Extensive-stage Small Cell Lung Cancer Research Articles

Predictive Signatures for Responses to Checkpoint Blockade in Small-Cell Lung Cancer in Second-Line Therapy Do Not Predict Responses in First-Line Patients.

Although immune checkpoint blockade (ICB) is currently approved for the treatment of extensive-stage small-cell lung cancer (SCLC) in combination with chemotherapy, relatively few patients have demonstrated durable clinical benefit (DCB) to these therapies. Biomarkers predicting responses are needed. Biopsies from 35 SCLC patients treated with ICB were subjected to transcriptomic analysis; gene signatures were assessed for associations with responses. Twenty-one patients were treated with ICB in the first-line setting in combination with platinum-based chemotherapy; fourteen patients were treated in the second-line setting with ICB alone. DCB after ICB in SCLC in the second-line setting (3 of 14 patients) was associated with statistically higher transcriptomic levels of genes associated with inflammation (p = 0.003), antigen presentation machinery (p = 0.03), interferon responses (p < 0.05), and increased CD8 T cells (p = 0.02). In contrast, these gene signatures were not significantly different in the first-line setting. Our data suggest that responses to ICB in SCLC in the second-line setting can be predicted by the baseline inflammatory state of the tumor; however, this strong association with inflammation was not seen in the first-line setting. We postulate that chemotherapy alters the immune milieu allowing a response to ICB. Other biomarkers will be needed to predict responses in first-line therapy patients.

Evaluation of Efficacy and Safety in First-Line Treatment Methods for Extensive-Stage Small Cell Lung Cancer: A Comprehensive Comparative Study of Chemotherapy, Targeted Therapy Combined With Chemotherapy, and Immunotherapy Combined With Chemotherapy.

Small cell lung cancer (SCLC) is a highly aggressive tumor with limited effectiveness in its standard chemotherapy treatment. Targeted antiangiogenic therapy and immune checkpoint inhibitors (ICIs) have demonstrated potential as alternative treatments for extensive-stage SCLC (ES-SCLC). However, there is insufficient comparative evidence available to determine the optimal first-line treatment option between ICIs plus chemotherapy and targeted antiangiogenic therapy plus chemotherapy. This study is aimed at analyzing clinical data from ES-SCLC patients treated at the First Affiliated Hospital of Bengbu Medical College between June 2021 and June 2023. The study compared the efficacy and safety of three first-line treatment regimens: standard chemotherapy, antiangiogenic therapy combined with chemotherapy, and immune combination therapy. Patients who met the inclusion criteria were divided into three groups: chemotherapy, immune combination therapy, and antiangiogenic therapy combined with chemotherapy. The study collected data on clinical characteristics, treatment regimens, and adverse reactions. The analysis included objective response rate (ORR), duration of response (DoR), disease control rate (DCR), progression-free survival (PFS), and treatment safety. A total of 101 patients were included in the study, with 49 receiving chemotherapy alone, 19 receiving antiangiogenic therapy, and 33 receiving immune combination therapy. The ORRs were 78.9% for antiangiogenic therapy, 72.7% for immune combination therapy, and 42.9% for chemotherapy alone. The median PFS was 8.0 months for antiangiogenic therapy, 7.8 months for immune combination therapy, and 5.2 months for chemotherapy alone. Both combination therapy groups demonstrated superior efficacy compared to chemotherapy alone. Targeted combined chemotherapy and immune combination chemotherapy showed superior efficacy as first-line treatments for ES-SCLC compared to chemotherapy alone, with manageable adverse reactions.

DARES: A Phase II Trial of Durvalumab and Ablative Radiation in Extensive-Stage Small Cell Lung Cancer

