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Frontiers in Oncology 2023It remains unclear what the best second-line treatment is for patients with small-cell lung cancer sensitive to previous platinum-based chemotherapy.
Comparison of the second-line treatments for patients with small cell lung cancer sensitive to previous platinum-based chemotherapy: A systematic review and Bayesian network analysis.
OBJECTIVE
It remains unclear what the best second-line treatment is for patients with small-cell lung cancer sensitive to previous platinum-based chemotherapy.
METHODS
We systematically screened randomized controlled trials from several online databases. The primary outcome was objective response rate (ORR), and the secondary outcomes were disease control rate (DCR), overall survival (OS), progression-free survival (PFS), and hematological complications graded 3 to 5. The efficacy of included treatments was ranked by surface under the cumulative ranking curve (SUCRA) value.
RESULTS
We included eleven trials involving 1560 patients in quantitative analysis. Triple chemotherapy containing platinum (TP, combination of cisplatin, etoposide, and irinotecan) was associated with favorable ORR (intravenous topotecan vs TP; odds ratio: 0.13, 95% CI:0.03-0.63; SUCRA, 0.94) and PFS (vs intravenous topotecan; hazard ratio, 0.5; 95% CI: 0.25-0.99; SUCRA, 0.90). Belotecan ranked highest for OS (SUCRA, 0.90), while intravenous topotecan plus Ziv-aflibercept ranked highest for DCR (SUCRA, 0.75). TP was more likely to cause anemia and thrombocytopenia while intravenous topotecan plus Ziv-aflibercept resulted in most neutrocytopenia.
CONCLUSION
TP is the first recommendation for the second-line treatment of sensitive relapsed SCLC. TP achieved priority in ORR and PFS with the most frequent adverse effects in anemia and thrombocytopenia. For patients who cannot tolerate the hematological adverse effects of triple chemotherapy, amrubicin is an optional option. Amrubicin had relatively good ORR and PFS, accompanied by fewer hematological complications. The rechallenge of the platinum doublet is inferior to amrubicin in ORR, DCR, and PFS. Oral topotecan has a similar effect compared with IV topotecan, but oral topotecan was associated with slightly higher safety and less stress in nursing. Belotecan contributed to the best PFS with slightly better safety but was not ideal in other outcomes.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42022358256.
PubMed: 37007093
DOI: 10.3389/fonc.2023.1154685 -
Lung Cancer (Amsterdam, Netherlands) Jun 2021Optimal second-line chemotherapy for patients with relapsed small-cell lung cancer remains debatable. In addition to topotecan or amrubicin monotherapy, re-challenge... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Optimal second-line chemotherapy for patients with relapsed small-cell lung cancer remains debatable. In addition to topotecan or amrubicin monotherapy, re-challenge with first-line platinum-doublets have been commonly used. In this study, we investigated whether platinum-doublets are suitable as second-line treatment for relapsed small-cell lung cancer.
MATERIALS AND METHODS
Studies that enrolled relapsed small-cell lung cancer and compared platinum-doublets with non-platinum-based regimens for second-line treatment were identified using PubMed and EMBASE. A meta-analysis was conducted to calculate the relative risk of objective response rate and disease control rate of the second-line chemotherapy. Subgroup analyses were conducted to focus on comparison with standard second-line regimens and sensitive relapse. Progression-free and overall survival, and adverse events were systematically reviewed.
RESULTS
Ten studies published between 2011 and 2020 were included in our analysis with a total of 1222 patients: 438 treated with platinum-doublets and 784 with non-platinum-based regimens. The objective response rates for second-line platinum-doublet and non-platinum regimens were 47.3 % [95 % CI: 40.5-54.0] and 31.5 % [95 % CI: 22.2-40.8], respectively. Patients treated with platinum-doublets had a significantly higher objective response rate than patients with non-platinum-based regimens (RR [95 % CI]: 1.527 [1.100-2.121], p = 0.011), as well as disease control rate (RR [95 % CI]: 1.152 [1.052-1.262], p = 0.002). In a subgroup analysis comparing platinum-doublets with topotecan or amrubicin, patients treated with platinum-doublets had significantly higher objective response rate and disease control rate (RR [95 % CI]: 1.663 [1.055-2.619], p = 0.028 and 1.170 [1.021-1.340], p = 0.023 respectively). Progression-free and overall survival appeared consistent with the tumor responses. Adverse events associated with platinum-doublets appeared acceptable compared with the monotherapies.
CONCLUSION
Platinum-doublet chemotherapy as second-line treatment for patients with relapsed small-cell lung cancer can be considered as a reasonable option in comparison with non-platinum regimens.
Topics: Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Humans; Lung Neoplasms; Neoplasm Recurrence, Local; Small Cell Lung Carcinoma
PubMed: 33894495
DOI: 10.1016/j.lungcan.2021.04.013 -
Current Oncology (Toronto, Ont.) Feb 2021Improving therapeutic strategies for extensive-stage small cell lung cancer (ES-SCLC) remains a challenge. To date, no reports have directly compared the efficacy and... (Meta-Analysis)
Meta-Analysis Review
Comparative Efficacy and Safety of Immunotherapeutic Regimens with PD-1/PD-L1 Inhibitors for Previously Untreated Extensive-Stage Small Cell Lung Cancer: A Systematic Review and Network Meta-Analysis.
