Small Cell Research Articles

1793P Treatment and outcomes of limited disease small cell lung cancer (LD-SCLC) in the Canadian small cell lung cancer database (CASCADE)

1793P Treatment and outcomes of limited disease small cell lung cancer (LD-SCLC) in the Canadian small cell lung cancer database (CASCADE)

Risk factors and nomograms for diagnosis and early death in patients with combined small cell lung cancer with distant metastasis: a population-based study.

Combined small cell lung cancer (CSCLC) with distant metastasis (DM) is an aggressive disease with a poor prognosis. Effective nomograms are needed to predict DM and early death in patients with CSCLC and DM. This retrospective study included patients with CSCLC from the Surveillance, Epidemiology, and End Results database between 2004 and 2015. Risk factors for DM and early death were analyzed by univariate and multivariate logistic regression. Nomograms were constructed based on the results in a training cohort and confirmed in a validation cohort, and their performances were assessed by concordance index (C-index), receiver operating characteristic curve (ROC), calibration curve, and decision curve analysis (DCA). A total of 788 patients with CSCLC were selected, including 364 patients with metastatic CSCLC. Sex, tumor site, T stage, and N stage were independent risk factors for DM, while age, surgery, chemotherapy, and liver metastasis were independent risk factors for early death. C-index, ROC, calibration, and DCA curve analyses all showed good predictive performances for both nomograms. These nomograms could reliably predict DM risk in CSCLC patients and early death in CSCLC patients with DM, and may thus help clinicians to assess these risks and implement individualized therapies.

A retrospective evaluation of therapeutic efficacy and safety of chemoradiotherapy in older patients (aged ≥ 75 years) with limited-disease small cell lung cancer: insights from two institutions and review of the literature.

The standard treatment for patients in good general condition with limited-disease small cell lung cancer (LD-SCLC) is concurrent platinum/etoposide chemotherapy and thoracic radiotherapy (TRT). However, the efficacy and safety of chemoradiotherapy (CRT) in older patients with LD-SCLC has not been fully explored; moreover, the optimal treatment for this patient group remains unclear. This study aimed to investigate the feasibility and efficacy of CRT in older patients with LD-SCLC. From April 2007 to June 2021, consecutive older patients (aged ≥ 75 years) with stage I to III SCLC who received concurrent or sequential CRT at two institutions were retrospectively evaluated for efficacy and toxicity of CRT. A total of 32 older patients underwent concurrent (n = 19) or sequential (n = 13) CRT for LD-SCLC. The median ages of the patients in the concurrent and sequential CRT groups were 77 (range: 75-81) years and 79 (range: 76-92) years, respectively. The median number of chemotherapeutic treatment cycles was four (range, 1-5), and the response rate was 96.9% in all patients (94.7% in concurrent and 100% in sequential CRT groups). The median progression-free survival (PFS) and median overall survival (OS) for all patients were 11.9 and 21.1 months, respectively. The median PFS was 13.0 and 9.0 months in the concurrent CRT and sequential CRT groups, respectively, with no statistically significant difference (p = 0.67). The median OS from the initiation of CRT was 19.2 and 23.5 months in the concurrent and sequential CRT groups, respectively (p = 0.46). The frequencies of Grade ≥ 3 hematological adverse events were as follows: decreased white blood cell count, 20/32 (62.5%); decreased neutrophil count, 23/32 (71.9%); anemia, 6/32 (18.8%); decreased platelet count, 7/32 (21.9%); and febrile neutropenia, 3/32 (9.4%). Treatment-related deaths occurred in one patient from each group. Although hematological toxicities, particularly reduced neutrophil count, were severe, CRT showed favorable efficacy in both concurrent and sequential CRT groups. However, concurrent CRT may not be feasible for all older patients with LD-SCLC; accordingly, sequential CRT may be considered as a treatment of choice for these patients. Further prospective trials are warranted to identify optimal treatment strategies for this patient group.

