival was 9.6 months and estimated 1-year survival was 33%. Significant (grade 3/4) toxicities included nausea (26%), hypotension (15%), diarrhea (13%), and dyspnea mainly related to chest infection (13%). One patient experienced National Cancer Institute (NCI) grade 3 neurosensory toxicity after eight cycles. Grade 3/4 neutropenia was common and occurred in 87% of patients, but thrombocytopenia > or = grade 3 was rare (one patient). Significant (grade 3/4) abnormalities of magnesium levels were common (24%). Febrile neutropenia occurred in 13% of patients and neutropenic infection in 11%, contributing to two treatment-related deaths. No neutropenic enterocolitis or severe fluid retention was reported. CONCLUSION Compared with other active regimens used in this setting, the combination of docetaxel and cisplatin in advanced NSCLC is an active regimen with a similar toxicity profile to other combination regimens.

Randomized Phase III Study of Gemcitabine-Cisplatin Versus Etoposide-Cisplatin in the Treatment of Locally Advanced or Metastatic Non–Small-Cell Lung Cancer

1999 ◽  
Vol 17 (1) ◽  
pp. 12-12 ◽  
Author(s):  
Felipe Cardenal ◽  
M. Paz López-Cabrerizo ◽  
Antonio Antón ◽  
Vicente Alberola ◽  
Bartomeu Massuti ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Disease Progression ◽  
Cell Lung Cancer ◽  
Advanced Nsclc ◽  
Response Rate ◽  
Small Cell ◽  
Phase Iii ◽  
Small Cell Lung ◽  
Grade 3

PURPOSE: We conducted a randomized trial to compare gemcitabine-cisplatin with etoposide-cisplatin in the treatment of patients with advanced non–small-cell lung cancer (NSCLC). The primary end point of the comparison was response rate. PATIENTS AND METHODS: A total of 135 chemotherapy-naive patients with advanced NSCLC were randomized to receive either gemcitabine 1,250 mg/m2 intravenously (IV) days 1 and 8 or etoposide 100 mg/m2 IV days 1 to 3 along with cisplatin 100 mg/m2 IV day 1. Both treatments were administered in 21-day cycles. One hundred thirty-three patients were included in the intent-to-treat analysis of response. RESULTS: The response rate (externally validated) for patients given gemcitabine-cisplatin was superior to that for patients given etoposide-cisplatin (40.6% v 21.9%; P = .02). This superior response rate was associated with a significant delay in time to disease progression (6.9 months v 4.3 months; P = .01) without an impairment in quality of life (QOL). There was no statistically significant difference in survival time between both arms (8.7 months for gemcitabine-cisplatin v 7.2 months for etoposide-cisplatin; P = .18). The overall toxicity profile for both combinations of drugs was similar. Nausea and vomiting were reported more frequently in the gemcitabine arm than in the etoposide arm. However, the difference was not significant. Gemcitabine-cisplatin produced less grade 3 alopecia (13% v 51%) and less grade 4 neutropenia (28% v 56% ) but more grade 3 and 4 thrombocytopenia (56% v 13%) than did etoposide-cisplatin. However, there were no thrombocytopenia-related complications in the gemcitabine arm. CONCLUSION: Compared with etoposide-cisplatin, gemcitabine-cisplatin provides a significantly higher response rate and a delay in disease progression without impairing QOL in patients with advanced NSCLC.

Prospective phase II trial of a combination of gemcitabine, cisplatin and UFT as first-line treatment in patients with advanced, unresectable, non-small cell lung carcinoma

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 18109-18109
Author(s):  
S. S. Jin ◽  
Y. Min ◽  
H. Kim ◽  
J. Ahn ◽  
Y. Jegal ◽  
...  
Keyword(s):  
Survival Time ◽  
Overall Response Rate ◽  
Advanced Nsclc ◽  
Response Rate ◽  
Performance Status ◽  
Small Cell ◽  
Time To Progression ◽  
Small Cell Lung ◽  
First Line ◽  
Grade 3

