Outcomes of first-line anti-PD-L1 blockades combined with brain radiotherapy for extensive-stage small-cell lung cancer with brain metastasis

Ma, Ji; Tian, Yaru; Hao, Shaoyu; Zheng, Lei; Hu, Weibo; Zhai, Xuechao; Meng, Dongfang; Zhu, Hui

doi:10.1007/s11060-022-04111-7

Cited by 6 publications

(4 citation statements)

References 30 publications

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“…Although ES‐SCLC has traditionally had a poor prognosis, recent phase three trials have confirmed improved outcomes with the addition of ICIs to chemotherapy 8,9,11,20 . However, only a few retrospective studies reported the survival outcomes in the real world, some without control groups, 21,22 some with insufficient case numbers, 23,24 and some including only PD‐L1 inhibitors 25–27 . Concerns about the inconsistency of anti‐PD‐1 agents and anti‐PD‐L1 agents suggested by the consequences of clinical trials are inconclusive 10,11 .…”

Section: Discussionmentioning

confidence: 99%

“… 8 , 9 , 11 , 20 However, only a few retrospective studies reported the survival outcomes in the real world, some without control groups, 21 , 22 some with insufficient case numbers, 23 , 24 and some including only PD‐L1 inhibitors. 25 , 26 , 27 Concerns about the inconsistency of anti‐PD‐1 agents and anti‐PD‐L1 agents suggested by the consequences of clinical trials are inconclusive. 10 , 11 The clinical benefits obtained from ICIs therapy in real‐world ES‐SCLC patients are still worth exploring.…”

Section: Discussionmentioning

confidence: 99%

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Clinical impact of first‐line PD‐1 or PD‐L1 inhibitors combined with chemotherapy in extensive‐stage small cell lung cancer patients: A real‐world multicenter propensity score‐matched study

et al. 2023

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Objectives: Our research aimed to evaluate the effectiveness of first-line immune checkpoint inhibitors (ICIs) with etoposide and platinum (EP) for extensive-stage small cell lung cancer (ES-SCLC) and identify prognostic factors, as real-world outcomes and the inconsistency of PD-1 and PD-L1 inhibitors are uncertain. Methods: We selected ES-SCLC patients in three centers and conducted a propensity score-matched analysis. The Kaplan-Meier method and Cox proportional hazards regression were conducted to compare the survival outcomes. We also performed univariate and multivariate Cox regression analyses to investigate predictors. Results: Among 236 patients included, 83 pairs of cases were matched. The EP plus ICIs cohort had a longer median overall survival (OS) (17.3 months) than the EP cohort (13.4 months) (hazard ratio [HR], 0.61 [0.45, 0.83]; p = 0.001). The median progression-free survival (PFS) was also longer in the EP plus ICIs cohort (8.3 months) than in the EP cohort (5.9 months) (HR, 0.44 [0.32, 0.60]; p < 0.001). The EP plus ICIs group had a higher objective response rate (ORR) (EP: 62.3%, EP + ICIs: 84.3%, p < 0.001). Multivariate analysis presented that liver metastases (HR, 2.08; p = 0.018) and lymphocyte-monocyte ratio (LMR) (HR, 0.54; p = 0.049) were independent prognostic factors for OS, and performance status (PS) (HR, 2.11; p = 0.015), liver metastases (HR, 2.64; p = 0.002), and neutrophillymphocyte ratio (NLR) (HR, 0.45; p = 0.028) were for PFS in patients with chemoimmunotherapy. Conclusion: Our real-world data demonstrated that ICIs with chemotherapy as the first-line setting for ES-SCLC are effective and safe. PS, liver metastases, and inflammatory markers could serve as valuable risk factors.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Clinical impact of first‐line PD‐1 or PD‐L1 inhibitors combined with chemotherapy in extensive‐stage small cell lung cancer patients: A real‐world multicenter propensity score‐matched study

et al. 2023

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“…Second, many patients did receive radiotherapy concurrently with atezolizumab (19.5%), including brain radiotherapy in 5% of patients. Interestingly, baseline brain metastases did not significantly impact outcomes in our cohort, which may be related to a selection of asymptomatic, stable cases, as well as to the delivery of radiotherapy, that was previously reported to be safe [19]. Third, while radiotherapy may have been administered upfront, IFCT-1905 CLINA-TEZO shows that a high proportion − 24%-of patients were treated with atezolizumab beyond progression, for a median duration of 1.9 (95% CI [1.4-2.3]) months, possibly in the setting of focal treatment of oligoprogressive disease, found in 42 (8%) patients who continued atezolizumab post-progression, and 22 (4%) patients who discontinued atezolizumab, a strategy adopted in clinical practice in non-small cell lung cancer (NSCLC), treated with immunotherapy or targeted agents [20,21].…”

Section: Discussionmentioning

confidence: 56%

Long-term effectiveness and treatment sequences in patients with extensive stage small cell lung cancer receiving atezolizumab plus chemotherapy: Results of the IFCT-1905 CLINATEZO real-world study.

