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The 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. We 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. Six 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. In 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. • PD-1/PD-L1 inhibitors reduced deaths compared to standard chemotherapy in ES-SCLC. • Their use did not increase the rate of hematological adverse events of any grade. • Their use was linked with decreased appetite, hyponatremia and hypothyroidism [ABSTRACT FROM AUTHOR]

Background: Despite its low incidence rate, small-cell lung cancer (SCLC), which accounts for approximately 10%–15% of all lung cancers, is concerningly characterized by its rapid progression, strong metastatic potential, and high fatality rate. Therefore, an effective predictive model for SCLC treatment is imperative for early intervention. Objective: In this study, we aimed to enhance the cancer stem cell (CSC) capabilities of SCLC through a three-dimensional (3D) culturing approach and to evaluate its potential as a predictive model for therapeutic response in SCLC by transplanting the spheroids into mice. Results: To achieve uniform and scalable production of 3D SCLC spheroids, the SpheroFILM culture platform was employed and the expression of CSC markers was verified at the gene and protein levels within the spheroids cultured onboard. Moreover, spheroids were transplanted into mice to confirm gene and protein expression of CSC markers, tumor-formation capacity, proliferation ability, and invasion potential through histological staining. Conclusion: Based on our results, the transplantation of enhanced CSC-functioning 3D SCLC cell lines into mice led to a significant increase in tumor-formation capacity along with elevated expression of CSC markers. Thus, the results collectively suggest that the augmentation of CSC properties in 3D cultured cell lines, when transplanted into animal models, reduces necrosis and enhances tumor formation, proliferation, and invasion. [ABSTRACT FROM AUTHOR]

Background: Patients with small-cell lung cancer (SCLC) have few treatment options and dismal overall survival (OS) after failed platinum-based chemotherapy. Methods: The eligibility criteria of this phase II clinical trial included patients with measurable disease, age of 18 to 75 years, a confirmed diagnosis of disease progression or recurrence after prior platinum-based chemotherapy with a pathologically proven diagnosis of SCLC. Patients were treated with anlotinib at a dosage of 12 mg once daily (QD) and S-1 at 60 mg twice daily (BID) for 2 weeks, followed by a 1-week treatment-free interval. After six cycles of the above treatment, patients continued the maintenance therapy using S-1 monotherapy at 60 mg/ BID for 2 weeks, followed by a 1-week treatment-free interval until disease progression. Results: From March 2019 to June 2020, a total of 71 patients were initially assessed for eligibility in this study. Out of these, 52 patients who met the inclusion criteria were enrolled, and 48 patients received at least two doses of the study drug. The median follow-up time was 25.1 months. The ORR was seen in 21 patients (43.8%). The median PFS was 4.5 months (95% CI, 3.5–5.5 months), and the median OS was 5.9 months (95% CI, 4.6–7.3 months). The most common grade 3–4 treatment-related adverse events were thrombocytopenia (16.7%), anemia (14.6%), neutropenia (14.6%), and hypertension (10.4%). No treatment-related death occurred. Conclusions: The combination of anlotinib with oral fluoropyrimidine S-1 demonstrated notable activity in relapsed or refractory SCLC, showing a favorable ORR and an acceptable, manageable safety profile. Trial registration: This trial was registered with ClinicalTrial.gov (NCT03823118) on 3 January 2019. [ABSTRACT FROM AUTHOR]

