IMpower133: Updated overall survival (OS) analysis of first-line (1L) atezolizumab (atezo) + carboplatin + etoposide in extensive-stage SCLC (ES-SCLC)

Reck, M.; Liu, S.V.; Mansfield, Aaron S.; Mok, Tony; Scherpereel, Arnaud; Reinmuth, Niels; Garassino, Marina Chiara; Carpeno, J. De Castro; Califano, Raffaele; Nishio, Makoto; Orlandi, F; Alexander, Jorge Arturo Alatorre; Leal, Ticiana; Cheng, Ying; Lee, J.-S.; Lam, S.; McCleland, Mark L.; Deng, Yu; Phan, See; Horn, Leora

doi:10.1093/annonc/mdz264

Cited by 58 publications

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“…The incidence of toxicity of any grade was similar between the two groups. Blood tumour mutation burden and PD-L1 did not show to be predictive biomarkers [20]. On March 18, 2019, the food and drug administration (FDA) approved atezolizumab in combination with carboplatin and etoposide, for the firstline treatment of adult patients with ES-SCLC, followed by the European medicines agency (EMA) on September 6, 2019 (I, A).…”

Section: Combined Chemotherapy and Immunotherapymentioning

confidence: 99%

SEOM clinical guidelines for the treatment of small-cell lung cancer (SCLC) (2019)

et al. 2020

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Small-cell lung cancer (SCLC) accounts for 15% of lung cancers. Only one-third of patients are diagnosed at limited stage. The median survival remains to be around 15-20 months without significative changes in the strategies of treatment for many years. In stage I and IIA, the standard treatment is the surgery followed by adjuvant therapy with platinum-etoposide. In stage IIB-IIIC, the recommended treatment is early concurrent chemotherapy with platinum-etoposide plus thoracic radiotherapy followed by prophylactic cranial irradiation in patients without progression. However, in the extensive stage, significant advances have been observed adding immunotherapy to platinum-etoposide chemotherapy to obtain a significant increase in overall survival, constituting the new recommended standard of care. In the second-line treatment, topotecan remains as the standard treatment. Reinduction with platinum-etoposide is the recommended regimen in patients with sensitive relapse (≥ 3 months) and new drugs such as lurbinectedin and immunotherapy are new treatment options. New biomarkers and new clinical trials designed according to the new classification of SCLC subtypes defined by distinct gene expression profiles are necessary.

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Section: Combined Chemotherapy and Immunotherapymentioning

confidence: 99%

SEOM clinical guidelines for the treatment of small-cell lung cancer (SCLC) (2019)

et al. 2020

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“…Clinically meaningful improvements in health‐related quality of life (HRQoL) that persisted beyond a year were also reported for the atezolizumab combination [49]. At a longer median follow‐up of 22.9 months, the improvement in median OS was maintained for the atezolizumab combination versus placebo (12.3 vs. 10.3 months; HR, 0.76; 95% CI, 0.60─0.95; descriptive p = .015) [50]. Rates of discontinuation due to adverse events (AEs) were higher in the atezolizumab arm, although rates of grade 3/4 TRAEs and treatment‐related death were comparable (Table 2).…”

Section: Resultsmentioning

confidence: 99%

“…Patient populations were comparable in terms of age, Eastern Cooperative Oncology Group (ECOG) performance status (PS), and extent of central nervous system (CNS) metastases for IMpower 133 and CASPIAN [37, 40], whereas patients in KEYNOTE‐604 had a slightly higher proportion of patients with PS 1 and CNS metastases [48]. Although ICI survival benefits emerged between 6 and 7 months with curves remaining separate at a median follow‐up of approximately 20 months in all trials [48, 50, 52], the survival benefit reached statistical significance for IMpower 133 and CASPIAN [50, 52] and was narrowly missed for KEYNOTE‐604 ( p = .016, OS superiority threshold p = .0128) [48]. ICI plus chemotherapy combinations improved HRQoL in IMpower 133 [49] and CASPIAN [51], although HRQoL data were not available for KEYNOTE‐604 [48].…”

