Extensive Small Cell Lung Cancer Research Articles

2008P Brazilian real-world data of immunotherapy (IO) in extensive disease small cell lung cancer (ES-SCLC)

2008P Brazilian real-world data of immunotherapy (IO) in extensive disease small cell lung cancer (ES-SCLC)

LBA93 EXTENTORCH: A randomized, phase III trial of toripalimab versus placebo, in combination with chemotherapy as a first-line therapy for patients with extensive stage small cell lung cancer (ES-SCLC)

LBA93 EXTENTORCH: A randomized, phase III trial of toripalimab versus placebo, in combination with chemotherapy as a first-line therapy for patients with extensive stage small cell lung cancer (ES-SCLC)

2009P CNS efficacy of immune checkpoint inhibitors when combined to stereotactic radiosurgery in extensive stage small cell lung cancer

2009P CNS efficacy of immune checkpoint inhibitors when combined to stereotactic radiosurgery in extensive stage small cell lung cancer

PD-L1 Inhibitors Combined with Thoracic Radiotherapy in First-Line Treatment of Extensive Stage Small Cell Lung Cancer: A Propensity Score-Matched, Real-World Study

The CREST study showed that the addition of thoracic radiotherapy (TRT) could improve the survival of extensive stage small cell lung cancer (ES-SCLC), but whether TRT can bring survival benefit in the era of immunotherapy is controversial. This study aims to explore the efficacy and safety of adding TRT to the combination of PD-L1 inhibitors and chemotherapy. Thepatients who received PD-L1 inhibitors combined with platinum-based chemotherapy as the first-line treatment of ES-SCLC from January 2019 to December 2021 were retrospectively collected. According to whether they received TRT, they were divided into two groups, and the follow-up analysis was performed. Propensity score matching (PSM) in with a 1:1 ratio was performed to balance the baseline characteristics of the two cohorts. The endpoints were progression-free survival (PFS) and OS. A total of 211 patients with ES-SCLC were enrolled, of whom 70 (33.2%) patients received standard therapy plus TRT as first-line treatment, and 141 (66.8%) patients in the control group received PD-L1 inhibitors plus chemotherapy. After PSM, a total of 65 pairs of patients were enrolled in the analysis. There were no significant differences in baseline characteristics between the two groups of patients who received TRT and those who did not. In all patients, the median PFS (mPFS) in the TRT group and the non-TRT groupwere 9.5 months and 7.2 months, respectively, with HR = 0.60 (95% CI 0.41-0.87, p = 0.007). The median OS (mOS) in the TRT group was also significantly longer than that in the non-TRT group (24.1 months vs. 18.5 months, HR = 0.53, 95% CI 0.32-0.85, p = 0.009). Multivariable analysis showed that baseline liver metastasis and bone metastasis were independent prognostic factors for OS. In terms of safety, immunotherapy combined with thoracic radiotherapy increased the incidence of treatment-related pneumonia (p<0.001), most of which were grade 1-2. This real-world study shows that adding TRT to durvalumab or atezolizumab plus chemotherapy significantly improves survival in ES-SCLC. It leads to more treatment-related pneumonia, but most of them can be relieved after symptomatic treatment. This treatment model deserves to be explored in prospective clinical trials.

30 Gy vs. 45 Gy Consolidative Thoracic Radiation (cTRT) for Extensive Stage Small Cell Lung Cancer (ES-SCLC): A Multicenter, Randomized, Phase 3 Trial