Background and objectives: Second-line treatment for small-cell lung cancer (SCLC) is primarily guided by the time elapsed since the last platinum dose. Rechallenge with carboplatin and etoposide has demonstrated superior outcomes compared to topotecan if the platinum-free interval (PFI) is longer than 90 days and is considered the standard of care. However, these findings predate the chemo-immunotherapy era. This study investigates the effectiveness of the rechallenge strategy after chemo-immunotherapy in a real-world setting. Design and methods: We retrospectively reviewed patients with the extensive stage (ES)-SCLC who received rechallenge with carboplatin and etoposide after first-line chemoimmunotherapy between September 2020 and August 2023 in nine European centres. Demographic and clinical data were collected and analysed. Results: A total of 93 patients were included. Sixty-six (71%) patients had a PFI between 3 and 6 months. Consolidation thoracic radiotherapy and prophylactic cranial irradiation had been administered in 31 (33.3%) patients and 20 (21.5%) patients, respectively. Overall response rate was 59.1%. Median progression-free survival (PFS) was 5 months (95% confidence interval (CI) 4.3–5.7) and median overall survival (OS) was 7 months (95% CI 5.7–8.3). Notably, PFS and OS were not different according to PFI (3–6 m vs > 6 m). Conclusion: Rechallenge with carboplatin and etoposide is a valid second-line option in patients with ES-SCLC whose disease progresses after first-line chemoimmunotherapy. Our analysis shows similar results to previous studies. Furthermore, outcomes were consistent across patients with different PFIs, confirming its efficacy in patients with a PFI longer than 3 months. [ABSTRACT FROM AUTHOR]

Purpose: To compare the efficacy of first‐line regimens based on programmed cell death (or ligand) [PD‐(L)1] blockade in extensive‐stage small‐cell lung cancer (ES‐SCLC) patients with or without liver metastases (LM), and to identify optimal treatment strategies. Methods: Network meta‐analysis of randomized controlled trials (RCTs) comparing chemo‐immunotherapy (CIT) and chemotherapy (CT) in ES‐SCLC patients stratified by LM. Overall survival (OS) and progression‐free survival (PFS) were evaluated using hazard ratios (HRs) and 95% confidence intervals (CIs). Results: Seven RCTs involving 3658 ES‐SCLC patients (1243 with LM, 2415 without LM) were analyzed. For patients with LM, the combination therapies of anti‐PD‐1 + CT (HR, 0.67; 95% CI, 0.54%–0.82%; p < 0.001) and anti‐PD‐L1 + CT + anti‐angiogenesis (HR, 0.84; 95% CI, 0.71%–0.99%; p = 0.042) demonstrated superior efficacy in prolonging OS compared to CT alone. The anti‐PD‐1 + CT regimen had the highest cumulative probability of 91.6% for extending OS in patients with LM. For patients without LM, all CIT regimens resulted in improved OS compared to CT alone, with the regimen of anti‐angiogenesis + anti‐PD‐L1 + CT ranking first and having the highest cumulative probability of 95.5% for prolonging OS. Conclusions: CIT is effective for ES‐SCLC patients regardless of LM status. For patients with LM, PD‐1 blockade combined with CT is the best option. For patients without LM, the most beneficial regimen is the combination of anti‐angiogenesis, PD‐L1 blockade, and CT. [ABSTRACT FROM AUTHOR]