18109 Background: Most patients with advanced non-small cell lung cancer (NSCLC) receive either single agents or doublet chemotherapy. For non-elderly patients in good performance status, platinum-based double combinations represent the standard treatment. And oral UFT had the survival advantage in adjuvant setting. Therefore we performed a phase II study using the combination of gemcitabine, cisplatin and UFT as a first line therapy in patients with advanced NSCLC. Methods: Eligible patients had histologically or cytologically confirmed stage IIIB or IV NSCLC with good performance status and were chemotherapy-naive. This study was two-stage design and planned number of patients was forty-seven. Gemcitabine (1,250 mg/m2, 10 mg/kg/min on days 1 and 8) and cisplatin (75 mg/m2 on day 1) were injected intravenously and UFT (400 mg/day) was administered orally on day 1–14. Treatment repeated every 3 weeks. Primary end point was overall response rate and secondary end points were overall survival, time to progression and toxicity. Results: Thirty seven patients with advanced NSCLC were enrolled. The median age of the patients was 60 years (range: 44 to 72). The performance status (WHO) was 0 in 4, 1 in 30 and 2 in 3 patients. Twenty three patients completed six cycles. Complete response was achieved in 1 (3%) patient, partial response in 22 (59%) patients, stable disease in 9 (24%) patients. Overall response rate was 62% on intent to treat basis. Among patients who response evaluation was possible (33 patients), response rate was 70%. The median survival time was 14.5 months (95% CI 6.9, 22.3) and the 1 year survival was 35% and then median time to progression was 3.4 months(95% CI 3, 3.9). Toxicities were moderate and mostly hematological adverse events. Grade 3/4 neutropenia occurred in 37%, 5 patients with febrile neutropenia. Grade 3/4 anemia and thrombocypenia was occurred in 37% and 5%. Nonhematologic toxicities were mild. Conclusion: The combination therapy consisted of gemcitabine, cisplatin and UFT is active and well tolerable first line regimen for NSCLC patients. No significant financial relationships to disclose.

Angiogenesis inhibitor plus erlotinib versus erlotinib alone as first-line for advanced non-small cell lung-cancer harboring EGFR mutation.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 9569-9569 ◽  
Author(s):  
Thierry Landre ◽  
Gaetan Des Guetz ◽  
Kader Chouahnia ◽  
Boris Duchemann ◽  
Jean F. Morere ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Egfr Mutation ◽  
Advanced Nsclc ◽  
Small Cell ◽  
Line Treatment ◽  
Small Cell Lung ◽  
First Line ◽  
Anti Vegf ◽  
First Line Treatment

9569 Background: Erlotinib is indicated in first line treatment for patients with Non-Small-Cell-Lung cancer (NSCLC) harbouring EGFR mutation. Addition of anti-VEGF in combination with erlotinib in this setting is controversial. Methods: We performed a meta-analysis of randomized trials comparing VEGF inhibitor plus erlotinib with erlotinib alone in first line treatment for advanced NSCLC harbouring EGFR mutation. The outcomes included overall survival (OS), progression-free survival (PFS) objective response rate (ORR), and median duration of response (DOR). A fixed-effect model was used. Results: Four studies evaluated bevacizumab + erlotinib (ARTEMIS, NEJ026, J025667, Stinchcombe et al), and one study evaluated ramucirumab + erlotinib (RELAY). These five eligible studies included 1230 non-squamous NSCLC patients (654 with Ex19del and 568 with Leu858Arg);. Most of the patients were women (63%), Asian (85%) and non-smokers (60%), with a median age of 64 years. The combination (anti-VEGF + erlotinib) was significantly associated with improvement of PFS (hazards ratio [HR]: 0.59, 95%CI: 0.51-0.69, p < 0.00001). Improvement in PFS was seen across all subgroups analyzed. Interim analysis of OS (HR: 0.90, 95%CI; 0.68-1.19, p = 0.45) and ORR (odds ratio [OR], 1.19, 0.91-1.55, p = 0.21) were not statistically significant. DOR was statistically longer with combination (p < 0.005). Conclusions: For patients with untreated advanced NSCLC with EGFR mutation, the anti-VEGF combination with erlotinib, compared with erlotinib alone, is associated with significantly improved PFS and DOR, but mature data for OS are needed to confirm the benefit of this strategy.

