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Asieh Golozar
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EP1.12 - Small Cell Lung Cancer/NET (ID 202)
- Event: WCLC 2019
- Type: E-Poster Viewing in the Exhibit Hall
- Track: Small Cell Lung Cancer/NET
- Presentations: 2
- Now Available
- Moderators:
- Coordinates: 9/08/2019, 08:00 - 18:00, Exhibit Hall
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EP1.12-19 - Characteristics of Patients with Small-Cell Lung Cancer in the Real-World: A Systematic Review (Now Available) (ID 1842)
08:00 - 18:00 | Presenting Author(s): Asieh Golozar
- Abstract
Background
Patients with poor performance status (PS) ≥2 are generally underrepresented in clinical trials. Describing patients’ characteristics outside clinical trials setting would help better characterize unmet needs. This study aimed to assess the characteristics of SCLC patients, overall and according to sub-types; extensive-stage (ES) and limited-stage (LS).
Method
A systematic review of observational studies was conducted using MEDLINE and Embase databases between January 1998 and October 2018. Pragmatic searches of the grey literature were conducted to identify additional sources. Studies reporting epidemiological data on SCLC were independently screened, adjudicated and data were abstracted by two assessors, with conflicts resolved by a third.
Result
Of the 2,418 sources identified, 394 were reviewed in depth and 140 were retained. An additional 28 sources were identified through pragmatic searches yielding a total of 168. Median age at diagnosis (reported in 32 studies) ranged from 54 to 74 years. Sex distribution was reported in 86 studies, with a male predominance irrespective of stage. Eastern Cooperative Oncology Group PS was reported in 30 studies. The majority of studies were hospital-based (n=28, 93%) and data mainly originated from medical records or chart review (22, 73%). PS was assessed at baseline or at the time of diagnosis in 26 studies. Twenty-three (77%) studies reported poor PS status for ≥25% of the SCLC population, with six reporting poor PS in ≥50% of the SCLC population. The proportion of SCLC patients with poor PS ranged from 14% to 88%. Findings were heterogeneous across studies due to the variability in thresholds used to define the categories, study setting and inclusion of both LS- and ES-SCLC patients for reporting. For studies reporting PS by stage (n=4), the proportion of patients with poor PS ranged from 13% to 53% in ES-SCLC and 11% to 12% in LS-SCLC.
Conclusion
A significant percentage of patients with SCLC outside clinical trials present with a poor PS. LS-SCLC patients have a better PS. Prevalence of poor PS was higher for ES-SCLC and the reported figures are higher compared to non-small cell lung cancer.
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EP1.12-39 - Survival and Prognostic Factors in Patients with Small-Cell Lung Cancer: A Systematic Review of Observational Studies (Now Available) (ID 1824)
08:00 - 18:00 | Presenting Author(s): Asieh Golozar
- Abstract
Background
With limited advances in the management of small-cell lung cancer (SCLC) within the past thirty years, SCLC still imposes a substantial burden. Identification of prognostic factors help optimize development of appropriate treatment strategies. As part of a larger systematic review, this study aimed to describe survival and prognostic factors in SCLC.
Method
A systematic review of observational studies was conducted using MEDLINE and Embase over the period 01 January 1998‒17 October 2018. Pragmatic searches of the grey literature, including conference abstracts and proceedings, were also conducted to identify additional sources. Search outputs were independently screened, adjudicated and abstracted by two assessors independently, with conflicts resolved by a third.
Result
Of the 2,418 sources identified in the literature, 394 were retained for full text review, out of which 140 were included. In addition, 28 were identified through pragmatic searches yielding a total of 168 sources. Data mainly originated from Asia-Pacific (51; 42.2%), North America (30; 24.8%) and Europe (29; 24%). Eight different measures of survival were used across 121 studies (102 overall, 40 limited-stage [LS]-SCLC and 42 extensive-stage [ES]-SCLC): median overall survival (OS) was the most commonly reported, followed by 1- and 5-year survival rates. A total of 71/102 (69.6%) studies on SCLC, 19/40 (47.5%) on LS-, and 17/42 (40.5%) on ES-SCLC reported median OS. In SCLC, the median OS ranged from 4.6 to 29.1 months, while it ranged from 10 to 47 months in LS-SCLC and from 4 to 14.2 months in ES-SCLC. Survival trend was reported in three studies using data from SEER registries with a general trend towards an increase in survival rate when 2- and 5-year survival rates were reported. When reported (one source), no improvement in OS trend was noted. Chemotherapy, radiation therapy, prophylactic cranial irradiation, performance status, age and sex were among prognostic factors identified in both stages of SCLC.
Conclusion
SCLC survival rate is low yet variable with significantly lower rates in ES-SCLC and minimal changes in survival trend. Significant variability exists in measurement and reporting SCLC survival and survival trend, thus hampering comparability of findings, syntheses of findings and clinical decision-making.