Durvalumab is an IgG1 monoclonal antibody that has efficacy in many advanced-stage cancers, especially in small-cell lung cancer. The efficacy of durvalumab can be enhanced by chemotherapy. Cutaneous side effects due to treatment with durvalumab are usually self-limiting and easily manageable. We present a clinical case of a female patient aged 61, with small-cell lung carcinoma in stage III B, cT3N2M, who developed a disseminated cutaneous vasculitis after seven months of durvalumab monotherapy, having previously been treated with polychemotherapy according to oncological protocols. To the best of our knowledge, based on a comprehensive search in leading databases, like Web of Science, Scopus, PubMed and some others, ours is the first published case of disseminated cutaneous vasculitis as a result of Durvalumab treatment. Anticancer immunotherapy targeting immune checkpoint inhibition (ICI) has transformed the treatment and evolution of patients with multiple varieties of hematologic cancers. In this context, the cutaneous side effects due to immune checkpoint inhibitor therapies are very few in the scientific literature. Based on this need, we have performed a mini-review of cutaneous side effects due to immune checkpoint inhibitor therapies that treat actual aspects in this sense. We also present some artificial intelligence challenges and future perspectives in the combination of human reasoning and reasoning based on Artificial Intelligence for study of the very rare Disseminate cutaneous vasculitis associated with Durvalumab treatment. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the safety, tolerability, and preliminary efficacy of multiple doses of pegylated irinotecan (JK1201I) as a second‐line monotherapy for treating small‐cell lung cancer (SCLC) patients. Methods: According to the "3 + 3" dose‐escalation principle, patients received intravenous JK1201I at 180 or 220 mg/m2 once every 3 weeks for four cycles. Progression‐free survival (PFS), overall survival (OS), median progression‐free survival (mPFS), and median overall survival (mOS) were evaluated. The Kaplan–Meier method was used to analyze PFS and overall OS. Brookmeyer and Crowley's method was used for mPFS and mOS. Results: This study included 29 patients with stage III–IV SCLC (stage IIIa, n = 1; stage IIIb, n = 1; and stage IV, n = 27). Of these, 26 patients were enrolled in the 180 mg/m2 dose group, and 3 patients were enrolled in the 220 mg/m2 dose group. No dose‐limiting toxicity (DLT) was noted during the first 28 days of treatment. Grade 3 or higher adverse events were recorded in the 180 mg/m2 group, including diarrhea (11.5%, 3/26), neutropenia (7.7%, 2/26), and leukopenia (7.7%, 2/26). In the 220 mg/m2 group, one patient (33.3%, 1/3) experienced neutropenia or leukopenia. In the 180 mg/m2 group, 38.5% (10/26) of patients achieved an objective response rate (ORR), with a disease control rate (DCR) of 73.1% (19/26). The mPFS and mOS were 3.4 and 12.1 months, respectively. In the 220 mg/m2 group, one patient had stable disease, and one had progressive disease (PD). The ORR, DCR, mPFS, and mOS were 0% (0/3) and 33.3% (1/3), 2.7 months and 2.7 months, respectively. Conclusion: JK1201I exhibits promising efficacy and relatively low toxicities as a second‐line monotherapy for SCLC, warranting further large‐scale clinical studies to evaluate its efficacy in greater detail. [ABSTRACT FROM AUTHOR]

Objectives: To investigate the association between human leukocyte antigen (HLA) and paraneoplastic neurological syndromes (PNS) with Hu antibodies, and potential specificities according to clinical presentation and cancer status. Methods: HLA genotypes at four-digit resolution were imputed from available genome-wide association data. Allele carrier frequencies were compared between patients (whole cohort, n = 100, and according to clinical presentation and cancer status) and matched healthy controls (n = 508) using logistic regression controlled by the three main principal components. Results: The clinical presentation of 100 anti-Hu patients involved the central nervous system (28, 28%), the peripheral nervous system (36, 36%) or both combined (36, 36%). Cancer diagnosis was certain in 75 (75%). HLA association analyses revealed that anti-Hu PNS patients were more frequently carriers of DQA1*05:01 (39% vs. 19%, OR = 2.8 [1.74–4.49]), DQB1*02:01 (39% vs. 18%, OR = 2.88 [1.79–4.64]) and DRB1*03:01 (41% vs. 19%, OR = 2.92 [1.80–4.73]) than healthy controls. Remarkably, such DR3 ~ DQ2 association was absent in patients with pure central involvement, but more specific to those manifesting with peripheral involvement: DQA1*05:01 (OR = 3.12 [1.48–6.60]), DQB1*02:01 (OR = 3.35 [1.57–7.15]) and DRB1*03:01 (OR = 3.62 [1.64–7.97]); being even stronger in cases with sensory neuropathy, DQA1*05:01 (OR = 4.41 [1.89–10.33]), DQB1*02:01 (OR = 4.85 [2.04–11.53]) and DRB1*03:01 (OR = 5.79 [2.28–14.74]). Similarly, DR3 ~ DQ2 association was only observed in patients with cancer. Discussion: Patients with anti-Hu PNS show different HLA profiles according to clinical presentation and, probably, cancer status, suggesting pathophysiological differences. [ABSTRACT FROM AUTHOR]