Falchero

Guisier

Darrason

et al. 2023

JCO

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8583 Background: Small cell lung cancer (SCLC) is a highly aggressive type of lung cancer with a tendency towards early recurrence and limited survival. Standard-of-care in 1st-line treatment is platinum-etoposide chemotherapy plus anti-PD-L1 immune checkpoint inhibitor atezolizumab or durvalumab, based on landmark, randomized, phase 3 clinical trials. Methods: IFCT 1905-CLINATEZO is a nationwide, non-interventional, retrospective chart review study of patients (pts) with extensive-stage SCLC who received atezolizumab + chemotherapy as part of the French early access program between May 2019 and January 2020 (1402 pts). Inclusions were exhaustive per participating centers (65/307). Data collection run from February to November 2021. Key objectives were to assess effectiveness and safety of atezolizumab + chemotherapy and analyze subsequent treatment sequences. Results: The population analyzed included 518 out of the 1402 pts. There were 66% male and mean age was 65.7 years (range: 36.7-88.0); 89% had a performance status (PS) 0/1 and 27% brain metastases. Almost all the pts (96%) were smokers, with a median number of pack-years of 40. Fifty-five pts (10.6%) received at least 1 previous treatment. Median number of atezolizumab injections was 7 (range: [1-48] ) for a median duration of 4.9 months (95% CI 4.5-5.1). Twenty-seven pts (5%) were under ongoing treatment at date of last news. Atezolizumab was continued beyond disease progression in 122 pts (24%) for a median duration of 1.9 months (95% CI 1.4-2.3). Best objective response was complete and partial response in 19 (3.9%) and 378 pts (77.1%) respectively; stable disease was observed in 50 pts (10.2%). After a median follow-up of 30.8 months (95% CI: [29.9-31.5]), median overall survival (OS), 12- and 24-months OS rates were 11.3 months (95% CI: [10.1-12.4]), 46.7% (95% CI 42.3-50.9) and 21.2% (95% CI 17.7-24.8) respectively. Median real world-progression free survival (based on date of the first source evidence for progression referenced by the treating physician), 6- and 12-months rates were 5.2 months (95% CI 5.0-5.4), 37.5% (95% CI 33.3-41.7) and 15.2% (95% CI 12.2-18.6) respectively. For the pts with PS 0/1, median OS was 12.2 months (95% CI 11.0-13.5). For the 55 pts with previous treatment, median OS was 14.9 months (95% CI 10.1-21.5). A total of 326 (66.4%) pts received subsequent treatment. Conclusions: IFCT 1905-CLINATEZO study shows the reproducibility, in a real-life setting, of the key survival outcomes of IMpower-133, that may be attributed to the selection of pts fit for this regimen, the adoption of pragmatic approaches for the management of pts receiving atezolizumab, that includes concurrent radiotherapy and treatment beyond progression, and the high proportion of pts treated with 2nd-line therapies, mostly based on chemotherapy.

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“…Although immunotherapy combined with chemotherapy (ICT) plays a signi cant role in ES-SCLC, data related to the combined e cacy and safety of RT is insu cient, and the results are controversial. A single-center retrospective study analyzing the safety and e cacy of rst-line ICT combined with CTRT for ES-SCLC showed estimated OS rates of 97.1%, 80.2%, and 53.3% at 6 months, 1 year, and 2 years, respectively, with controlled safety However, another study indicated that the combination of rst-line anti-PD-L1 blockade with BRT did not confer a signi cant survival bene t in patients with ES-SCLC with BMs [44]. These results suggest that the addition of RT to ICT may yield different outcomes.…”

Section: Earlier Initiation Of Rit In Es-sclc Leads To Improved Survi...mentioning

confidence: 99%

Immune activation effects at different irradiated sites and optimal timing of radioimmunotherapy in patients with extensive-stage small cell lung cancer: a real-world analysis

Wang

Chen

et al. 2023

Preprint

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Background In view of the limited data on radiotherapy (RT) combined with immunotherapy in patients with extensive-stage small cell lung cancer (ES-SCLC), this study aimed to identify the immune activation effect on different sites and the survival outcomes of radioimmunotherapy at different treatment stages. Methods Forty-five patients diagnosed with ES-SCLC were included in this retrospective analysis. We collected the overall survival (OS) of the patients,, recorded the blood cell counts before, during, and after RT, and derived blood index ratios such as the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and systemic immune-inflammation index (SII). The datasets were analyzed using the Spearman rank correlation test, Kruskal-Wallis rank sum test, logistic regression, and survival analysis. Results Among the selected blood indices, the delta-NLR/PLR/Sll correlated with different irradiated organs, and the mean ranks of these three indices were the lowest in the brain-irradiated group during immunotherapy. Additionally, adjunct first-line immunotherapy with RT demonstrated a significant improvement compared to second- or third-line therapy and subsequent therapies. Conclusion Our findings suggest that compared to other organs, the strongest immune activation effect occurs with brain RT, and ES-SCLC patients who received radioimmunotherapy (RIT) earlier achieved higher OS rates.

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Outcomes of first-line anti-PD-L1 blockades combined with brain radiotherapy for extensive-stage small-cell lung cancer with brain metastasis

Cited by 6 publications

References 30 publications

Clinical impact of first‐line PD‐1 or PD‐L1 inhibitors combined with chemotherapy in extensive‐stage small cell lung cancer patients: A real‐world multicenter propensity score‐matched study

Clinical impact of first‐line PD‐1 or PD‐L1 inhibitors combined with chemotherapy in extensive‐stage small cell lung cancer patients: A real‐world multicenter propensity score‐matched study

Long-term effectiveness and treatment sequences in patients with extensive stage small cell lung cancer receiving atezolizumab plus chemotherapy: Results of the IFCT-1905 CLINATEZO real-world study.

Immune activation effects at different irradiated sites and optimal timing of radioimmunotherapy in patients with extensive-stage small cell lung cancer: a real-world analysis

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