Immunotherapy in combination with chemotherapy is first-line treatment for patients with extensive-stage small-cell lung cancer (ES-SCLC). Growing evidence suggests that radiation, specifically stereotactic body radiation therapy (SBRT), may enhance the immunogenic response as well as cytoreduce tumor burden. The primary objective of the study is to determine the progression free survival for patients with newly diagnosed ES-SCLC treated with combination multisite SBRT and chemo-immunotherapy (carboplatin, etoposide, and durvalumab). This is a multicenter, single arm, phase 2 study. Patients with treatment-naïve, ES-SCLC will be eligible for this study. Patients will receive durvalumab 1500mg IV q3w, carboplatin AUC 5 to 6 mg/mL q3w, and etoposide 80 to 100 mg/m2 on days 1 to 3 q3w for four cycles, followed by durvalumab 1500mg IV q4w until disease progression or unacceptable toxicity. Ablative radiation will be delivered 1 to 4 extracranial sites in 3 or 5 fractions, determined by location, during cycle 2. The primary endpoint is progression-free survival, measured from day 1 of chemoimmunotherapy. Secondary endpoints include grade ≥3 toxicity by CTCAE v5.0 within three months of RT, overall survival, response rate, time to second line systemic therapy, and time to new distant progression. Now that immunotherapy is an established part of ES-SCLC management, it is important to further optimize its use and effect. This study will investigate the progression-free survival of combined SBRT and chemo-immunotherapy in patients with ES-SCLC. In addition, the data from this study may further inform the immunogenic role of SBRT with chemo-immunotherapy, as well as identify clinical, biological, or radiomic prognostic features.

Effectiveness and safety of anlotinib plus anti-programmed cell death 1/ligand 1 (anti-PD-1/PD-L1) antibodies as maintenance therapy after first-line chemotherapy combined with anti-PD-1/PD-L1 antibodies in extensive-stage small cell lung cancer: a real-world study.

Currently, chemotherapy plus immunotherapy followed by maintenance therapy with immune monotherapy is the preferred first-line treatment option for extensive-stage small cell lung cancer (ES-SCLC), but with limited overall survival (OS) and progression-free survival (PFS) benefits. The combination of anti-angiogenic drugs with immunotherapy has shown encouraging anti-tumor activity and tolerability, with some degree of overcoming immune resistance. This study aimed to evaluate the effectiveness and safety of anlotinib plus anti-programmed cell death 1/ligand 1 (anti-PD-1/PD-L1) antibodies as maintenance therapy after first-line chemotherapy combined with immunotherapy in ES-SCLC. Between June 2020 and December 2021, 12 patients with newly diagnosed ES-SCLC in the First Affiliated Hospital of Army Medical University were retrospectively analyzed. All patients without disease progression after 4-6 cycles of first-line platinum-containing chemotherapy plus anti-PD-1/PD-L1 antibodies received anlotinib (12 mg oral/day, days 1-14, followed by 1 week off, every 3 weeks per cycle) plus anti-PD-1/PD-L1 antibodies as maintenance therapy. Several patients underwent chest radiotherapy (intensity-modulated radiotherapy using a 6 MV X-ray) without disease progression before maintenance therapy. The effectiveness and safety of anlotinib plus anti-PD-1/PD-L1 antibodies as maintenance therapy after first-line chemotherapy combined with immunotherapy in ES-SCLC were evaluated. The median follow-up time was 31.1 months. During first-line treatment (including maintenance therapy), one patient achieved a complete response, eight patients achieved a partial response (PR), and three patients had stable disease, with an objective response rate of 75.0% and a disease control rate of 100.0%. During maintenance therapy with anlotinib plus anti-PD-1/PD-L1 antibodies, 50.0% of patients achieved further lesion remission on the basis of the prior initial treatment, of which one patient achieved a PR. The median PFS was 13.6 [95% confidence interval (CI): 11.2-15.6] months, and the median OS was 19.5 (95% CI: 14.5-24.5) months. Treatment-related any grade and grade 3-4 adverse events (AEs) were reported in 100.0% and 58.3% of patients, respectively. No life-threatening AEs were observed. Grade 3-4 AEs included leukocytopenia (58.3%, 7/12), thrombocytopenia (33.3%, 4/12), nausea (33.3%, 4/12), anemia (16.7%, 2/12), and fatigue (8.3%, 1/12). All AEs during maintenance therapy were tolerated and were regarded as grade 1-2, with the majority being fatigue, nausea, rash, and hemoptysis. The combination of anlotinib with anti-PD-1/PD-L1 antibodies demonstrated encouraging effectiveness and safety in treating patients with ES-SCLC, suggesting that it may be a preferred option for maintenance therapy after first-line chemotherapy combined with immunotherapy.