Objective: Our purpose was to investigate the clinicopathological diagnostic value of immunohistochemical antibody for insulinoma-associated protein 1 (INSM1) in biopsy specimens of SCLC. Methods: Biopsy specimens of SCLC diagnosed at the pathology department of Tangshan Gongren Hospital from January 2022 to June 2023 were selected. INSM1 expression was detected and compared with conventional neuroendocrine markers synaptophysin (SYP), chromogranin A (CHGA), and CD56 regarding expression sensitivity and specificity. Results: The sensitivity of INSM1 expression was significantly higher than that of CHGA (95% vs 50%, P =.000), but there was no statistically significant difference in the specificity of INSM1, SYP, CHGA, and CD56 expression (100% vs 94% vs 98% vs 92%, respectively, P =.241, 1.000,.126). Conclusions: INSM1 antibody shows high sensitivity and specificity in the expression of SCLC and serves as a reliable immunohistochemical marker in the clinicopathological diagnosis of SCLC in biopsy specimens. [ABSTRACT FROM AUTHOR]

Small-cell lung cancer (SCLC) is the most aggressive and lethal type of lung cancer, characterized by limited treatment options, early and frequent metastasis. However, the determinants of metastasis in SCLC are poorly defined. Here, we show that estrogen-related receptor gamma (ERRγ) is overexpressed in metastatic SCLC tumors, and is positively associated with SCLC progression. ERRγ functions as an essential activator of extracellular matrix (ECM) remodeling and cell adhesion, two critical steps in metastasis, by directly regulating the expression of major genes involved in these processes. Genetic and pharmacological inhibition of ERRγ markedly reduces collagen production, cell-matrix adhesion, microfilament production, and eventually blocks SCLC cell invasion and tumor metastasis. Notably, ERRγ antagonists significantly suppressed tumor growth and metastasis and restored SCLC vulnerability to chemotherapy in multiple cell-derived and patient-derived xenograft models. Taken together, these findings establish ERRγ as an attractive target for metastatic SCLC and provide a potential pharmacological strategy for treating this lethal disease. Synopsis: Metastasis remains the leading cause of mortality in patients with small cell lung cancer (SCLC). Through single-cell, bulk transcriptome analysis and gene functional studies, ERRγ was identified as a key player of extracellular matrix (ECM) remodelling and a promising target for metastatic SCLC. ERRγ was overexpressed in metastatic SCLC tumors and positively correlated with disease progression. ERRγ was identified as a key determinant of ECM-related gene expression in SCLC cells. Genetic and pharmacological suppression of ERRγ reduced collagen production, cell-matrix adhesion, and suppressed microfilament formation, thereby halting SCLC cell invasion and metastatic dissemination. ERRγ antagonists suppressed SCLC tumor growth and metastasis, and restored the sensitivity of resistant SCLC to chemotherapy. Metastasis remains the leading cause of mortality in patients with small cell lung cancer (SCLC). Through single-cell, bulk transcriptome analysis and gene functional studies, ERRγ was identified as a key player of extracellular matrix (ECM) remodelling and a promising target for metastatic SCLC. [ABSTRACT FROM AUTHOR]

Simple Summary: Although the high mutation burden in small-cell lung cancer (SCLC) suggests that it should be responsive to immune checkpoint blockade (ICB), relatively few patients have shown durable clinical benefit (DCB). To identify biomarkers of responses, biopsies from 35 patients treated with ICB (21 first-line and 14 second-line) were subjected to transcriptomic analysis and gene signatures were studied. Patients with DCB were compared to those with no clinical benefit (NCB). The response to ICB in the second-line, but not the first-line, setting was associated with gene signatures of inflammation, antigen presentation, interferon responses, and increased CD8 T cells. Our data suggest that responses to ICB in the second-line setting can be predicted by the baseline inflammatory state of the tumor; however, this strong association with inflammation was not observed in the first-line setting, likely because chemotherapy alters the immune milieu allowing a response to ICB. 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. [ABSTRACT FROM AUTHOR]

