Extensive-Stage Small-Cell Lung Cancer: First-Line and Second-Line Treatment Options

2022 ◽  
Author(s):  
Jon Zugazagoitia ◽  
Luis Paz-Ares
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Recent Progress ◽  
Treatment Options ◽  
Therapeutic Strategies ◽  
Small Cell ◽  
Small Cell Lung ◽  
First Line ◽  
Extensive Stage

Extensive-stage small-cell lung cancer is a therapeutically challenging disease. After more than two decades without clinical progress, the addition of programmed cell death protein 1 axis blockade to platinum-based chemotherapy has demonstrated sustained overall survival benefit and represents the current standard of care in the first-line setting. Despite this benefit, resistance emerges relatively rapidly in virtually all patients. Although newer treatments are being incorporated in the relapse setting, marked therapeutic resistance is typically observed in patients with relapsed small-cell lung cancer (SCLC), underscoring the need of developing more effective therapies in this setting. Notably, recent progress in the understanding of the molecular biology of SCLC might bring possibilities toward molecularly informed therapeutic strategies for patients with SCLC, which could have a significant impact for improving outcomes in this disease. Here, we review current treatment options and recent progress made in the first-line and relapsed SCLC, including the role of biomarkers and new evolving therapeutic strategies.

scholarly journals Front Line Applications and Future Directions of Immunotherapy in Small-Cell Lung Cancer

Cancers ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 506
Author(s):  
Selina K. Wong ◽  
Wade T. Iams
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Checkpoint Inhibitors ◽  
Standard Of Care ◽  
Small Cell ◽  
Small Cell Lung ◽  
First Line ◽  
Limited Stage ◽  
Extensive Stage

After being stagnant for decades, there has finally been a paradigm shift in the treatment of small-cell lung cancer (SCLC) with the emergence and application of immune checkpoint inhibitors (ICIs). Multiple trials of first-line ICI-chemotherapy combinations have demonstrated survival benefit compared to chemotherapy alone in patients with extensive-stage SCLC, establishing this as the new standard of care. ICIs are now being applied in the potentially curative limited-stage setting, actively being investigated as concurrent treatment with chemoradiation and as adjuvant treatment following completion of chemoradiation. This review highlights the evidence behind the practice-changing addition of ICIs in the first-line setting of extensive-stage SCLC, the potentially practice-changing immunotherapy trials that are currently underway in the limited-stage setting, and alternate immunotherapeutic strategies being studied in the treatment of SCLC.

scholarly journals Partial Response in an RRx-001-Primed Patient with Refractory Small-Cell Lung Cancer after a Third Introduction of Platinum Doublets

2016 ◽  
Vol 9 (2) ◽  
pp. 285-289 ◽  
Author(s):  
Corey A. Carter ◽  
Bryan Oronsky ◽  
Scott Caroen ◽  
Jan Scicinski ◽  
Aiste Degesys ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Partial Response ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Small Cell Lung ◽  
First Line ◽  
Platinum Drug ◽  
First Line Therapy ◽  
Extensive Stage

Small-cell lung cancer (SCLC), initially exquisitely sensitive to first-line cisplatin/etoposide, invariably relapses and acquires a multidrug chemoresistant phenotype that generally renders retreatment with first-line therapy both futile and counterproductive. This report presents the case of a 77-year-old Caucasian male with extensive-stage refractory SCLC who was restarted on platinum doublets as part of a clinical trial called TRIPLE THREAT (NCT02489903) involving pretreatment with the epi-immunotherapeutic agent RRx-001, and who achieved a partial response after only 4 cycles. The patient had received a platinum drug twice before, in 2009 for a diagnosis of non-small-cell lung cancer (squamous cell carcinoma) and in 2015 for SCLC, suggesting that RRx-001 pretreatment may sensitize or resensitize refractory SCLC patients to first-line chemotherapy.

scholarly journals Comparative efficacy and safety of first-line treatments for advanced non-small cell lung cancer with ALK-rearranged: a meta-analysis of clinical trials