Efficacy of Apatinib Combined with Etoposide for Maintenance Therapy in Extensive Stage Small Cell Lung Cancer

Objective: To investigate the efficacy, safety and survival of apatinib combined with etoposide for maintenance therapy in extensive stage small cell lung cancer (ES-SCLC). Method: A total of 70 patients with extensive stage small cell lung cancer after standard chemo-radiotherapy who were admitted to Tangshan people’s Hospital from January 2019 to February 2023 were enrolled and then grouped into the observation group and the control group by random number table method, with 35 patients in each group. Patients from the observation group received apatinib combined with oral etoposide capsules for maintenance therapy. Patients from the control group received etoposide capsules for maintenance chemotherapy. The clinical efficacy and adverse reactions of these two groups were compared, and the 6-month and 1-year survivals were followed up. Results: The objective response rate (ORR) and disease control rate (ODC) of the observation group were higher than those of the control group [37.1% (13 / 35) vs. 17.1% (6 / 35), 65.7% (23 / 35) vs. 40% (14 / 35)], and the differences were statistically significant (all p&lt;0.05). There was no significant difference in the incidence of adverse reactions between these two groups (p&gt;0.05). The 6-month and 1-year survival rates of the observation group were significantly higher than those of the control group, and the differences were statistically significant (all p&lt;0.05). Conclusion: Apatinib combined with etoposide capsules applied for maintenance therapy in extensive stage small cell lung cancer could provide improved clinical efficacy and survival rate of patients, with tolerable adverse reactions.

Navigating first-line therapies for extensive-stage small-cell lung cancer: a frequentist network meta-analysis and systematic review.

Aim: To identify the optimal first-line treatment for patients with extensive-stage small-cell lung cancer (ES-SCLC).Materials & methods: We conducted a network meta-analysis (CRD42023486863) to systematically evaluate the efficacy and safety of eight first-line treatment regimens for ES-SCLC, including 15 clinical trials.Results: Our analysis showed that the PD-1/PD-L1+ etoposide combined withplatinum (EP)and PD-L1+ vascular endothelial growth factor (VEGF) +EP regimens significantly enhanced overall survival and progression-free survival, with subgroup analysis revealing that serplulimab ranked as the most promising option for improving overall survival. Integrating anti-angiogenesis drugs into immunochemotherapy presents potential benefits, with an increased incidence of adverse events necessitating further investigation.Conclusion: Our findings offer valuable insights for future research and for developing more effective treatment strategies for ES-SCLC, underscoring the critical need for continued innovation in this therapeutic area.

Efficacy and safety of G-CSF prophylaxis in patients with extensive-stage small cell lung cancer receiving chemoimmunotherapy

ABSTRACT Objectives We aimed to evaluate the efficacy and safety of granulocyte-colony stimulating factor (G-CSF) prophylaxis during chemoimmunotherapy with carboplatin plus etoposide and atezolizumab in extensive-stage small cell lung cancer (ES-SCLC). Methods This retrospective, multicenter study enrolled ES-SCLC patients receiving carboplatin plus etoposide and atezolizumab, categorized into G-CSF and non-G-CSF groups. Demographic and disease-related data were collected. Response rates, progression-free survival (PFS), overall survival (OS), and toxicity were analyzed. Results Of 119 patients (median age: 63 years), the overall response rate (ORR) and disease control rate (DCR) were 72.3% and 81.5%, respectively. In the G-CSF group, the ORR was 76.4% compared to 60.0% in the non-G-CSF group (p = 0.33), and the DCR was 85.4% versus 70.0%, respectively (p = 0.46). Median PFS was 8.3 months (95% CI, 6.8–9.8) in the G-CSF group and 6.8 months (95% CI, 6.2–7.5) in the non-G-CSF group (p = 0.24). Median OS was 13.8 months (95% CI, 9.6–18.1) for the G-CSF group and 10.6 months (95% CI, 7.9–13.3) for the non-G-CSF group (p = 0.47). Grade 3 ≥ adverse events were similar between groups (49.4% vs. 33.3%, respectively, p = 0.12). Conclusion G-CSF prophylaxis can be safely used in ES-SCLC patients undergoing carboplatin plus etoposide and atezolizumab regimen without significantly altering efficacy or increasing toxicity.

Tarlatamab: First Approval.