Background: Usage of immune checkpoint inhibitors (ICIs) has prolonged the overall survival (OS) of patients with extensive‐stage small‐cell lung cancer (ES‐SCLC). In clinical trials, males accounted for a large proportion, leading to the uncertainty of its efficacy in female patients. We therefore conducted this study to explore the efficacy and safety of using ICIs in female patients with ES‐SCLC. Methods: We retrospectively enrolled female SCLC patients and subdivided them into two groups. Group A (n = 40) was defined as ES‐SCLC patients who received first‐line standard chemotherapy with or without ICIs. Group B (n = 47) included relapsed SCLC patients who were administered with second‐line therapies. Kaplan–Meier methodology was used to calculate survival analysis. Chi‐squared tests were used to analyze the incidence of adverse events (AEs). Results: Median progression‐free survival (PFS) and median OS favored the ICI‐contained cohorts (Group A PFS: 8.3 vs. 6.1 months; OS: not reached vs. 11.3 months; Group B PFS: 15.1 vs. 3.3 months; OS: 35.3 vs. 8.3 months), especially in those patients who received second‐line immunotherapies. Patients who received immunotherapy had a slightly higher incidence rate of grade ≥3 AEs (Group A: 71.4% vs. 46.2%; Group B: 44.5% vs. 13.2%). Those who developed grade ≥3 AEs in first‐line ICIs cohort had a more favorable survival (PFS: 8.3 vs. 3.2 months; OS: not reached vs. 5.1 months). Conclusions: Our study suggested that female ES‐SCLC patients treated with immunotherapy tended to achieve a relatively longer survival. The incidence of AEs (grade ≥3) was higher in women patients receiving ICIs, which requires monitoring more closely. [ABSTRACT FROM AUTHOR]

Background: Small-cell lung cancer (SCLC) is a leading cause of cancer-related death. However, the prognostic value of the tumor shrinkage rate (TSR) after chemotherapy for SCLC is still unknown. Methods: We performed a retrospective analysis of 235 patients with SCLC. The TSR cutoff was determined based on receiver-operating characteristic curve analysis. The associations of TSR with progression-free survival (PFS) and overall survival (OS) were assessed using univariate and multivariate Cox proportional hazards models. Survival curves were obtained by the Kaplan–Meier method and compared using the log-rank test. Recurrence patterns after first-line treatment were summarized in a pie chart. A nomogram was constructed to validate the predictive role of the TSR in SCLC. Results: The TSR cutoff was identified to be − 6.6%. Median PFS and OS were longer in the group with a TSR < –6.6% than in the group with a TSR ≥ − 6.6%. PFS and OS were also longer in patients with extensive SCLC when the TSR was < − 6.6% than when it was > − 6.6%. Brain metastasis-free survival was better in the group with a TSR < − 6.6%. There was a significant positive correlation between TSR and PFS. Furthermore, univariate and multivariate regression analyses showed that the TSR, patient age, and previous radiotherapy were independent prognostic factors for OS while TSR and M stage were independent prognostic factors for PFS. Conclusions: The TSR may prove to be a good indicator of OS and PFS in patients receiving chemotherapy-based first-line treatment for SCLC. [ABSTRACT FROM AUTHOR]