scholarly journals Comparative Safety of Immune Checkpoint Inhibitors and Chemotherapy in Advanced Non-Small Cell Lung Cancer: A Systematic Review and Network Meta-Analysis

2021 ◽  
Author(s):  
Ching-Yi Chen ◽  
Chi-Hsien Huang ◽  
Wang-Chun Chen ◽  
Ming-Shyan Huang ◽  
Yu-Feng Wei
Keyword(s):  
Lung Cancer ◽  
Immune Checkpoint Inhibitors ◽  
Advanced Nsclc ◽  
Checkpoint Inhibitors ◽  
Small Cell ◽  
Small Cell Lung ◽  
First Line ◽  
Grade 3 ◽  
Nsclc Patients ◽  
Combination Regimens

Abstract Backgrounds: Immune checkpoint inhibitors (ICIs) alone or in combination with chemotherapy (CT) are the standard of care for first-line therapy in metastatic non-small cell lung cancer (NSCLC) patients without actionable mutations. The safety ranking of different ICI and CT combination regimens has not been investigated. This study was aimed to provide a toxicity profile and safety ranking of different ICI and CT combination regimens.Methods: We performed comprehensive searches of phase 2 and 3 randomized clinical trials (RCTs) comparing different ICI regimens (alone or combination) or CT for the first-line treatment of advanced NSCLC. Outcomes of interest were the cumulative incidence of any treatment-related adverse events (TRAEs), grade 3-5 TRAEs (grade 3-5), any immune-related adverse events (irAEs), and grade 3-5 irAEs (grade 3-5). Odds ratios and 95% credible intervals were calculated as summary statistics to quantify the effect of different ICI combination regimens. Results: We included 23 RCTs from 2016 to 2021 with a total of 14,378 patients. The incidence of any TRAEs and grade 3-5 TRAEs ranked from high to low were ICI-CT (probability: 74.88%), ICI-ICI-CT (50.60%), CT alone (74.79%), ICI-ICI (98.37%), and ICI monotherapy (99.37%). Adding CT to ICI regimens resulted in a higher incidence of any grade or grade 3-5 TRAEs compared to ICI-ICI combinations or ICI monotherapy. However, ICI-ICI-CT combinations did not result in a higher incidence of TRAEs than ICI-CT combinations. For any irAEs and grade 3-5 irAEs, the ranking was ICI-ICI (probability: 97.38), ICI monotherapy (96.98%), ICI-CT (99.44%), and CT alone (99.98%). Notably, the incidence of any grade and grade 3-5 irAEs was lower when adding CT to ICI monotherapy. Conclusion: Lack of head-to-head comparisons, these findings provide evidence for clinical decision-making when considering different ICI combination regimens for advanced NSCLC patients.

Phase II study of irinotecan plus S-1 combination for previously untreated advanced non-small cell lung cancer: Hokkaido Lung Cancer Clinical Study Group 0601

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e19012-e19012
Author(s):  
S. Oizumi ◽  
K. Akie ◽  
S. Ogura ◽  
N. Shinagawa ◽  
S. Fukumoto ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Phase Ii ◽  
Cell Lung Cancer ◽  
Advanced Nsclc ◽  
Response Rate ◽  
Small Cell ◽  
Severe Toxicity ◽  
Small Cell Lung ◽  
Grade 3