Tarlatamab (tarlatamab-dlle: IMDELLTRA™) is a first-in-class, half-life extended bispecific delta-like ligand 3 (DLL3)-directed CD3 T-cell engager being developed by Amgen for the treatment of small cell lung cancer (SCLC) and neuroendocrine prostate cancer. Tarlatamab binds to DLL3 on the surface of tumour cells and CD3 on the surface of cytotoxic T lymphocytes (CTLs), resulting in T-cell activation, release of inflammatory cytokines and CTL-mediated cell death of DLL3-expressing tumour cells. In May 2024, tarlatamab received its first approval in the USA for the treatment of adults with extensive stage SCLC (ES-SCLC) with disease progression on or after platinum-based chemotherapy. Tarlatamab received accelerated approval for this indication based on overall response rate and duration of response in the pivotal phase 2 DeLLphi-301 study, and continued approval may be contingent on the demonstration of clinical benefit in a confirmatory trial(s). Tarlatamab is under regulatory review in Brazil, Canada, Israel and the UK, and clinical studies are underway in multiple countries. This article summarizes the milestones in the development of tarlatamab leading to this first approval for ES-SCLC with disease progression on or after platinum-based chemotherapy.

Novel Combinations of Immunotherapies or DNA Damage Repair Inhibitors in Platinum-Refractory Extensive-Stage Small Cell Lung Cancer: The Phase II BALTIC Study.

The phase II, multiarm, signal-searching BALTIC study (NCT02937818) assessed novel treatment combinations for platinum-refractory/resistant extensive-stage small cell lung cancer (ES-SCLC). Patients with ES-SCLC with progressive disease during or within 90 days of completing first-line platinum-based chemotherapy received one of three regimens: durvalumab plus tremelimumab followed by durvalumab monotherapy (arm A), adavosertib plus carboplatin (arm B), or ceralasertib plus olaparib (arm C). The primary endpoint was the objective response rate. Prespecified exploratory biomarker analyses were conducted in arms A and C. In arm A (n = 41), arm B (n = 10), and arm C (n = 21), the confirmed objective response rates were 7.3%, 0%, and 4.8%, respectively. Safety profiles in all arms were consistent with those of the individual drugs. In arm A, patients with PD-L1 expression (tumor cells or immune cells) ≥1% seemed to have a greater likelihood of achieving disease control with durvalumab plus tremelimumab than those with PD-L1 (tumor cells and immune cells) <1%, and lower baseline ctDNA and reduction in the on-treatment ctDNA level were both associated with longer overall survival. Among patients treated with ceralasertib plus olaparib in arm C, specific immune response-relevant circulating chemokines and cytokines were identified as early biomarkers of survival and pharmacodynamic biomarkers. In BALTIC, all combination regimens demonstrated tolerable safety profiles, but antitumor activity was limited in refractory/resistant ES-SCLC. Among patients treated with durvalumab plus tremelimumab, an association of on-treatment reduction in ctDNA with longer overall survival suggests the potential use of ctDNA as a surrogate of treatment response, warranting further investigation.

Granulocyte colony-stimulating factor has the potential to attenuate the therapeutic efficacy of chemo-immunotherapy for extensive-stage small-cell lung cancer.

Granulocyte colony-stimulating factor (G-CSF) has the potential to attenuate the anti-tumor immune responses of T-cells by increasing immune suppressive neutrophils and myeloid-derived suppressor cells. However, the clinical impact of G-CSF on the efficacy of immunotherapy remains unknown. This multi-center retrospective analysis evaluated the impact of G-CSF in patients with extensive-stage small-cell lung cancer (ES-SCLC) treated with chemo-immunotherapy. We analyzed 65 patients with ES-SCLC who completed four cycles of induction chemo-immunotherapy and evaluated the effects of G-CSF on progression-free survival (PFS), overall survival (OS), and a durable response to immunotherapy (defined as PFS ≥ 12months). Fifty patients (76.9%) received ≥ 1 dose of G-CSF. The PFS of the patients with G-CSF was poorer than that of the patients without G-CSF (median PFS 8.3 vs. 4.9months, p = 0.009). The OS of the patients with G-CSF tended to be shorter, but not statistically significant, than that of the patients without G-CSF (median OS 24.3 vs. 16.4months, p = 0.137). In the multivariate analysis, G-CSF administration was associated with poorer PFS (hazard ratio 2.78, 95% CI 1.36-5.69, p = 0.005) and was identified as a determinant of a durable response (odds ratio 0.18, 95% CI 0.04-0.80, p = 0.024). These results were consistent with other definitions of G-CSF administration (administration of ≥ 1 dose of pegfilgrastim, or either ≥ 5 doses of filgrastim or ≥ 1 dose of pegfilgrastim). G-CSF has the potential to attenuate the efficacy of immunotherapy; therefore, the indication for G-CSF during chemo-immunotherapy should be carefully considered for ES-SCLC.