Introduction: Small-cell lung cancer (SCLC) is an aggressive form of cancer with a poor prognosis. The two-year survival rate is 8% of all cases. Case presentation: We present the case of a male patient who was 50 years old at the time of diagnosis in May 2022. He was diagnosed with extensive-stage small-cell lung cancer, treated with immunotherapy in combination with chemotherapy (Durvalumab in combination with Etoposide plus Carboplatin) as a first-line treatment, followed by maintenance immunotherapy. In December 2023, a PET-CT scan revealed progressive disease with multiple metastases. Chemotherapy was reinitiated with Etoposide plus Cisplatin in January 2024. After two cycles of chemotherapy, the patient developed post-chemotherapy anemia, for which treatment with Epoetinum alpha was initiated. Chemotherapy was continued for another five cycles, until May 2024, with the maintenance of hemoglobin at a level within 9.9 mg/dL–11 mg/dL. Upon assessment at the end of May 2024, the patient presented an ECOG = 2 performance status, with a moderate general state, moderate-intensity fatigue, no pain, no anxiety or depression and no dyspnea. Discussions, Literature Review and Conclusions: Reinitiating chemotherapy after the failure of maintenance immunotherapy may be an option in patients with SCLC. Epoetinum allows oncological treatment by preventing chemotherapy-induced anemia. [ABSTRACT FROM AUTHOR]

Abstract Background Patients with small-cell lung cancer (SCLC) have few treatment options and dismal overall survival (OS) after failed platinum-based chemotherapy. Methods The eligibility criteria of this phase II clinical trial included patients with measurable disease, age of 18 to 75 years, a confirmed diagnosis of disease progression or recurrence after prior platinum-based chemotherapy with a pathologically proven diagnosis of SCLC. Patients were treated with anlotinib at a dosage of 12 mg once daily (QD) and S-1 at 60 mg twice daily (BID) for 2 weeks, followed by a 1-week treatment-free interval. After six cycles of the above treatment, patients continued the maintenance therapy using S-1 monotherapy at 60 mg/ BID for 2 weeks, followed by a 1-week treatment-free interval until disease progression. Results From March 2019 to June 2020, a total of 71 patients were initially assessed for eligibility in this study. Out of these, 52 patients who met the inclusion criteria were enrolled, and 48 patients received at least two doses of the study drug. The median follow-up time was 25.1 months. The ORR was seen in 21 patients (43.8%). The median PFS was 4.5 months (95% CI, 3.5–5.5 months), and the median OS was 5.9 months (95% CI, 4.6–7.3 months). The most common grade 3–4 treatment-related adverse events were thrombocytopenia (16.7%), anemia (14.6%), neutropenia (14.6%), and hypertension (10.4%). No treatment-related death occurred. Conclusions The combination of anlotinib with oral fluoropyrimidine S-1 demonstrated notable activity in relapsed or refractory SCLC, showing a favorable ORR and an acceptable, manageable safety profile. Trial registration This trial was registered with ClinicalTrial.gov (NCT03823118) on 3 January 2019.

The discovery of targetable mutations in non-small-cell lung cancer (NSCLC) has opened up a plethora of therapeutic options. Epidermal growth factor receptor (EGFR) mutations are found in 10%–20% of NSCLC; however, it is extremely rare in small-cell lung cancer (SCLC), and the efficacy of EGFR tyrosine kinase inhibitors (TKIs) in SCLC is unclear. Here, we describe the case of a 57-year-old nonsmoker lady who was diagnosed with metastatic SCLC. She received multiple lines of palliative chemotherapy. She was deemed unfit for further chemotherapy and immunotherapy and was started on tablet erlotinib empirically. On follow-up imaging with positron emission tomography-computed tomography, she had a partial response and has currently on erlotinib for 2.5 years without disease progression. Although cases with transformation of EGFR-mutated NSCLC to SCLC have been observed, de novo EGFR mutation in SCLC is infrequent. It has been observed that de novo EGFR mutation in SCLC is associated with females, non-smokers, and patients in the eastern part of the world. The current guidelines do not recommend molecular testing for EGFR mutations in SCLC. We described a case of SCLC who had a response to TKI and such cases warrant an answer to whether EGFR mutation testing should be recommended in nonsmoker, females with SCLC, or for them who have failed the first line of chemotherapy.