Improving therapeutic strategies for extensive-stage small cell lung cancer (ES-SCLC) remains a challenge. To date, no reports have directly compared the efficacy and safety of immune checkpoint inhibitors plus platinum-etoposide (ICIs+EP) with platinum-irinotecan (IP) or directly compared different ICIs+EP for previously untreated ES-SCLC. This study used a Bayesian approach for network meta-analysis to compare efficacy and safety between ICIs+EP and IP and between each pair of three ICIs+EP. The six treatment arms were: pembrolizumab plus platinum-etoposide (Pem+EP), durvalumab plus platinum-etoposide (Dur+EP), atezolizumab plus platinum-etoposide (Atz+EP), platinum-amrubicin (AP), IP, and platinum-etoposide (EP). No significant differences in overall survival were observed between ICIs+EP and IP and between each pair of three ICIs+EP. The incidence of ≥grade 3 adverse events (G3-AEs) was significantly higher in ICIs+EP than IP, whereas no significant difference was found in G3-AEs between each pair of three ICIs+EP. The incidence of ≥grade 3 neutropenia and thrombocytopenia was significantly higher in ICIs+EP than IP, whereas the incidence of ≥grade 3 diarrhea was significantly lower in ICIs+EP than IP. These findings will help clinicians better select treatment strategies for ES-SCLC.
Topics: Antineoplastic Combined Chemotherapy Protocols; Bayes Theorem; Humans; Immune Checkpoint Inhibitors; Immunotherapy; Lung Neoplasms; Network Meta-Analysis; Programmed Cell Death 1 Receptor; Small Cell Lung Carcinoma
PubMed: 33673470
DOI: 10.3390/curroncol28020106 -
Therapeutic Advances in Medical Oncology 2020Our goal was to organize the data from randomized controlled trials that evaluated first-line chemotherapy for chemo-naïve extensive disease small-cell lung cancer...
BACKGROUND
Our goal was to organize the data from randomized controlled trials that evaluated first-line chemotherapy for chemo-naïve extensive disease small-cell lung cancer (ED-SCLC).
METHODS
The protocol following PRISMA methodology was submitted as PROSPERO 154049. We included individually randomized trials comparing two or more chemotherapy regimens as the first-line treatment for chemo-naïve ED-SCLC regardless of the age, sex, performance status, co-morbidities, and organ functions written in the English language since 2000. Molecular targeted agents and immune checkpoint inhibitors were considered chemotherapy along with cytotoxic medications. We pooled the logarithm of hazard ratio (HR) and its standard error using the frequentist weighted least squares approach random-model network meta-analysis.
RESULTS
A total of 46 eligible trials that involved 11,987 patients were included. The primary endpoint, HR of overall survival (OS, HRos) of the selected comparisons was as follows: carboplatin+amrubicin (HRos 0.56, 95% confidence interval (CI) 0.33-0.96), carboplatin+etoposide+atezolizumab (HRos 0.70, 95% CI 0.53-0.92), and carboplatin+irinotecan (HRos 0.73, 95% CI 0.58-0.91) were compared with carboplatin+etoposide. The carboplatin+etoposide+atezolizumab regimen was compared with carboplatin+irinotecan (HRos 0.97, 95% CI 0.68-1.37) and cisplatin+irinotecan regimen (HRos 0.87, 95% CI 0.58-1.31). "Selective carboplatin or cisplatin (CBDCA/CDDP)"+etoposide+durvalumab was compared with CBDCA/CDDP+etoposide (HRos 0.73, 95% CI 0.59-0.91). Platinum+etoposide+durvalumab was compared with platinum+irinotecan (HRos 0.88, 95% CI 0.67-1.15). Cumulative meta-analysis suggested that platinum+irinotecan was associated with better OS than platinum+etoposide as of 2010 through 40 out of 46 trials in our review that used platinum+etoposide as a reference regimen.
CONCLUSION
Patients treated with carboplatin+amrubicin, carboplatin+etoposide+atezolizumab, CBDCA/CDDP+etoposide+durvalumab, and platinum+irinotecan showed better HRos than those treated with platinum+etoposide, one of the standard regimens.
PubMed: 33403010
DOI: 10.1177/1758835920965841 -
Therapeutic Advances in Medical Oncology 2020There is no standard second-line treatment for patients with advanced extra-pulmonary poorly differentiated neuroendocrine carcinoma (EP-PD-NEC). This study explored... (Review)
Review
BACKGROUND
There is no standard second-line treatment for patients with advanced extra-pulmonary poorly differentiated neuroendocrine carcinoma (EP-PD-NEC). This study explored data evaluating second-line treatment in these patients.
METHODS
A search of MEDLINE and EMBASE identified studies reporting survival and/or response data for patients with EP-PD-NEC receiving second-line therapy. Association between various factors (age, gender, ECOG performance status, primary tumour location, morphology, Ki-67, treatment and grade 3/4 haematological toxicity) and response rate (RR), progression-free (PFS) and overall survival (OS) were assessed with a mixed effects meta-regression weighted by individual study sample size. Due to a small sample size, associations were reported quantitatively, based on magnitude of beta coefficient rather than statistical significance.
RESULTS
Of 83 identified studies, 19 were eligible, including 4 prospective and 15 retrospective studies. Analysis comprised 582 patients, with a median number of 19 patients in each study (range 5-100). Median age was 59 years (range 53-66). Median RR was 18% (range 0-50; 0% for single-agent everolimus, temozolomide, topotecan; 50% with amrubicin), median PFS was 2.5 months (range 1.15-6.0) and median OS was 7.64 months (range 3.2-22.0). Studies with a higher proportion of patients with a Ki-67>55% had lower RR (β = -0.73) and shorter OS (β = -0.82).
CONCLUSION
Second-line therapy for patients with advanced EP-PD-NEC has limited efficacy and the variety of regimens used is diverse. Ki-67>55% is associated with worse outcomes. Prospective randomised studies are warranted to enable exploration of new treatment strategies.
PubMed: 32426044
DOI: 10.1177/1758835920915299