1802P Cost-effectiveness study of atezolizumab (ATZ) vs. durvalumab (DUR) in elderly extensive disease small cell lung cancer (ED-SCLC) patients (pts): Real-world data (RWD) on first-line chemotherapy combined with immune-checkpoint inhibitors (Chemo-ICIs)

1802P Cost-effectiveness study of atezolizumab (ATZ) vs. durvalumab (DUR) in elderly extensive disease small cell lung cancer (ED-SCLC) patients (pts): Real-world data (RWD) on first-line chemotherapy combined with immune-checkpoint inhibitors (Chemo-ICIs)

1807P Spatial analyses revealed MMP7 as the biomarker of tumor boundary correlated with immune resistance in small cell lung cancer

1807P Spatial analyses revealed MMP7 as the biomarker of tumor boundary correlated with immune resistance in small cell lung cancer

Bromodomain Protein-directed Agents and MYC in Small Cell Lung Cancer.

Small cell lung cancer (SCLC) has a dismal prognosis. In addition to the inactivation of the tumor suppressors TP53 and RB1, tumor-promoting MYC and paralogs are frequently overexpressed in this neuroendocrine carcinoma. SCLC exhibits high resistance to second-line chemotherapy and all attempts of novel drugs and targeted therapy have failed so far to achieve superior survival. MYC and paralogs have key roles in the oncogenic process, orchestrating proliferation, apoptosis, differentiation, and metabolism. In SCLC, MYC-L and MYC regulate the neuroendocrine dedifferentiation of SCLC cells from Type A (ASCL1 expression) to the other SCLC subtypes. Targeting MYC to suppress tumor growth is difficult due to the lack of suitable binding pockets and the most advanced miniprotein inhibitor Omomyc exhibits limited efficacy. MYC may be targeted indirectly via the bromodomain (BET) protein BRD4, which activates MYC transcription, by specific BET inhibitors that reduce the expression of this oncogenic driver. Here, novel BET-directed Proteolysis Targeting Chimeras (PROTACs) are discussed that show high antiproliferative activity in SCLC. Particularly, ARV-825, targeting specifically BRD4, exhibits superior cytotoxic effects on SCLC cell lines and may become a valuable adjunct to SCLC combination chemotherapy.

Durvalumab with etoposide and carboplatin for patients with extensive-stage small cell lung cancer and interstitial lung disease: A multicenter, open-label prospective trial

ObjectivesCertain guidelines recommend caution when administering immunotherapy in patients with pre-existing interstitial lung disease (ILD) owing to the high incidence of pneumonitis induced by anti-cancer therapy. A prospective clinical trial assessing the safety of chemoimmunotherapy in patients with small-cell lung cancer (SCLC) and pre-existing ILD is warranted. Therefore, this study evaluated the safety and efficacy of chemoimmunotherapy in patients with extensive-stage (ES)-SCLC and mild idiopathic interstitial pneumonia (IIP). MethodsIn this multicenter prospective trial, patients with ES-SCLC and pre-existing mild chronic fibrosing IIP were recruited. Mild IIP was defined as the exclusion of poor pulmonary function, a definite usual interstitial pneumonia (UIP) pattern, and positivity for autoantibodies in blood tests. The patients received durvalumab, etoposide, and carboplatin every three weeks (induction phase) followed by 1,500 mg durvalumab every four weeks (maintenance phase). The primary endpoint was severe pneumonitis-free rate. ResultsTwenty-one patients were included in the analysis. Among them, 13 patients displayed a probable UIP pattern, whereas eight patients exhibited an indeterminate for UIP pattern. Two patients (9.5 %) had pneumonitis of any grade during the induction phase; one had Grade 1 and the other had Grade 5 pneumonitis. No other patient developed pneumonitis during the maintenance phase. The severe pneumonitis-free rate was 95.2 % (95 % confidence interval (CI): 77.3–99.2 %). The median progression-free survival was 5.5 months (95 % CI: 3.6–6.4 months). Median overall survival was 10.7 months (95 % CI: 6.0 months to not reached). ConclusionsChemoimmunotherapy is a feasible treatment approach for patients with ES-SCLC and mild IIP.