e19012 Background: Platinum-containing therapy is a standard first-line treatment for advanced non-small cell lung cancer (NSCLC). Platinum-free regimens can be alternative if they can provide similar efficacy with better tolerability. This study evaluated the efficacy and safety for combination of irinotecan and S-1, a newly developed oral 5-fluorouracil derivative, for chemotherapy-naïve advanced NSCLC. Methods: In this multicenter phase II trial, we initially planned to enroll 40 patients. Chemotherapy consisted of 4-week cycles of irinotecan (100 mg/m2 IV, day 1 and 15) and S-1 (80 mg/m2 orally, day 1–14). Primary end point was response rate; secondary endpoints were overall survival (OS), progression-free survival (PFS), and safety. Association of UGT1A1 genotypes (*6 and *28) with frequency of severe toxicity was also examined. Results: A total of 112 cycles was administered into 40 patients (median, 3 cycles: range, 1–6). Median age was 64 years (range, 42–75); 29 patients (73%) had adenocarcinoma, and 8 patients (20%) had squamous cell carcinoma. Majority of the patients (32 cases, 80%) had stage IV disease. Twelve patients exhibited partial response (PR), and 17 patients exhibited stable disease (SD), resulting in response rate of 30% [95% confidence interval (95% CI), 16.6–46.5] and disease control rate of 72.5% (95% CI, 56.1–85.4). Median OS and PFS were 13.8 months (95% CI, 10.7–16.9) and 4.7 months (95% CI, 3.4–6.0), respectively. Hematological toxicities of grade 3 or 4 were neutropenia (32.5%) and anemia (5.0%). The most common non-hematologic toxicities of grade 3 or 4 included diarrhea (15.0%) and anorexia (17.5%). There were no treatment-related deaths. Among the 40 patients, there were 1 homozygous and 8 heterozygous for UGT1A1*6, whereas 7 heterozygous for UGT1A1*28; none of the patients had both genotypes. Patients with homozygous or heterozygous for UGT1A1*6 showed a trend for high incidence of grade 3 diarrhea (p = 0.055). No association of UGT1A1*28 with severe toxicity was observed in this study. Conclusions: Irinotecan and S-1 combination is an alternative treatment with tolerable toxicity for previously untreated advanced NSCLC. No significant financial relationships to disclose.

scholarly journals Effectiveness and Safety of EGFR-TKI Rechallenge Treatment in Elderly Patients with Advanced Non-Small-Cell Lung Cancer Harboring Drug-Sensitive EGFR Mutations

Medicina ◽  
2021 ◽  
Vol 57 (9) ◽  
pp. 929
Author(s):  
Yutaka Yamada ◽  
Hisao Imai ◽  
Tomohide Sugiyama ◽  
Hiroyuki Minemura ◽  
Kenya Kanazawa ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Adverse Events ◽  
Elderly Patients ◽  
Advanced Nsclc ◽  
Small Cell ◽  
Egfr Mutations ◽  
Small Cell Lung ◽  
First Line ◽  
Tki Treatment ◽  
Egfr Tki

Background and Objectives: Epidermal growth factor receptor–tyrosine kinase inhibitors (EGFR-TKIs) are effective first-line chemotherapeutic agents for patients with advanced non-small-cell lung cancer (NSCLC) harboring drug-sensitive EGFR mutations. However, the effectiveness of EGFR-TKI rechallenge after first-line EGFR-TKI treatment is not sufficient in elderly patients (over 75 years of age) harboring drug-sensitive EGFR mutations. Therefore, we investigated the effectiveness and safety of EGFR-TKI rechallenge after first-line EGFR-TKI treatment in elderly patients with advanced NSCLC harboring drug-sensitive EGFR mutations. Materials and Methods: Between April 2008 and December 2015, we analyzed 78 elderly patients with advanced NSCLC harboring drug-sensitive EGFR mutations with first-line EGFR-TKI treatment at four Japanese institutions. We retrospectively evaluated the clinical effectiveness and safety profiles of EGFR-TKI rechallenge after first-line EGFR-TKI treatment in elderly patients with advanced NSCLC harboring drug-sensitive EGFR mutations (exon 19 deletion/exon 21 L858R mutation). Results: Twenty-two patients in the cohort were rechallenged with EGFR-TKI. The median age was 79.5 years (range 75–87 years). Despite the fact that it was a retrospective analysis, even with EGFR-TKI rechallenge treatment the response rate was 23%, progression-free survival was 5.3 months, and overall survival was 14.4 months. Common adverse events included rash acneiform, paronychia, diarrhea, and anorexia. There were no treatment-related deaths. Due to the occurrence of adverse events of grade 2 or more, dose reduction was performed in 15 (68.2%) of 22 cases. Conclusions: EGFR-TKI rechallenge treatment after first-line EGFR-TKI treatment in elderly patients with advanced NSCLC harboring drug-sensitive EGFR mutations was one of the limited, safe and effective treatment options for elderly EGFR-positive lung cancer patients.