Consolidative thoracic radiotherapy (cTRT) showed potential benefit to extensive stage small cell lung cancer (ES-SCLC). However, the optimum dose of cTRT is unknown. The purpose of this randomized trial was to compare the effect of 45 Gy in 15 fractions with 30 Gy in 10 fractions cTRT in ES-SCLC. This phase III, randomized trial was conducted in 12 public hospitals in China. Eligible patients with pathologically confirmed ES-SCLC who responded to 4-6 cycles of etoposide plus cisplatin (EP) or carboplatin (EC) chemotherapy were randomized 1:1 to receive either 30 Gy in 10 fractions or 45 Gy in 15 fractions cTRT. The primary outcome was 2-year overall survival (OS). Secondary outcomes included 2-year progression-free survival (PFS), 2-year local control (LC) and radiation treatment related toxicity. The primary objective was to detect an OS improvement in 45 Gy cTRT group at 2 years from 13% to 26% assuming a two-sided a = 0.05 and power of 85%, with a planned sample size of 186 patients. This trial was registered with Clinical Trials.gov, number NCT02675088. Between January 15, 2016, and September 20, 2022, 90 patients were randomly assigned either 30 Gy in 10 fractions (n = 50) or 45 Gy in 15 fractions (n = 40) cTRT group. Recruitment to the trial closed early due to slow accrual since first-line chemoimmunotherapy has become the new standard of care for ES-SCLC. The median age of patients was 58 years, 87.8% were male, 76.7% had a smoking history, 95.6% received IMRT, and 58.9% received prophylactic cranial irradiation. At a median follow-up of 39.9 months (IQR 27.2-59.2), there was no significant difference in the 2-year OS between the 45 Gy group and the 30 Gy group, at 43.4% (95% CI 29.3%-64.3%) and 40.0% (95% CI 27.9%-59.1%), respectively (log-rank p = 0.62; HR 1.13 [95% CI 0.69-1.84]). The 2-year PFS was 12.1% (95% CI 4.3%-33.8%) in the 45 Gy group and 9.0% (95% CI 3.2%-25.2%) in the 30 Gy group (log-rank p = 0.25, HR 0.76(95% CI [0.478-1.22]). There were also no significant differences in locoregional recurrence free survival (log-rank p = 0.75; HR 0.888 [95% CI 0.423-1.863]) and distant metastasis free survival (log-rank p = 0.95; HR 1.015 [95% CI 0.624-1.651]) between two groups. No grade 5 toxicity was observed in both groups. Patients treated with higher cTRT dose presented with increased incidence of grade 3+ radiation pneumonitis (10% vs 2%) and hematological toxicity (20% vs 12.5%). This randomized trial did not find a higher probability of survival improvement in patients with ES-SCLC receiving cTRT of 45 Gy in 15 fractions compared with 30 Gy in 10 fractions. In contrast, there was an increase in toxicity, especially radiation pneumonitis. Additional randomized studies investigating the role of cTRT in ES-SCLC after a response to chemoimmunotherapy are warranted.

Survival Outcomes of Extensive Stage Small Cell Lung Cancer Patients Treated with Consolidative Thoracic Radiotherapy at a Tertiary Cancer Center

Most small cell lung cancer cases present as Stage IV (M1) or extensive stage (ES-SCLC), which are defined as tumor extending outside the hemithorax without a tolerable radiation portal. The CREST trial demonstrated improved local control with a modest overall survival (OS) benefit at the 2-year secondary endpoint of 14% survival with consolidative thoracic radiotherapy (CTRT) compared to 3% without CTRT. Low toxicity rates were also observed. This study reports our institutional ES-SCLC experience for patients treated with CTRT. A retrospective review was conducted on ES-SCLC patients treated with CTRT at our institution between 2014 and 2019. CTRT was defined as ≥30 Gy of thoracic radiotherapy. OS and tolerability of treatment were assessed in this population. Chemotherapy details were also captured. OS rate was determined using the Kaplan-Meier method and the time from start of CTRT to last date of follow-up or death. CTRT tolerability was determined using incidence and grade of esophagitis and radiation pneumonitis as per CTCAE v5. We identified 100 ES-SCLC patients treated with any thoracic RT at our institute, of which 45 received thoracic RT for palliative intent or with <30 Gy. The remaining 55 patients received ≥30 Gy CTRT and were included for analysis. The median age was 65.1 years (range 46.6-86.9) and 36 (65%) were male. The median follow-up for this sample was 0.8 (range 0.03-4.2) years. Median chemotherapy cycles were 6 (range 1-6), most receiving ≥4 cycles (87%) and completing chemotherapy prior to CTRT initiation (91%) with a minority concurrently receiving chemotherapy and CTRT (9%). Platinum chemotherapy was the most common (96%) with 2 patients receiving etoposide alone (4%). The most common CTRT regimens were 30 Gy in 10 fractions (80%) followed by 40 Gy in 15 fractions (9%) and 45 Gy in 30 twice-daily fractions (7%). Most patients (67%) were treated with IMRT/VMAT technique, while the remaining (33%) patients were treated with 3DCRT. The median survival time was 1.3 years with 1- and 2-year OS of 57.2% (CI 44.0 - 74.3%) and 26.1% (CI 12.9 - 52.7%), respectively. CTRT was well tolerated with no grade 4+ toxicities. The most common toxicity was esophagitis with 21 patients (39%), of which 15 were G1 (28%) and 6 were G2 (11%). Radiation pneumonitis was present in 5 patients (9.2%) with 1 G1 (2%), 3 G2 (6%), and 1 G3 (2%) cases. Consolidative TRT for ES-SCLC in this institutional series was at least as good as the reported CREST outcome with modest acute toxicities in this cohort. Disease burden at diagnosis, chemotherapy response, patterns of failure, and subsequent therapies will be further investigated.