Section: Discussionmentioning

confidence: 99%

“…ICI plus chemotherapy combinations improved HRQoL in IMpower 133 [49] and CASPIAN [51], although HRQoL data were not available for KEYNOTE‐604 [48]. Although caution should be exercised when considering cross‐trial comparisons, OS differences might be explained by a greater proportion of patients with poor prognosis enrolled in KEYNOTE‐604 as evidenced by the lower median OS for the control arm of this trial compared with IMpower 133 and CASPIAN (9.7 vs. 10.3 and 10.5 months, respectively) [48, 50, 52]. Another possibility could be that PD‐1 inhibitors are less effective at mediating immune responses compared with PD‐L1 inhibitors in SCLC, although this is unlikely given the improved survival demonstrated with the addition of nivolumab to chemotherapy in the phase II ECOG‐ACRIN 5161 study [55].…”

Section: Discussionmentioning

confidence: 99%

“…PD‐L1 inhibitors were combined with first‐line chemotherapy in IMpower 133 [37], CASPIAN [40], and KEYNOTE‐604 [48]. The addition of PD‐1/PD‐L1 inhibitors to platinum‐based chemotherapy generally resulted in comparable rates of grade 3/4 TRAEs for the combinations relative to controls (Table 2) [48, 50, 52]. However, rates of discontinuation due to AEs were higher for the ICI arm relative to chemotherapy in both IMpower 133 and KEYNOTE‐604 [48, 50] and were comparable in CASPIAN [52].…”

Section: Discussionmentioning

confidence: 99%

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Prolonging Survival: The Role of Immune Checkpoint Inhibitors in the Treatment of Extensive-Stage Small Cell Lung Cancer

et al. 2020

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Background Small cell lung cancer (SCLC) represents approximately 15% of lung cancers, and approximately 70% are diagnosed as extensive‐stage SCLC (ES‐SCLC). Although ES‐SCLC is highly responsive to chemotherapy, patients typically progress rapidly, and there is an urgent need for new therapies. Immune checkpoint inhibitors (ICIs) have recently been investigated in SCLC, and this review provides guidance on the use of these agents in ES‐SCLC based on phase III evidence. Methods Published and presented literature on phase III data addressing use of ICIs in ES‐SCLC was identified using the key search terms “small cell lung cancer” AND “checkpoint inhibitors” (OR respective aliases). Directed searches of eligible studies were periodically performed to ensure capture of the most recent data. Results Six phase III trials were identified, with four assessing the benefits of ICIs plus chemotherapy first‐line, one evaluating ICIs as first‐line therapy maintenance, and one assessing ICI monotherapy after progression on platinum‐based chemotherapy. The addition of ipilimumab or tremelimumab to first‐line treatment or as first‐line maintenance did not improve survival. Two out of three studies combining PD‐1/PD‐L1 inhibitors with first‐line platinum‐based chemotherapy demonstrated significant long‐lasting survival benefits and improved quality of life with no unexpected safety concerns. PD‐1/PD‐L1 inhibitors as first‐line maintenance or in later lines of therapy did not improve survival. Biomarker research is ongoing as well as research into the role of ICIs in combination with radiation therapy in limited‐stage SCLC. Conclusion The addition of atezolizumab or durvalumab to first‐line platinum‐based chemotherapy for ES‐SCLC prolongs survival and improves quality of life. Implications for Practice Platinum‐based chemotherapy has been standard of care for extensive‐stage small cell lung cancer (ES‐SCLC) for more than a decade. Six recent phase III trials investigating immune checkpoint inhibitors (ICIs) have clarified the role of these agents in this setting. Although ICIs were assessed first‐line, as first‐line maintenance, and in later lines of therapy, the additions of atezolizumab or durvalumab to first‐line platinum‐based chemotherapy were the only interventions that significantly improved overall survival and increased quality of life. These combinations should therefore be considered standard therapy for first‐line ES‐SCLC. Biomarker research and investigations into the role of ICIs for limited‐stage disease are ongoing.

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Small Cell Lung Cancer: Biology Advances

Hann

2021

Lung Cancer

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IMpower133: Updated overall survival (OS) analysis of first-line (1L) atezolizumab (atezo) + carboplatin + etoposide in extensive-stage SCLC (ES-SCLC)

Cited by 58 publications

References 0 publications

SEOM clinical guidelines for the treatment of small-cell lung cancer (SCLC) (2019)

SEOM clinical guidelines for the treatment of small-cell lung cancer (SCLC) (2019)

Prolonging Survival: The Role of Immune Checkpoint Inhibitors in the Treatment of Extensive-Stage Small Cell Lung Cancer

Small Cell Lung Cancer: Biology Advances

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