Benmelstobart, anlotinib and chemotherapy in extensive-stage small-cell lung cancer: a randomized phase 3 trial

Immunochemotherapy is the first-line standard for extensive-stage small-cell lung cancer (ES-SCLC). Combining the regimen with anti-angiogenesis may improve efficacy. ETER701 was a multicenter, double-blind, randomized, placebo-controlled phase 3 trial that investigated the efficacy and safety of benmelstobart (a novel programmed death-ligand 1 (PD-L1) inhibitor) with anlotinib (a multi-target anti-angiogenic small molecule) and standard chemotherapy in treatment-naive ES-SCLC. The ETER701 trial assessed two primary endpoints: Independent Review Committee-assessed progression-free survival per RECIST 1.1 and overall survival (OS). Here the prespecified final progression-free survival and interim OS analysis is reported. Patients randomly received benmelstobart and anlotinib plus etoposide/carboplatin (EC; n = 246), placebo and anlotinib plus EC (n = 245) or double placebo plus EC (‘EC alone’; n = 247), followed by matching maintenance therapy. Compared with EC alone, median OS was prolonged with benmelstobart and anlotinib plus EC (19.3 versus 11.9 months; hazard ratio 0.61; P = 0.0002), while improvement of OS was not statistically significant with anlotinib plus EC (13.3 versus 11.9 months; hazard ratio 0.86; P = 0.1723). The incidence of grade 3 or higher treatment-related adverse events was 93.1%, 94.3% and 87.0% in the benmelstobart and anlotinib plus EC, anlotinib plus EC, and EC alone groups, respectively. This study of immunochemotherapy plus multi-target anti-angiogenesis as first-line treatment achieved a median OS greater than recorded in prior randomized studies in patients with ES-SCLC. The safety profile was assessed as tolerable and manageable. Our findings suggest that the addition of anti-angiogenesis therapy to immunochemotherapy may represent an efficacious and safe approach to the management of ES-SCLC. ClinicalTrials.gov identifier: NCT04234607.

Camrelizumab combined with anlotinib as second-line therapy for metastatic or recurrent small cell lung cancer: a retrospective cohort study.

This retrospective study evaluates the efficacy of camrelizumab combined with anlotinib versus chemotherapy in patients with extensive-stage small-cell lung cancer (ES-SCLC) undergoing second-line treatment. Data were sourced from medical records at a Chinese medical facility, involving 34 patients diagnosed with ES-SCLC after failing first-line treatment. Patients were divided into two groups: one received camrelizumab (200 mg every 3 weeks) with anlotinib (12 mg daily for 14 days followed by a 7-day rest), while the other group received physician-chosen chemotherapy administered every 3 weeks. The primary endpoint was progression-free survival (PFS), with secondary endpoints including overall survival (OS), objective response rate (ORR), and disease control rate (DCR). The combination therapy group showed a significant improvement in PFS compared to the chemotherapy group (median PFS: 7 months vs. 3 months; hazard ratio (HR): 0.34; 95% confidence interval (CI): 0.15-0.77; p<0.001). However, there was no statistically significant difference in OS between the groups (16.3 months vs. 17.3 months; p=0.82). The ORR was 52.9% in the combination therapy group versus 23.5% in the chemotherapy group (p=0.08), and the DCR was 82.4% compared to 58.8% (p=0.26). Grade 3 or higher adverse events were observed in 17.6% of the combination therapy group and 29.4% of the chemotherapy group. The findings suggest that the combination of camrelizumab and anlotinib offers a superior anti-tumor response with a manageable safety profile in a second-line setting for ES-SCLC patients. This combination regimen may be a viable option for second-line ES-SCLC treatment.