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

BackgroundSmall cell lung cancer (SCLC) has a tendency towards recurrence and limited survival. Standard-of-care in 1st-line is platinum-etoposide chemotherapy plus atezolizumab or durvalumab,based on landmarkclinical trials. MethodsIFCT-1905 CLINATEZO is a nationwide, non-interventional, retrospectivestudy of patients with extensive-SCLC receivingatezolizumab plus chemotherapy as part of French Early Access Program. Objectives were to analyse effectiveness,safetyand subsequent treatments. ResultsThe population analyzed included 518 patients who received atezolizumabin 65 participating centers. There were 66.2% male,mean age was 65.7 years; 89.1% had a performance status (PS) 0/1 and 26.6% brain metastases. Almost all(95.9%) were smokers. Fifty-five (10.6%) received at least 1 previous treatment. Median number of atezolizumab injections was 7.0 (range [1.0–48.0]) for a median duration of 4.9 months (95% CI 4.5–5.1). Atezolizumab was continued beyond progression in 122 patients (23.6%) for a median duration of 1.9 months (95% CI: [1.4–2.3]). Best objective response was complete and partialin 19 (3.9%) and 378 (77.1%)patients. Stable diseasewas observed in 50 patients (10.2%). Median follow-up was30.8 months (95% CI: [29.9–31.5]). Median overall survival (OS), 12-, 24-month 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]). Median real-world progression-free survival, 6-, 12-month 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]). For patients with PS 0/1, median OS was 12.2 months (95% CI [11.0–13.5]). For patients with previous treatment, median OS was 14.9 months (95% CI [10.1–21.5]). Three-hundred-and-twenty-six patients(66.4%) received subsequent treatment and27 (5.2%) were still underatezolizumabat date of last news. ConclusionsIFCT-1905 CLINATEZO shows reproductibility, in real-life,ofIMpower-133survival outcomes, possibly attributed to selection of patients fit for this regimen, adoption of pragmatic approaches,including concurrent radiotherapy and treatment beyond progression.

Impact of liver metastases status on survival outcomes of first-line immunotherapy in extensive stage small cell lung cancer: a systematic review and meta-analysis.

This study aims to assess the impact of liver metastases status on survival outcomes of first-line immunotherapy in extensive stage small cell lung cancer (ES-SCLC) patients. Comprehensive searches were conducted in the Cochrane Library databases, Embase, PubMed, and abstracts from WCLC, ESMO, and ASCO from inception to December 2022. Randomized controlled trials reporting progression-free survival (PFS) and/or overall survival (OS) of first-line immunotherapy in ES-SCLC patients were included. Six trials involving 3501 patients were analyzed, comprising 1350 patients with liver metastases and 2151 without. The quality of the included trials was consistently high. Pooled results revealed that immunotherapy plus chemotherapy did not significantly improve PFS (hazard ratio [HR] = 0.82, 95% confidence interval [CI]: 0.68-1.00, P = 0.05) and OS (HR = 0.89, 95% CI: 0.79-1.00, P = 0.05) in ES-SCLC patients with liver metastases compared to chemotherapy alone. However, immunotherapy plus chemotherapy improved PFS (HR = 0.66, 95% CI: 0.57-0.77, P < 0.01) and OS (HR = 0.74, 95% CI: 0.67-0.82, P < 0.01) in ES-SCLC patients without liver metastases compared to chemotherapy alone. First-line immunotherapy plus chemotherapy significantly improved PFS and OS in ES-SCLC patients without liver metastases compared to chemotherapy alone. However, patients with liver metastases did not experience comparable benefits.

