First-Line Treatment for Advanced SCLC: What Is Left Behind and Beyond Chemoimmunotherapy

Giunta, Emilio Francesco; Addeo, Alfredo; Rizzo, Annalisa; Banna, Giuseppe Luigi

doi:10.3389/fmed.2022.924853

Cited by 9 publications

(2 citation statements)

References 51 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In addition to biomarkers, there have been early investigations into identifying SCLC subtypes based on transcription factor expression [ 38 ], as well as varying immune signatures [ 39 ]. However, these models are not yet validated [ 40 ]. Overall, predictive biomarkers continue to be elusive, and further data are required to appropriately select patients who may derive a durable benefit with chemo-ICI above the expected benefits of chemotherapy in ES-SCLC.…”

Section: Discussionmentioning

confidence: 99%

Chemo-Immunotherapy in First Line Extensive Stage Small Cell Lung Cancer (ES-SCLC): A Systematic Review and Meta-Analysis

et al. 2022

View full text Add to dashboard Cite

Small cell lung cancer (SCLC) is an aggressive neuroendocrine carcinoma with early metastatic potential. The standard-of-care treatment has not changed in years. Recent studies report improved progression-free survival (PFS) and overall survival (OS) with combined ICI and chemotherapy in ES-SCLC. We conducted a systematic review and meta-analysis to assess the magnitude of survival benefits. We searched MEDLINE, EMBASE, and Cochrane between 1 January 2010 and 15 July 2022 and conference proceedings from 2018 to 2022, for randomised controlled trials, evaluating chemo-ICI compared with platinum-doublet chemotherapy in untreated ES-SCLC. Outcomes assessed were PFS, OS, objective response rate (ORR), duration of response (DoR), toxicity, and health-related quality of life (HRQoL). The search identified 8061 studies, with 8 (56 publications) included in the final analysis. PFS and OS were significantly improved for patients randomised to chemo-ICI (PFS hazard ratio (HR) 0.75, 95% confidence interval (CI) 0.70–0.80) and (OS HR 0.79, 95% CI 0.73–0.85). Subgroup analysis demonstrated a differential effect between PD-1/PD-L1 and CTLA-4 inhibitors. There was no difference in ORR and DoR. All-grade adverse events (RR 1.06, 95% CI 1.00–1.12) were similar. The addition of ICI to chemotherapy in untreated ES-SCLC results in a 22% risk reduction in death, and a 25% risk reduction in disease progression with a minimal increase in toxicity. These improvements are modest but represent progress beyond the standard of care.

show abstract

Section: Discussionmentioning

confidence: 99%

Chemo-Immunotherapy in First Line Extensive Stage Small Cell Lung Cancer (ES-SCLC): A Systematic Review and Meta-Analysis

et al. 2022

View full text Add to dashboard Cite

show abstract

“…An example is AK112, a bispecific antibody against PD-1 and VEGF, that is in a Phase 1b/2a clinical trial (NCT05116007) with carboplatin and etoposide. [54] e) Other chemoimmunotherapy combinations New chemoimmunotherapy combinations include 177Lu-DOTATATE, a somatostatin receptortargeted radionuclide therapy, since SCLC is a neuroendocrine tumor, which expresses somatostatin receptors [ 55 ]; BMS-986012, an anti-fucosyl-GM1 monoclonal antibody in a Phase 2 trial since fucosyl-GM1, a tumor-associated antigen, is highly expressed on SCLC cells but not on normal tissue; and LB-100, a small molecule inhibitor of protein phosphatase 2A (PP2A), which is overexpressed in SCLC. [56]…”

Section: D) Antiangiogenicsmentioning

confidence: 99%

A 2022 Update on Extensive Stage Small-Cell Lung Cancer (SCLC)

Oronsky¹,

Abrouk²,

Caroen³

et al. 2022

J. Cancer

View full text Add to dashboard Cite

For close to 40 years small-cell lung cancer (SCLC) was adrift, as listless, and as idle as a painted ship on a painted ocean, with nary a breeze to blow in the direction of clinical progress or change. The preferred decades-old first line regimen was etoposide-platinum, to which >50% of patients respond, followed by decades-old, tired topotecan in second line for platinum sensitive patients, full stop, because there were no approved therapeutic options (nor generally any compelling experimental ones) in third line or beyond. In 2012 SCLC was designated by the U.S. Congress as a "recalcitrant" tumor type and for good reason: because most patients relapse, after the generally favorable response in first line, respond poorly, if at all to subsequent therapies, and rarely survive beyond 1 year. A significant sea change occurred in 2018 with the approval of nivolumab followed by pembrolizumab and atezolizumab in 2019, durvalumab in 2020, accelerated approval for lurbinectedin in 2020 and trilaciclib in 2021 for myelosuppression. In 2021, the US indications for nivolumab and pembrolizumab were withdrawn. Suddenly, a tumor type, whose name was virtually synonymous with stalled progress and movement, and which was much less well studied and funded than its more prevalent cousin, non-small cell lung cancer (NSCLC), finds itself in the eye of the storm, that is, at the epicenter of an intense flurry and ferment of activity, not all of it positive. This review surveys approved drugs and select up-and-coming ones in development for extensive stage SCLC.

show abstract