1812TiP IDeate-Lung03: A Phase Ib/II study of ifinatamab deruxtecan (I-DXd) plus atezolizumab (atezo) with or without carboplatin (carbo) as first-line (1L) induction or maintenance in patients (pts) with extensive stage (ES) small cell lung cancer (SCLC)

1812TiP IDeate-Lung03: A Phase Ib/II study of ifinatamab deruxtecan (I-DXd) plus atezolizumab (atezo) with or without carboplatin (carbo) as first-line (1L) induction or maintenance in patients (pts) with extensive stage (ES) small cell lung cancer (SCLC)

1813TiP Debio 0123, a highly selective WEE1 inhibitor, combined with carboplatin (CP) and etoposide (ETOP) in patients (pts) with small cell lung cancer (SCLC) that progressed after platinum-based therapy: A phase I dose escalation and expansion study

1813TiP Debio 0123, a highly selective WEE1 inhibitor, combined with carboplatin (CP) and etoposide (ETOP) in patients (pts) with small cell lung cancer (SCLC) that progressed after platinum-based therapy: A phase I dose escalation and expansion study

Netrin-1 and UNC5B Cooperate with Integrins to Mediate YAP-Driven Cytostasis.

Netrins are widely perceived as procancer proteins; however, we uncover an anticancer function for Netrin-1 and its receptor UNC5B.

The expression of YAP1 and other transcription factors contributes to lineage plasticity in combined small cell lung carcinoma.

Lineage plasticity in small cell lung carcinoma (SCLC) causes therapeutic difficulties. This study aimed to investigate the pathological findings of plasticity in SCLC, focusing on combined SCLC, and elucidate the involvement of YAP1 and other transcription factors. We analysed 100 surgically resected SCLCs through detailed morphological observations and immunohistochemistry for YAP1 and other transcription factors. Component-by-component next-generation sequencing (n = 15 pairs) and immunohistochemistry (n = 35 pairs) were performed on the combined SCLCs. Compared with pure SCLCs (n = 65), combined SCLCs (n = 35) showed a significantly larger size, higher expression of NEUROD1, and higher frequency of double-positive transcription factors (p = 0.0009, 0.04, and 0.019, respectively). Notably, 34% of the combined SCLCs showed morphological mosaic patterns with unclear boundaries between the SCLC and its partner. Combined SCLCs not only had unique histotypes as partners but also represented different lineage plasticity within the partner. NEUROD1-dominant combined SCLCs had a significantly higher proportion of adenocarcinomas as partners, whereas POU2F3-dominant combined SCLCs had a significantly higher proportion of squamous cell carcinomas as partners (p = 0.006 and p = 0.0006, respectively). YAP1 expression in SCLC components was found in 80% of combined SCLCs and 62% of pure SCLCs, often showing mosaic-like expression. Among the combined SCLCs with component-specific analysis, the identical TP53 mutation was found in 10 pairs, and the identical Rb1 abnormality was found in 2 pairs. On immunohistochemistry, the same abnormal p53 pattern was found in 34 pairs, and Rb1 loss was found in 24 pairs. In conclusion, combined SCLC shows a variety of pathological plasticity. Although combined SCLC is more plastic than pure SCLC, pure SCLC is also a phenotypically plastic tumour. The morphological mosaic pattern and YAP1 mosaic-like expression may represent ongoing lineage plasticity. This study also identified the relationship between transcription factors and partners in combined SCLC. Transcription factors may be involved in differentiating specific cell lineages beyond just 'neuroendocrine'.

1787P Intracranial response in patients (pts) with baseline (BL) brain metastases (BM) and extensive-stage (ES) small cell lung cancer (SCLC) treated with ifinatamab deruxtecan (I-DXd) in the IDeate-Lung01 study

1787P Intracranial response in patients (pts) with baseline (BL) brain metastases (BM) and extensive-stage (ES) small cell lung cancer (SCLC) treated with ifinatamab deruxtecan (I-DXd) in the IDeate-Lung01 study

Real-World Outcomes of First-Line Treatment With Anti–PD(L)1-Based Combination Therapy for Nonsquamous Metastatic Non–Small Cell Lung Cancer: A Multiregional Chart Review in Europe, Japan, and the United States

Real-World Outcomes of First-Line Treatment With Anti–PD(L)1-Based Combination Therapy for Nonsquamous Metastatic Non–Small Cell Lung Cancer: A Multiregional Chart Review in Europe, Japan, and the United States

1796P Smoking-related genomic mutation patterns in patients with small cell lung cancer treated in ASTRUM-005 study

1796P Smoking-related genomic mutation patterns in patients with small cell lung cancer treated in ASTRUM-005 study

1805P PKD1L1 mutations in small cell lung cancer: A genomic signature for poor prognosis and drug susceptibility

1805P PKD1L1 mutations in small cell lung cancer: A genomic signature for poor prognosis and drug susceptibility