Real-World Outcomes With Lurbinectedin in Second-Line Setting and Beyond for Extensive Stage Small Cell Lung Cancer

BackgroundLurbinectedin has emerged as a potential treatment option for relapsed small cell lung cancer (SCLC). While clinical trials have demonstrated its efficacy and safety, real-world data are limited. This study aimed to evaluate the safety and efficacy of lurbinectedin in a real-world setting, focusing on its use as a second-line agent and beyond in SCLC patients. MethodsA retrospective analysis was conducted on 90 patients who received lurbinectedin between June 2020 and June 2022 within the Mayo Clinic Health System. Of these, 50 patients received lurbinectedin as a second-line agent, and 14 patients received it as a third-line or later agent. The primary outcomes assessed were overall survival (OS), progression-free survival (PFS), and treatment-related adverse events. ResultsLurbinectedin was generally well tolerated in this real-world cohort, with a median OS of 5.1 months in the second-line cohort and 5.6 months in the third-line or later cohort. Median PFS was 2.1 months in the second-line cohort and 3.4 months in the third-line or later cohort. Adverse events were manageable, with the most common being neutropenia, anemia, fatigue, and febrile neutropenia. No treatment-related deaths or grade 5 toxicities were reported. ConclusionThis real-world study provides valuable insights into the safety and efficacy of lurbinectedin in relapsed SCLC. Lurbinectedin demonstrated modest efficacy and a comparable safety profile to that observed in clinical trials. However, outcomes for relapsed SCLC remain suboptimal, particularly for patients with a shorter chemotherapy-free interval and central nervous system metastases.

215 Survival Outcomes of Extensive Stage Small Cell Lung Cancer Patients Treated with Consolidative Thoracic Radiotherapy at a Tertiary Cancer Centre

215 Survival Outcomes of Extensive Stage Small Cell Lung Cancer Patients Treated with Consolidative Thoracic Radiotherapy at a Tertiary Cancer Centre

Efficacy and safety of thoracic radiotherapy for extensive stage small cell lung cancer after immunotherapy in real world.

The immunotherapy combined chemotherapy has been the standard treatment strategy for extensive-stage small lung cancer (ES-SCLC). The CREST trial reported consolidative thoracic radiotherapy (cTRT) improved overall survival (OS) for ES-SCLC with intrathoracic residual after chemotherapy. In this study, patients with ES-SCLC who received immunotherapy were assigned to receive either TRT or no TRT. TRT significantly improved progression-free survival (PFS), local recurrence-free survival (LRFS) and OS with well tolerated toxicity. Further sub-cohort analysis, TRT significantly improved LRFS in patients with oligo-metastasis and without liver metastasis.

Consolidative thoracic radiotherapy for extensive disease small cell lung cancer

Consolidative thoracic radiotherapy for extensive disease small cell lung cancer

Efficacy and safety of fluzoparib combined with anlotinib in extensive stage small cell lung cancer after first-line platinum-based chemotherapy: a multi-center, single-arm prospective phase II clinical study (STAMP study)

BackgroundSmall-cell lung cancer (SCLC) is a highly aggressive and lethal malignancy that accounts for 10–15% of lung cancers, and it is generally divided into limited and extensive stage. The standard of care for patients with newly diagnosed extensive-stage SCLC (ES-SCLC) is still platinum-based chemotherapy and as maintenance therapy scheme. Although most parts of patients experience a significant tumor response to first-line therapy, the disease recurs invariably. Anlotinib hydrochloride, a novel oral multitarget tyrosine kinase inhibitor, has significant inhibitory activity against angiogenesis-related kinases, such as VEGFR, FGFR, PDGFR, and c-Kit kinase associated with tumor cell proliferation. Fluzoparib is a type of inhibitor of poly ADP ribose polymerase (PARP, including PARPl, PARP2 and PARP3). Previous studies have shown that Fluzoparib has a strong inhibitory effect on PARP1 activity at the molecular and cellular levels.MethodsThis is a multi-center, prospective, single-arm phase II clinical study. A total of 50 ES-SCLC patients who experienced disease progression after first-line standard platinum-based chemotherapy with/without immune checkpoint inhibitors scheme, or within 6 months after the completion of treatment will be recruited. Those who had prior treatment with any PARP inhibitor or antiangiogenic agent includes anlotinib, bevacizumab, sorafenib, and thalidomide are excluded. Eligible patients will receive oral anlotinib 8 mg once daily and oral fluzoparib 150 mg twice daily until disease progression or intolerable toxicity. The primary endpoint is objective response rate (ORR).DiscussionThe addition of fluzoparib to anlotinib is expected to increase the clinical benefit in ES-SCLC patients after platinum-based chemotherapy.Trial registrationThis study protocol was prospectively registered on June 17, 2021. ClinicalTrials.gov Identifier: NCT04933175.