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Hao-chuan Ma ◽  
Yi-hong Liu ◽  
Kai-lin Ding ◽  
Yu-feng Liu ◽  
Wen-jie Zhao ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Adverse Events ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Treatment Options ◽  
Small Cell ◽  
Efficacy And Safety ◽  
Small Cell Lung ◽  
First Line ◽  
Grade 3

Abstract Background Whereas there are many pharmacological interventions prescribed for patients with advanced anaplastic lymphoma kinase (ALK)- rearranged non-small cell lung cancer (NSCLC), comparative data between novel generation ALK-tyrosine kinase inhibitors (TKIs) remain scant. Here, we indirectly compared the efficacy and safety of first-line systemic therapeutic options used for the treatment of ALK-rearranged NSCLC. Methods We included all phase 2 and 3 randomised controlled trials (RCTs) comparing any two or three treatment options. Eligible studies reported at least one of the following outcomes: progression free survival (PFS), overall survival (OS), objective response rate (ORR), or adverse events of grade 3 or higher (Grade ≥ 3 AEs). Subgroup analysis was conducted according to central nervous system (CNS) metastases. Results A total of 9 RCTs consisting of 2484 patients with 8 treatment options were included in the systematic review. Our analysis showed that alectinib (300 mg and 600 mg), brigatinib, lorlatinib and ensartinib yielded the most favorable PFS. Whereas there was no significant OS or ORR difference among the ALK-TKIs. According to Bayesian ranking profiles, lorlatinib, alectinib 600 mg and alectinib 300 mg had the best PFS (63.7%), OS (35.9%) and ORR (37%), respectively. On the other hand, ceritinib showed the highest rate of severe adverse events (60%). Conclusion Our analysis indicated that alectinib and lorlatinib might be associated with the best therapeutic efficacy in first-line treatment for major population of advanced NSCLC patients with ALK-rearrangement. However, since there is little comparative evidence on the treatment options, there is need for relative trials to fully determine the best treatment options as well as the rapidly evolving treatment landscape.

Use of Immunotherapy in Extensive-Stage Small Cell Lung Cancer

Oncology ◽  
2020 ◽  
Vol 98 (11) ◽  
pp. 749-754 ◽  
Author(s):  
Venu Madhav Konala ◽  
Bhaskar Reddy Madhira ◽  
Sara Ashraf ◽  
Stephen Graziano
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Initial Response ◽  
The United States ◽  
Small Cell ◽  
Small Cell Lung ◽  
First Line ◽  
Stage Disease ◽  
Extensive Stage

Lung cancer is a leading cause of cancer death in the United States and around the world. Approximately 13% of lung cancers are small cell lung cancer (SCLC). SCLC is generally classified as a limited-stage and extensive-stage disease depending on the extent of involvement. For patients with the extensive-stage disease, until recently, chemotherapy alone has been the recommended treatment, although radiotherapy could be used in select patients for palliation of symptoms. The standard of care for extensive-stage SCLC is platinum doublet chemotherapy with either cisplatin or carboplatin in combination with etoposide. Even though first-line therapy has an initial response rate of 60–80%, the prognosis is poor, with overall survival of 10–12 months. The only FDA-approved second line of therapy is topotecan, approved both as an intravenous formulation as well as an oral formulation, with response rates of 6–12% in chemorefractory disease and 15–37% in chemosensitive disease. Immunotherapy has recently been approved as a first-line agent in metastatic SCLC in combination with chemotherapy. It is also approved as a third-line agent in metastatic SCLC after the failure of two chemotherapy regimens. The FDA approved four drugs, two of them being PD-1 inhibitors (pembrolizumab, nivolumab), and two of them being PD-L1 inhibitors (atezolizumab and durvalumab) in SCLC. This review article summarizes the significance of immunotherapy in the treatment of extensive-stage SCLC, its side effects, and limitations.