Second-line treatment outcomes after first-line chemotherapy plus immunotherapy in Extensive-Stage small cell lung cancer (ES-SCLC) patients: A large French multicenter study

IntroductionChemotherapy combined with immunotherapy (CT-IO) is the standard treatment for patients with Extensive-Stage Small Cell Lung Cancer (ES-SCLC). This study evaluates the effectiveness of second-line (2L) following CT-IO. Patients and MethodsAll patients from 10 centers who received a 2L after a first-line CT-IO were included. They were divided into 3 groups: platinum-based, lurbinectedin or others (topotecan, CAV, taxanes). We assessed overall survival (OS) and 2L progression-free survival (2L-PFS) according to treatment and platinum free-interval (PFI) < or ≥ 90 days. ResultsAmong 82 patients included, median age was 67.0 years, 29.3 % had a Performans Status ≥ 2, 36.6 % had brain progression, 69.5 % were considered “platine-sensitive” and 30.5 % “platine-resistant” (PFI ≥ or < 90 days, respectively). As 2L, 37/82 patients (45.1 %) received platinum-doublet, 21/82 (25.6 %) lurbinectedin and 24/82 (29.3 %) others. Patients with a PFI ≥ 90 days received mainly platinum-based rechallenge (34/57, 59.6 %). With a median follow-up of 18.5 months, the median OS was 5.0 months (95 %CI, 1.5–7.9) / 6.8 months (95 %CI, 5.5–8.7) for platinum-resistant / sensitive, respectively (log rank p = 0.017). The median 2L-PFS was 1.9 months (95 %CI, 1.2–4.7) / 3.9 months (95 %CI, 2.9–6.0) for platinum-resistant / sensitive, respectively. Median OS was 8.1 (95 %CI, 6.3–12.9) / 4.9 (95 %CI, 3.7–6.8) / 5.1 months (95 %CI, 2.5–7.8) with platinum rechallenge / lurbinectedin / others, respectively (p = 0.017). Median 2L-PFS was 4.6 (95 %CI, 3.9–7.2) / 2.7 (95 %CI, 1.6–3.9) / 2.2 months (95 %CI, 1.5–4.1) with platinum rechallenge / lurbinectedin / others, respectively (p = 0.025). DiscussionPlatinum-based rechallenge after a first-line CT-IO showed promising results despite particularly unfavorable characteristics within our real-word population. Lurbinectedin when used after IO demonstrated as low efficacy as other platinum-free regimens.

Preclinical study and phase II trial of adapting low-dose radiotherapy to immunotherapy in small cell lung cancer

Immune checkpoint inhibitors (ICIs) provide modest but unsatisfactory benefits for extensive-stage small cell lung cancer (ES-SCLC). Developing strategies for treating ES-SCLC is critical. We preliminarily explored the outcomes of salvage low-dose radiotherapy (LDRT) plus ICI on refractory SCLC patients. Next, we evaluated the combinational efficacy in murine SCLC. The tumor immune microenvironment (TIME) was analyzed for mechanistic study. Subsequently, we conducted a multicenter, prospective phase II trial that administered concurrent thoracic LDRT plus chemoimmunotherapy to treatment-naive ES-SCLC patients (MATCH trial, NCT04622228). The primary endpoint was confirmed objective response rate (ORR), and the key secondary endpoints included progression-free survival (PFS) and safety. Fifteen refractory SCLC patients treated with LDRT plus ICI were retrospectively reviewed. The ORR was 73.3% (95% confidence interval [CI], 44.9-92.2). We identified a specific dose of LDRT (15 Gy/5 fractions) that exhibited growth retardation and improved survival in murine SCLC when combined with ICIs. This combination recruited a special Tcell population, TCF1+ PD-1+ CD8+ stem-like Tcells, from tumor-draining lymph nodes into the TIME. The MATCH trial showed a confirmed ORR of 87.5% (95% CI, 75.9-94.8). The median PFS was 6.9months (95% CI, 5.4-9.3). These findings verified that LDRT plus chemoimmunotherapy was safe, feasible, and effective for ES-SCLC, warranting further investigation. This research was funded by West China Hospital (no. ZYJC21003), the National Natural Science Foundation of China (no. 82073336), and the MATCH trial was fully funded by Roche (China) Holding Ltd. (RCHL) and Shanghai Roche Pharmaceuticals Ltd. (SRPL).

Which Is More Suitable for First-Line Treatment of Extensive-Stage Small Cell Lung Cancer, PD-L1 Inhibitors Versus PD-1 Inhibitors? A Systematic Review and Network Meta-Analysis.