Real-world outcomes of PD-L1 inhibitors combined with thoracic radiotherapy in the first-line treatment of extensive stage small cell lung cancer

BackgroundThe CREST study showed that the addition of thoracic radiotherapy (TRT) could improve the survival rate in patients with extensive stage small cell lung cancer (ES-SCLC), but whether TRT can bring survival benefit in the era of immunotherapy remains controversial. This study aimed to explore the efficacy and safety of adding TRT to the combination of PD-L1 inhibitors and chemotherapy.MethodsThe patients who received durvalumab or atezolizumab combined with chemotherapy as the first-line treatment of ES-SCLC from January 2019 to December 2021 were enrolled. They were divided into two groups, based on whether they received TRT or not. Propensity score matching (PSM) with a 1:1 ratio was performed. The primary endpoints were progression-free survival (PFS), overall survival (OS) and safety.ResultsA total of 211 patients with ES-SCLC were enrolled, of whom 70 (33.2%) patients received standard therapy plus TRT as first-line treatment, and 141 (66.8%) patients in the control group received PD-L1 inhibitors plus chemotherapy. After PSM, a total of 57 pairs of patients were enrolled in the analysis. In all patients, the median PFS (mPFS) in the TRT and non-TRT group was 9.5 and 7.2 months, respectively, with HR = 0.59 (95%CI 0.39–0.88, p = 0.009). The median OS (mOS) in the TRT group was also significantly longer than that in the non-TRT group (24.1 months vs. 18.5 months, HR = 0.53, 95%CI 0.31–0.89, p = 0.016). Multivariable analysis showed that baseline liver metastasis and the number of metastases ≥ 3 were independent prognostic factors for OS. Addition of TRT increased the incidence of treatment-related pneumonia (p = 0.018), most of which were grade 1–2.ConclusionsAddition of TRT to durvalumab or atezolizumab plus chemotherapy significantly improves survival in ES-SCLC. Although it may leads to increased incidence of treatment-related pneumonia, a majority of the cases can be relieved after symptomatic treatment.

Relationship between immune-related adverse events and treatment effectiveness in extensive disease small cell lung cancer.

This study aimed to assess the relationship between immune response adverse events (irAEs) and treatment efficacy in patients with extensive disease small cell lung cancer (ED-SCLC). We retrospectively evaluated the clinical effects in 40 ED-SCLC patients who had received immune-checkpoint inhibitors (ICIs), platinum agents, and etoposide between September 2019 and September 2021. We identified and compared patients belonging to two groups: irAE and non-irAE. Fifteen patients experienced irAEs, and 25 did not. The median progression-free survival in patients with irAE was longer than that in patients without irAE (12.6 months [95% CI: 6.3-19.3 months] vs. 7.2 months [95% CI: 5.8-7.9 months], p = 0.0108). However, the median overall survival (OS) was similar between irAE and non-irAE groups (27.6 months [95% CI: 15.4-NA] vs. 24.9 months [95% CI: 13.7-NA], p = 0.268). Seven (46.7%) in the irAE group and 20 (80%) in the non-irAE group received sequential therapy. The median OS was prolonged in patients who received first- and second-line therapy than in those who received first-line therapy alone (27.6 months [95% CI: 19.2-NA] vs. 6.6 months [95% CI: 0.3-NA], p = 0.053). Grade ≧ 3 irAEs occurred in five (12.5%) patients. Among them, grade 5 irAEs were observed in two patients, including exacerbation of polymyositis and pulmonary arterial embolism. In this study, the development of irAEs did not affect OS in patients with ED-SCLC who received platinum-based agents, etoposide, or ICI therapy. We determined that managing irAEs and administering first- and second-line therapies could contribute to prolonged OS.