scholarly journals Initial management of small-cell lung cancer (limited- and extensive-stage) and the role of thoracic radiotherapy and first-line chemotherapy: a systematic review

2019 ◽  
Vol 26 (3) ◽  
Author(s):  
A. Sun ◽  
L. D. Durocher-Allen ◽  
P. M. Ellis ◽  
Y. C. Ung ◽  
J. R. Goffin ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Systematic Review ◽  
Overall Survival ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Small Cell Lung ◽  
First Line ◽  
Platinum Agent ◽  
Extensive Stage

Background Patients with limited-stage (ls) or extensive-stage (es) small-cell lung cancer (sclc) are commonly given platinum-based chemotherapy as first-line treatment. Standard chemotherapy for patients with ls sclc includes a platinum agent such as cisplatin combined with the non-platinum agent etoposide. The objective of the present systematic review was to investigate the efficacy of adding radiotherapy to chemotherapy in patients with es sclc and to determine the appropriate timing, dose, and schedule of chemotherapy or radiation for patients with sclc.Methods The medline and embase databases were searched for randomized controlled trials (rcts) comparing treatment with radiotherapy plus chemotherapy against treatment with chemotherapy alone in patients with es sclc. Identified rcts were also included if they compared various timings, doses, and schedules of treatment for patients with es sclc or ls sclc.Results Sixty-four rcts were included. In patients with ls sclc, overall survival was greatest with platinum– etoposide compared with other chemotherapy regimens. In patients with es sclc, overall survival was greatest with chemotherapy containing platinum–irinotecan than with chemotherapy containing platinum–etoposide (hazard ratio: 0.84; 95% confidence interval: 0.74 to 0.95; p = 0.006). The addition of radiation to chemotherapy for patients with es sclc showed mixed results. There was no conclusive evidence that the timing, dose, or schedule of thoracic radiation affected treatment outcomes in sclc.Conclusions In patients with ls sclc, cisplatin–etoposide plus radiotherapy should remain the standard therapy. In patients with es sclc, the evidence is insufficient to recommend the addition of radiotherapy to chemotherapy as standard practice to improve overall survival. However, on a case-by-case basis, radiotherapy might be added to reduce local recurrence. The most commonly used chemotherapy is platinum–etoposide; however, platinum– irinotecan can be considered.

scholarly journals Survival and Toxicity After Cisplatin Plus Etoposide Versus Carboplatin Plus Etoposide for Extensive-Stage Small-Cell Lung Cancer in Elderly Patients

2016 ◽  
Vol 12 (7) ◽  
pp. 666-673 ◽  
Author(s):  
Laura A. Hatfield ◽  
Haiden A. Huskamp ◽  
Elizabeth B. Lamont
Keyword(s):  
Lung Cancer ◽  
Health Care ◽  
Elderly Patients ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Odds Ratio ◽  
Small Cell ◽  
Small Cell Lung ◽  
First Line ◽  
Extensive Stage

Purpose: Elderly patients with cancer are under-represented in clinical trials and risk greater toxicity from chemotherapy. These patients and their physicians need better evidence to decide among guideline-recommended regimens. We test whether patients with extensive-stage small-cell lung cancer (ES SCLC) have noninferior survival and less hospital-based health care after carboplatin/etoposide compared with cisplatin/etoposide. Methods: We analyzed SEER-Medicare data for beneficiaries with ES SCLC diagnosed at age 67 years and older between 1995 and 2009. Among patients treated with first-line chemotherapy in the ambulatory setting, 831 received cisplatin/etoposide and 2,846 received carboplatin/etoposide. Propensity score matching (2:1 ratio) yielded 778 cisplatin/etoposide and 1,502 carboplatin/etoposide patients. Results: Survival was nearly identical in the two groups: 35.7 weeks for cisplatin/etoposide and 35.9 weeks for carboplatin/etoposide. The hazard ratio of 1 (95% CI, 0.91 to 1.09) excluded our prespecified threshold, indicating noninferiority. Mortality at 6 months was indistinguishable: 35% for cisplatin/etoposide and 34% for carboplatin/etoposide. After carboplatin/etoposide, patients were less likely to be admitted to a hospital (80% v 86%, P < .001) and had fewer hospitalizations (median 1 v 2, odds ratio 0.76, 95% CI, 0.65 to 0.9), ED visits (median 1 v 2, odds ratio 0.82, 95% CI, 0.7 to 0.96), and ICU stays (median 0 v 0, odds ratio 0.82, 95% CI, 0.69 to 0.99). Conclusion: First-line carboplatin/etoposide is associated with similar survival and less subsequent hospital-based health care use than cisplatin/etoposide among elderly patients with ES SCLC treated in ambulatory settings.