1786O BMS-986012 (anti-fucosyl-monosialoganglioside-1 [fuc-GM1]) with carboplatin + etoposide + nivolumab (CE/NIVO) as first-line (1L) therapy in extensive-stage small cell lung cancer (ES-SCLC): Interim analysis (IA) of a randomized phase II study

1786O BMS-986012 (anti-fucosyl-monosialoganglioside-1 [fuc-GM1]) with carboplatin + etoposide + nivolumab (CE/NIVO) as first-line (1L) therapy in extensive-stage small cell lung cancer (ES-SCLC): Interim analysis (IA) of a randomized phase II study

Phase 2 dose-ranging study to evaluate the efficacy and safety of liposomal irinotecan (LY01610) as a second-line treatment for patients with relapsed small cell lung cancer

This was a multicenter, single-arm dose-ranging phase 2 study aimed to assess the efficacy and safety of LY01610, a liposomal irinotecan, at various doses for patients with relapsed small cell lung cancer (SCLC). This study (NCT04381910) enrolled patients with relapsed SCLC at 10 hospitals across China, who have failed with previous platinum-based treatments. LY01610 was administered at doses of 60mg/m2, 80mg/m2, and 100mg/m2. Primary endpoints were investigator-assessed objective response rate (ORR) and investigator-assessed duration of response (DoR). Secondary endpoints included investigator-assessed disease control rate (DCR), investigator-assessed progression-free survival (PFS), overall survival (OS), and safety. From September 3, 2020 to March 3, 2022, a total of 66 patients were enrolled, with 6, 30, and 30 allocated to the 60mg/m2, 80mg/m2, and 100mg/m2 dose groups, respectively, with 68% (45/66) having a chemotherapy-free interval <90 days. In all 66 patients, the ORR was 32% (21/66, 95% confidence interval [CI], 21-44), with a median DoR of 5.2 months (95% CI, 3.0-8.3). Median PFS and OS were 4.0 (95% CI, 2.9-5.5) and 9.7 (95% CI, 7.2-12.3) months, respectively. The ORR of 60mg/m2, 80mg/m2, and 100mg/m2 dose group were 33% (2/6), 33% (10/30), and 30% (9/30), respectively. The median DoR of 60mg/m2, 80mg/m2, and 100mg/m2 dose group were 4.2 (95% CI, 2.8-not reached), 6.9 (95% CI, 2.5-9.9), and 4.0 (95% CI, 2.7-6.8) months, respectively. The incidence of ≥ grade 3 treatment-related adverse events (TRAEs) in the 60mg/m2, 80mg/m2, and 100mg/m2 dose group were 33% (2/6), 47% (14/30), and 50% (15/30), respectively. Themost common≥grade 3 TRAEs of all 66 patients were neutropenia (27%), leukopenia (24%) and anemia (15%). LY01610 exhibited promising clinical efficacy and manageable safety profiles in patients with relapsed SCLC, the 80mg/m2 dose group had the best benefit-risk ratio. This study was supported by Luye Pharma Group Ltd.

1804P Atezolizumab plus chemotherapy followed by atezolizumab plus anlotinib in the first-line treatment for extensive-stage small cell lung cancer: A multicenter, single-arm, prospective real-world study

1804P Atezolizumab plus chemotherapy followed by atezolizumab plus anlotinib in the first-line treatment for extensive-stage small cell lung cancer: A multicenter, single-arm, prospective real-world study

1808P Immunotherapy retreatment with serplulimab versus chemotherapy in extensive-stage advanced small cell lung cancer previously treated with first-line immunotherapy: A real-world retrospective cohort study

1808P Immunotherapy retreatment with serplulimab versus chemotherapy in extensive-stage advanced small cell lung cancer previously treated with first-line immunotherapy: A real-world retrospective cohort study

1791P Thoracic radiotherapy plus maintenance durvalumab after first-line carboplatin and etoposide plus durvalumab in extensive-stage disease small cell lung cancer (ED-SCLC): A multicenter single-arm open-label phase II trial (SAKK 15/19)tle

1791P Thoracic radiotherapy plus maintenance durvalumab after first-line carboplatin and etoposide plus durvalumab in extensive-stage disease small cell lung cancer (ED-SCLC): A multicenter single-arm open-label phase II trial (SAKK 15/19)tle