Outcomes and Prognostic Factors of Extensive Stage Small Cell Lung Cancer: A Retrospective Study

Introduction Small cell lung cancer (SCLC) represents about 15% of all lung cancers. Extensive stage (ES) SCLC represents around 60% of diagnosed SCLC cancers. The median survival in untreated ES SCLC is 2 to 4 months and that of treated cases is 8 to 13 months. Aim and Objectives This retrospective analysis aims to find out the clinical outcome of patients with ES SCLC and the prognostic factors affecting their survival. Methods Details of patients registered in the department of radiation oncology from January 1, 2010 to September 30, 2019 were retrieved from the hospital records. This includes the demographic characteristics, treatment received, toxicity, and follow-up details. Results Two-hundred eighty-three patients were included. Median age of presentation was 62 years. Around 97.5% of patients were men. Smokers constitute 94% of all cases. About 86.9% (246 patients) of cases were not alive at the end of the study period. The median estimated overall survival (OS) was 7 months ± 0.47 (95% confidence interval [CI]: 6.026–7.974) and progression-free survival (PFS) was 5 months ± 0.535 (95% CI: 3.952–6.048). Multivariate analysis showed that Eastern Cooperative Oncology Group performance status (ECOG PS), hyponatremia, number of chemotherapy cycles, consolidative radiotherapy (RT) and prophylactic cranial irradiation (PCI) were found to have prognostic effect on OS. Smoking, ECOG PS, number of chemotherapy cycles, consolidative RT, and PCI were found to have prognostic effects on PFS. Conclusion There is a difference in OS and PFS patterns of ES SCLC patients among various Indian studies even though the available data is scarce. Our study shows that the OS and PFS of our study population are comparable to other South Indian studies available. PS, serum sodium level, number of chemotherapy cycles, consolidative RT, and PCI were found to be independent prognostic factors for survival of ES SCLC. The identification of these factors will help physicians to tailor treatment.

Role of consolidative thoracic and prophylactic cranial radiation in extensive stage small cell lung cancer in chemo-immunotherapy era.

8595 Background: The role of consolidative thoracic and prophylactic brain radiation in extensive stage small cell lung cancer patients is controversial. We investigated the factors associated with the use of any radiation therapy (RT) and whether Radiation has a benefit to overall survival (OS) in the total patient group and whether this benefit is the same if Chemotherapy (CT) only is used, or chemo-immunotherapy (CT-IO) is used. Methods: The NCDB database was queried from years 2017-2019. Patients receiving systemic therapy- STX (CT or CT-IO) had to have at least 6 months of follow-up and have no brain metastases at diagnosis. All RT patients had to receive upfront systemic therapy, were treated 2 to 6 months from diagnosis, and if treated to the brain received 25Gy in 10 fractions only. Multi-variate analyses (MVA) were used to determine factors associated with OS and selection for any radiation. Propensity matching for factors affecting OS were used to generate Kaplan-Meier OS curves. Log-rank tests were used to determine differences in Kaplan Meier survival curves for the effects of RT on OS. Results: The total number of patients receiving RT or systemic therapy alone as well as their median follow-ups(months(mn) were (981, 33.02mn) and (8909, 30.59mn). The median time to the start of STX and RT were 22days and 135 days respectively. MVA noted that RT had a greater effect on OS (Thoracic, Brain, Both – HRs = 0.78, 0.75, and 0.68) than other interventions including IO (HR 0.87) and palliative care without RT (HR 1.07). Selection for radiation depended significantly upon factors affecting OS(HR) including liver metastases (0.59), females (1.21), age/10yr(0.78) and Charlson co-morbidity index of &gt; 3(0.66), but did not depend upon insurance status, race, or county income/high school graduation rates. Propensity score matched OS curves noted the same effects of RT on OS whether CT or CT-IO was given. The lowest HRs were noted when both thoracic and brain RT were given (see table). Conclusions: The patient with extensive stage small cell lung cancer who reach candidacy and receive RT may have a significant improvement in OS compared to the patients treated only with CT or CT-IO. Combined thoracic and prophylactic brain RT seems to be better than either one alone. The impact of radiation whether given to one or two sites may be more beneficial than immunotherapy added to chemotherapy. [Table: see text]

Molecular predictors and immunomodulatory role of dual checkpoint inhibitor blockade using ipilimumab/nivolumab in patients with extensive stage small cell lung cancer.