In this network meta-analysis (NMA), the efficiency and safety of PD-1 inhibitors + chemotherapy and PD-L1 inhibitors + chemotherapy were compared in the first-line therapy of patients with extensive-stage small cell lung cancer (ES-SCLC). We searched research databases, conference abstracts, and trial registries and subsequently chose relevant studies and extracted dates. The NMA was conducted to estimate the efficiency and safety of the PD-1 inhibitors + chemotherapy and PD-L1 inhibitors + chemotherapy on overall survival (OS), progression-free survival (PFS), overall remission rate (ORR), and adverse events (AEs). Studies were assessed for quality. Subgroup analyses were used to evaluate study heterogeneity. We included six randomized trials with a total of 3163 patients. Direct comparisons showed that patients who received either PD-1 inhibitors + chemotherapy (HR: 0.71, 95% CI: 0.57-0.87) or PD-L1 inhibitors + chemotherapy (HR: 0.74, 0.61-0.89) demonstrated significantly longer OS than those who received placebo + chemotherapy. The results of the NMA showed that no significant differences in OS (HR 0.96 95% CI: 0.72-1.3), PFS (HR 0.83, 95% CI: 0.51-1.4), and ORR (OR 1.3 95% CI: 0.66-2.5) were observed for PD-1 inhibitors + chemotherapy compared with PD-L1 inhibitors + chemotherapy, but the Bayesian ranking revealed that patients receiving PD-1 inhibitors + chemotherapy tended to have longer OS, PFS benefit, and better treatment response than patients receiving PD-L1 inhibitors + chemotherapy. In terms of safety, no significant difference was observed in their safety profiles. In comparison to placebo + chemotherapy, PD-L1 inhibitors + chemotherapy and PD-1 inhibitors + chemotherapy significantly improved survival for ES-SCLC. According to the available data, PD-L1 inhibitors + chemotherapy and PD-1 inhibitors + chemotherapy had equivalent efficacy and safety; however, the level of evidence of this type of comparison is limited.

Real-world comparison of chemo-immunotherapy and chemotherapy alone in the treatment of extensive-stage small-cell lung cancer

Small cell lung cancer (SCLC) is a high-grade neuroendocrine carcinoma responsible for 200,000 deaths per year worldwide. Platinum-etoposide-based chemotherapy has been the standard of treatment for the past 40 years, with an overall survival of 10 months. Since 2019, the addition of immunotherapy (atezolizumab or durvalumab) to chemotherapy has become the standard of care for first-line treatment of extensive-stage SCLC following the demonstration of an improvement in overall survival in phase 3 studies. We aimed to evaluate the efficacy and safety of chemo-immunotherapy compared with chemotherapy alone in a "real-world" setting. Retrospective observational study including patients undergoing first-line treatment for extensive-stage SCLC between 2014 and 2022. We separated the study population into two arms (chemo-immunotherapy/chemotherapy). For each arm, progression-free survival (PFS), overall survival (OS) and serious side effects were collected. Associations between treatments and survival outcomes were adjusted for potential confounders. Consolidative palliative thoracic radiotherapy was introduced in the models as a time-dependent variable. A total of 118 patients with a median age of 63 years were included. 65.2 % of patients were performance status 0 or 1. In univariate analysis, PFS and OS were not significantly different between the chemo-immunotherapy and chemotherapy alone groups (p = 0.70 and 0.24 respectively). In multivariate analysis, the addition of immunotherapy to chemotherapy was not significantly associated with better PFS (HR 0.76, IC (0.49 - 1.19), p = 0.23), but it was significantly associated with better OS (HR 0.61, IC (0.38 - 0.98), p = 0.04). Consolidative palliative thoracic radiotherapy (time-dependent variable), when applied (almost only in the chemotherapy alone group), was significantly associated with better PFS and OS. In this real-world study, chemo-immunotherapy was associated with slightly better OS compared to chemotherapy alone as a first-line treatment in ES-SCLC patients in multivariate analysis, which is not explained by a benefit in PFS. However, consolidative palliative thoracic radiotherapy seems to be significantly associated with better OS and PFS, suggesting that we should also consider using it in patients receiving chemo-immunotherapy.