scholarly journals Are anti-PD1 and anti-PD-L1 alike? The non-small-cell lung cancer paradigm

2020 ◽  
Vol 14 (2) ◽  
Author(s):  
Giuseppe Luigi Banna ◽  
Ornella Cantale ◽  
Melissa Bersanelli ◽  
Marzia Del Re ◽  
Alex Friedlaender ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Advanced Nsclc ◽  
Response Rate ◽  
Indirect Evidence ◽  
Small Cell ◽  
Small Cell Lung ◽  
First Line ◽  
Nsclc Patients

Anti-PD1 and anti-PD-L1 agents may have intrinsic and clinically relevant differences in the treatment of non-small cell lung cancer (NSCLC) patients. By reviewing currently available indirect evidence on these agents for NSCLC treatment, highlighting possible inter- and intra-class dissimilarities, anti-PD1 agents showed a higher response rate and a better outcome when combined with chemotherapy for the first-line treatment of patients with squamous and PD-L1 low advanced NSCLC, as compared to anti-PD-L1 agents. Conversely, anti-PD-L1 agents were responsible for less severe adverse events (AEs), particularly, immunerelated AEs. These differences could be explained by their different specific properties. Considering possible differences between anti-PD1 and anti-PD-L1 agents could be clinically relevant for treatment tailoring and inspiring new investigational approaches.

Efficacy and safety of PD-1/PD-L1 antibody combined with chemotherapy as second-line or third-line treatment for metastatic small cell lung cancer.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e20574-e20574
Author(s):  
Jun Wang ◽  
Beibei Yin ◽  
Yaping Guan ◽  
Dongfeng Feng
Keyword(s):  
Lung Cancer ◽  
Response Rate ◽  
Objective Response ◽  
Small Cell ◽  
Efficacy And Safety ◽  
Small Cell Lung ◽  
First Line ◽  
Platinum Based Chemotherapy ◽  
Extensive Stage ◽  
Grade 3

e20574 Background: For a small subset of patients, immune checkpoint blockade heralds a promising strategy for achieving disease control in small cell lung cancer (SCLC). Nivolumab or pembrolizumab monotherapy has been granted accelerated approval for treatment of patients with extensive-stage SCLC with disease progression after platinum-based chemotherapy and at least one other line of therapy. Moreover, Based on IMpower133 and CASPIAN data, addition of PD-L1 antibody such as atezolizumab or durvalumab to first-line platinum-based chemotherapy prolongs overall survival over chemotherapy alone. However, it remains exclusive that whether PD-1/PD-L1 antibody combined with chemotherapy is effective against extensive-stage SCLC when progressed on previous chemotherapy. Methods: We reviewed patients with extensive-stage SCLC who have failed in first-line or beyond chemotherapy and received PD-1/PD-L1 antibodies with chemotherapy in a single institute. The efficacy and safety were evaluated. The primary end point was the objective response rate according to Response Evaluation Criteria in Solid Tumors, version 1.1. Results: A total of 11 patients were included in this retrospective cohort study. The median age was 46 years (range from 29 to 62). Seven patients were male. Four were current or former smokers. Six received two prior therapies. Nine had previously received radiation therapy. PD-1 and PD-L1 inhibitors were administrated in 5 and 6 patients, respectively. No patient had a complete response. 2 patients had a partial response, and the objective response rate was 18.2%. 5 patients were evaluated as stable disease with a disease control rate of 63.6%. The median overall survival and progression-free survival was 3.0 months and 2.3 months, respectively. A patient with partial response had a long duration of response of 5.2 months. The most common grade 3 or 4 treatment-related were neutropenia, anemia, and decreased neutrophil count. Most immune-related adverse events were grade 1 or 2, with rash, pruritus and hypothyroidism being the most common, and 1 patient had grade 3 pneumonia. Conclusions: Immunotherapy plus chemotherapy could be beneficial for a subgroup of extensive-stage SCLC patients who have progressed after previous chemotherapy. Further prospective, randomized studies are warranted.

Sign in / Sign up

Export Citation Format

Share Document