8597 Background: Small cell lung cancer (SCLC) is an aggressive neuroendocrine carcinoma with poor prognosis. In extensive stage patients, frontline treatment with chemoimmunotherapy shows modest clinical benefit. However, the biological impact of immunotherapy in SCLC is poorly understood with no clear predictive biomarkers to guide patient selection in this setting. Methods: We collected paired baseline (pre-treatment), on-treatment (week 4), and progression biopsies from patients with relapsed advanced-stage SCLC treated with combination nivolumab (nivo) and ipilimumab (ipi) in a single-arm, phase 2 clinical trial (NCT03670056). Nivo 1 mg/kg and ipi 3 mg/kg were administered every 3 weeks for 4 cycles, followed by nivo maintenance until progressive disease (PD) by RECIST 1.1 or treatment-limiting toxicity. Paired pre/on-treatment samples were available from 16/22 patients, as well as 3 biopsies at progression. The tumor samples were studied using whole exome DNA sequencing (including germline DNA) and RNA-sequencing coupled to Ocean Genomics TxomeAI data analysis pipeline. Results: 6/11 evaluable patients had PD; 5 patients showed clinical activity of treatment (3 with stable disease, 2 with partial response). The frequency of deleterious mutations in TP53 and RB1 was 91% and 64%, respectively. Mutations in HLA-A were more common in baseline samples from patients with PD than those with clinical activity. New TP53 and PLEC mutations were found 4 of 6 patients with PD in week 4 samples vs baseline. The baseline tumor mutational burden was not associated with treatment sensitivity and prominently increased in week 4 biopsies of PD patients. All four molecular SCLC transcriptomic subtypes based on the expression of ASCL1, NEUROD1, and POU2F3 were present in the trial with SCLC-A being the most common (9/16 cases). All patients with clinical activity to ipi/nivo were of SCLC-A subtype. 2/16 of cases showed a different molecular subtype after 4 weeks of treatment: one case with SCLC-N switched to SCLC-A and another case converted from SCLC-A to SCLC-N. Comparison of baseline and on-treatment samples showed upregulation of transcripts associated with T-cell activation and PD-1 signaling. In the 3 biopsies at progression, transcriptomic changes included reduction of neutrophil degranulation, type 1/2 interferon and signatures, as well as down-regulation of β-2 microglobulin, while cell cycle and mitotic prophase pathways were overexpressed. Conclusions: Dual checkpoint blockade using nivo/ipi has a prominent immunomodulatory role in extensive stage SCLC characterized by increased local adaptive immune responses, reduced HLA class-I antigen presentation and change in the molecular subtype in a subset of cases. We identified genomic features associated with treatment sensitivity/resistance. Clinical trial information: NCT03670056 .

Efficacy and safety of durvalumab + chemotherapy vs. atezolizumab + chemotherapy in the treatment of small‑cell lung cancer: a retrospective comparative cohort study.