PP01.25 Burden of Chemotherapy-induced Myelosuppression on Patients with Extensive-stage Small Cell Lung Cancer (ES-SCLC) from the Perspective of Patients and Caregivers

PP01.25 Burden of Chemotherapy-induced Myelosuppression on Patients with Extensive-stage Small Cell Lung Cancer (ES-SCLC) from the Perspective of Patients and Caregivers

Treatment-related Adverse Events, Including Fatal Toxicities, in Patients With Extensive-stage Small-cell Lung Cancer Receiving Adjuvant Programmed Cell Death 1/Programmed Cell Death Ligand 1 Inhibitors: A Meta-analysis and Trial Sequential Analysis of Randomized Controlled Trials

Background/AimsThe safety profile of programmed cell death 1 (PD-1)/programmed cell death ligand 1 (PD-L1) inhibitors when associated with chemotherapy for the treatment of patients with extensive-stage small-cell lung cancer is still not fully unraveled. MethodsWe performed a comprehensive searrch of the PubMed, Embase, and Cochrane databases for randomized controlled trials that investigated the addition of PD-1 or PD-L1 inhibitors to standard investigator choice chemotherapy. We used risk -ratios (RRs) with 95% confidence intervals (CIs) for all endpoints. ResultsSix studies and 2,995 patients were included. At the baseline, the median age of the patients varied from 62 to 65 years, 311 (10.4%) had brain metastases, and 1,060 (35.4%) had liver metastases. PD-1/PD-L1 inhibitors were found to reduce fatal toxicities-related mortality (RR: 0.85; 95% CI: 0.80–0.91; p < 0.001; I2 = 49%). The intervention group had a higher incidence of decreased appetite (RR: 1.19; 95% CI: 1.02–1.40; p = 0.03; I2 = 0%), hyponatremia (RR: 1.51; 95% CI: 1.08–2.12; p = 0.02; I2 = 0%), and hypothyroidism (RR: 3.14; 95% CI: 1.10–8.95; p = 0.03; I2 = 81%) of any grade. Regarding adverse events of grade 3–4, there was no association of the addition of PD-1/PD-L1 inhibitors with an increased occurrence of any of the evaluated outcomes. ConclusionIn this systematic review and meta-analysis, the incorporation of PD-1/PD-L1 inhibitors to chemotherapy demonstrated an excellent safety profile and to be a promising prospect for reshaping the established treatment paradigms for patients with extensive-stage small cell lung cancer.

Extensive-stage small-cell lung cancer in patients receiving atezolizumab plus carboplatin–etoposide: stratification of outcome based on a composite score that combines gene expression profiling and immune characterization of microenvironment

PurposeSmall-cell lung cancer (SCLC) is an aggressive disease with a dismal prognosis. The addition of immune checkpoints inhibitors to standard platinum-based chemotherapy in first-line setting achieves a durable benefit only...

Efficacy and safety of sintilimab in combination with chemotherapy for recurrent extensive-stage small cell lung cancer: a real-world retrospective study.

Immune checkpoint inhibitors (ICIs) no longer are approved for second-line or later treatment of extensive-stage small cell lung cancer (ES-SCLC), and have not been studied in combination with chemotherapy. Exploring the efficacy and safety of second-line or later immunotherapy for ES-SCLC is an urgent clinical question that needs to be addressed, and combination therapies are an important research direction. This study intended to investigate the efficacy and safety of the sintilimab in combination with chemotherapy as a second-line and beyond treatment option for ES-SCLC. Medical records of patients who received treatment with sintilimab in combination with chemotherapy or chemotherapy alone as a second-line or beyond therapy were retrospectively analyzed. The study evaluated efficacy and safety. Indicators of efficacy included objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS). Safety indicators included adverse events (AEs). This cohort comprised of 46 patients: 24 in the sintilimab combination chemotherapy group and 22 in the chemotherapy group. Chemotherapy received by both groups was either albumin-bound paclitaxel or irinotecan. Compared with the chemotherapy group, the sintilimab combination chemotherapy group had higher ORR and DCR (ORR: 37.5% vs. 9.1%, P=0.04; DCR: 75.0% vs. 40.9%, P=0.04), and significantly prolonged PFS and OS [median PFS (mPFS): 5.07 vs. 2.45 months, P=0.006; median OS (mOS): 14.43 vs. 10.34 months, P=0.009]. Also, there was no significant increase in the incidence of AEs in the sintilimab combination chemotherapy group, which was well tolerated by patients. Sintilimab in combination with chemotherapy is superior to single-agent chemotherapeutic treatment as second-line or later therapy in ES-SCLC patients who have not received prior immunotherapy. These results need to be confirmed in future clinical trials.