scholarly journals First-Line Atezolizumab plus Chemotherapy in Extensive-Stage Small-Cell Lung Cancer

2018 ◽  
Vol 379 (23) ◽  
pp. 2220-2229 ◽  
Author(s):  
Leora Horn ◽  
Aaron S. Mansfield ◽  
Aleksandra Szczęsna ◽  
Libor Havel ◽  
Maciej Krzakowski ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Small Cell Lung ◽  
First Line ◽  
Extensive Stage

Use of prophylactic cranial irradiation in patients with extensive-stage small cell lung cancer receiving immunotherapy.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e19309-e19309
Author(s):  
Daniel X. Yang ◽  
Vikram Jairam ◽  
Henry S. Park ◽  
Roy H. Decker ◽  
Anne C. Chiang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Survival Benefit ◽  
Cranial Irradiation ◽  
Prophylactic Cranial Irradiation ◽  
Small Cell ◽  
Small Cell Lung ◽  
First Line ◽  
Extensive Stage

e19309 Background: Prophylactic cranial irradiation (PCI) use is controversial in extensive-stage small cell lung cancer (ES-SCLC). In addition to lack of survival benefit of PCI compared to close MRI surveillance in a 2017 published trial, the role of PCI is being further challenged in the modern immune-oncology (IO) era. The IMpower133 trial reporting a survival benefit to atezolizumab for ES-SCLC published in 2018 did not require PCI use. Contemporary practice patterns of PCI in relation to immunotherapy are unknown. Methods: We performed a retrospective cohort analysis of patients with ES-SCLC diagnosed between January 1, 2013 to September 31, 2019 from the nationwide Flatiron Health electronic health record-derived de-identified database. First-line chemotherapy (Chemo) was defined as Chemo given alone, while first-line IO therapy was IO alone or combined with chemotherapy as initial systemic therapy. Results: The cohort included 3047 ES-SCLC patients who received first-line Chemo, and 324 patients who received first-line IO. For first-line IO patients, 268 (82.7%) received first-line atezolizumab. The use of first-line IO increased from 1.2% of patients diagnosed in 2013 to 11.3% of patients diagnosed in 2018 (p < 0.001), and 54.5% of patients diagnosed in 2019 (p < 0.001). Overall documented PCI for patients receiving either first-line IO or first-line Chemo decreased from 14.7% in 2013 to 7.0% in 2018-2019 (p < 0.001). For first-line IO patients, 23 (7.1%) had documented PCI over our study period, with 5.3% of patients diagnosed in 2018-2019 having received PCI. In contrast, for first-line Chemo patients, 428 (14.0%) received PCI over our study period, and PCI use significantly decreased from 14.8% in 2013 to 7.9% in 2018-2019 (p = 0.001). In 2018-2019, use of PCI was not significantly different between patients receiving first-line IO compared to first-line Chemo (5.3% vs 7.9%, p = 0.163). Conclusions: The use of first-line IO has significantly increased in ES-SCLC. Overall PCI rates for ES-SCLC patients decreased significantly over the study period, although documented PCI use rates do not differ between patients receiving upfront IO or Chemo in 2018-2019. Further investigation is warranted regarding effectiveness of PCI in the modern IO era.

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