Durvalumab and atezolizumab have recently been approved in extensive small cell lung cancer (SCLC) with moderate median overall survival (OS) improvements. However, only limited data exist regarding the impact of immunotherapy in real-world SCLC patients. This study sought to assess the efficacy and safety of atezolizumab plus chemotherapy and durvalumab plus chemotherapy in the treatment of SCLC in a real-world setting. A retrospective cohort study of all patients treated for SCLC with chemotherapy with PD-L1 inhibitor, at 3 centers in China between February 1, 2020 and April 30, 2022. Patient characteristics, adverse-events and survival analyses were conducted. A total of 143 patients were enrolled in this study, 100 were treated with durvalumab and the remainder with atezolizumab. The baseline characteristics of the two groups were fundamentally balanced before using PD-L1 inhibitors (P>0.05). The median OS (mOS) of the patients who received durvalumab or atezolizumab as the first-line treatment were 22.0 and 10.0 months, respectively (P=0.03). Survival analysis of patients with brain metastasis (BM) revealed that the median progression-free survival (mPFS) of patients without BM treated with durvalumab plus chemotherapy (5.5 months) was longer than that of those with BM (4.0 months) (P=0.03). In contrast, in the atezolizumab plus chemotherapy regimen, BM did not affect survival. In addition, the addition of radiotherapy to treatment with PD-L1 inhibitors in combination with chemotherapy has a tendency to improve long-term survival. As for safety analysis, there was no significant difference in the incidence of immune-related adverse events (IRAEs) during PD-L1 inhibitor therapy between the 2 groups (P>0.05). And during treatment with immunochemotherapy, radiotherapy was not associated with the development of IRAE (P=0.42) but increased the risk of immune-related pneumonitis (P=0.026). The implication of this study for clinical practice is a preference for durvalumab in first-line immunotherapy for SCLC. In addition, appropriate radiotherapy during treatment with PD-L1 inhibitors in combination with chemotherapy may prolong long-term survival, but the occurrence of immune-related pneumonitis should be vigilant. Data from this study are limited and the baseline characteristics of the two populations still need to be more finely classified.

The prognostic value of patient reported outcomes (PROs) and clinical/demographic variables in the CASPIAN study.

8516 Background: PROs have been shown to predict outcomes in non-small cell lung cancer and, using the FACT-G PRO instrument, in extensive stage small cell lung cancer (ES-SCLC). This study explored the relationships between EORTC QLQ-C30 domains and overall survival (OS) and progression free survival (PFS) in the phase III ES-SCLC CASPIAN trial, with and without adjustments for treatment (tx) and baseline clinical and demographic variables. Methods: CASPIAN had 3 treatment arms: durvalumab plus platinum–etoposide; durvalumab plus tremelimumab plus platinum–etoposide; and platinum–etoposide alone. It included the EORTC QLQ-C30, a PRO instrument consisting of 5 functioning scales (physical, role, emotional, cognitive, social), a global health status/quality of life (QoL) scale, 3 symptom scales (fatigue, nausea/vomiting, pain), 5 single item symptom assessments (dyspnea, insomnia, appetite loss, constipation, diarrhea) and a single financial difficulties item. Higher functional and QoL scores indicate better health status/function (anticipated positive OS/PFS associations) while higher symptom and financial difficulty scores represent a greater burden (anticipated negative OS/PFS associations). Baseline PRO scores were pooled across the 3 CASPIAN arms to obtain the most PRO information and used in 3 Cox proportional hazard models for OS and PFS: (A) scores only, (B) scores with a tx category for each CASPIAN arm, and (C) scores with tx categories and other baseline covariates (sex, age [ &lt; 65, ≥65], ECOG performance status [0, &gt; = 1], smoker [Y/N], CNS metastasis [Y/N], race [Asian, non-Asian], stage [III, IV], region [Asia, Europe, North and South America]). Models B and C were stratified by the type of platinum received. Backwards selection found the set of variables most associated with OS and PFS. There was no correction for multiplicity and nominal P-values &lt; 0.05 were used to assess importance. Results: The outcomes and models associated with more favorable baseline PRO scale/item scores were: (i) better OS and PFS across all 3 Cox models [physical, role, social, QoL, fatigue, pain]; (ii) better OS [emotional (models A,C), nausea/vomiting (model C), dyspnea (model C)], and (iii) better PFS [emotional (model C), financial difficulties (models A,B,C)]. Among the 90 estimated Cox hazard ratios, 82 had the anticipated directions for OS and PFS with 54/90 of the estimates having P &lt; 0.05. In each Cox model, more favorable baseline diarrhea scores were associated with reduced OS. All 15 baseline PRO score domains for OS and 10/15 for PFS were important in the stepwise selection process. Conclusions: The results largely indicate that baseline PROs had prognostic value in the CASPIAN trial across different specifications, some including tx and baseline clinical and demographic values. A better understanding of the relationship between tx and PROs may aid tx decisions. Clinical trial information: NCT03043872 .