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OA07 - Precision Medicine Involves Biology and Patients (ID 132)
- Event: WCLC 2019
- Type: Oral Session
- Track: Advanced NSCLC
- Presentations: 1
- Now Available
- Moderators:Silvia Novello, Fabrice Barlesi
- Coordinates: 9/09/2019, 11:00 - 12:30, Copenhagen (1980)
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OA07.02 - LKB1 Mutations in Metastatic Non-Small Cell Lung Cancer (mNSCLC): Prognostic Value in the Real World (Now Available) (ID 902)
11:00 - 12:30 | Author(s): Asieh Golozar
- Abstract
- Presentation
Background
Despite recent advances in treating mNSCLC, many patients fail to respond. Identifying genetic markers may help maximize clinical benefit and avoid unnecessary toxicity. LKB1/STK11 alterations (LKB1m) and co-occurring KRAS mutations/LKB1 loss (KRAS/LKB1) have been associated with poor outcomes in patients treated with immunotherapy (IO). Among chemotherapy-treated patients, however, the prognostic value is less understood. This retrospective study examined LKB1m, KRAS/LKB1 and outcomes in patients with mNSCLC receiving IO (as monotherapy or in combination) or chemotherapy in the real-world setting.
Method
Adult patients with mNSCLC who initiated first line (1L) treatment between Jan 2013 and Jun 2017 and had been profiled with the FoundationOne assay in routine care were enrolled from the Flatiron Health Oncology electronic medical record database. Associations between LKB1m, LKB1/KRAS and overall survival (OS) or progression-free survival (PFS) were evaluated by line of therapy (1L and second line [2L]) according to histology (non-squamous/squamous and non-squamous only) using multivariate Cox proportional hazards models. All analyses were stratified by IO or chemotherapy.
Result
2407 patients (1847 non-squamous) were included; average age was 66.1 years at 1L initiation. 328 (13.6%) patients harbored LKB1m and 157 (6.5%) harbored KRAS/LKB1. Among IO-treated patients in the 2L setting, LKB1m was associated with shorter OS and PFS versus wild type. A similar association was observed in the 1L setting and in the non-squamous only subgroup. In patients receiving chemotherapy, LKB1m was associated with worse outcomes only in the 1L setting. All associations were generally more pronounced among KRAS/LKB1 compared with LKB1m patients.
ConclusionTable. Association between LKB1m and OS or PFS in mNSCLC stratified by IO or chemotherapy and lines of therapy Mutation group LKB1m All mNSCLC Non-Squamous Outcome IO Chemotherapy IO Chemotherapy 1L (n = 270) 2L (n = 670) 1L (n =2,137) 2L (n = 863) 1L (n = 187) 2L (n = 498) 1L (n = 1,687) 2L (n = 683) LKB1m, N (%) 40 (14.8) 111 (16.6) 288 (13.5) 83 (9.6) 38 (20.3) 97 (19.5) 257 (15.2) 75 (11.0) OS Median 341 192 340 350 431 201 356 400 (IQR) (221 – NA) (72 – 523) (284 – 405) (307 – 451) (221 – NA) (73 – 613) (287 – 415) (307 – 453) HR 1.43 1.59 1.40 1.07 1.40 1.67 1.43 1.05 (95% CI) (0.90 – 2.27) (1.25 – 2.03) (1.21 – 1.63) (0.81 – 1.41) (0.84 – 2.32) (1.27 – 2.19) (1.22 – 1.68) (0.78 – 1.42) PFS Median 122 67 136 122 125 68 136 128 (IQR) (83 – 295) (46 – 118) (119 – 146) (97 – 147) (81 – 299) (46 – 114) (122 – 149) (98 – 153) HR 1.43 1.59 1.40 1.07 1.36 1.55 1.38 1.07 (95% CI) (0.90 – 2.27) (1.25 – 2.03) (1.21 – 1.63) (0.81 – 1.41) (0.92 – 2.03) (1.22 – 1.97) (1.20 – 1.59) (0.82 – 1.39) KRAS/LKB1 All mNSCLC Non-squamous IO Chemotherapy IO Chemotherapy 1L (n = 270) 2L (n = 670) 1L (n =2,137) 2L (n = 863) 1L (n = 187) 2L (n = 498) 1L (n = 1,687) 2L (n = 683) KRAS/LKB1, N (%) 17 (6.3) 56 (8.4) 140 (6.6) 42 (4.9) 16 (8.6) 52 (10.4) 133 (7.9) 40 (5.9) OS Median 303 209 356 343 341 230 363 350 (IQR) (222 – NA) (72 – 666) (272 – 450) (254 – 554) (130 – NA) (72 – 666) (284 – 462) (254 – 554) HR 1.46 1.63 1.55 1.27 1.44 1.78 1.61 1.28 (95% CI) (0.74 – 2.86) (1.16 – 2.29) (1.26 – 1.90) (0.87 – 1.84) (0.68 – 3.05) (1.22 – 2.59) (1.29 – 2.00) (0.86 – 1.90) PFS Median 126 67 136 133 174 68 136 133 (IQR) (77 – 291) (46 – 91) (112 – 160) (91 – 190) (72 – 295) (47 – 91) (112 – 160) (91 – 190) HR 1.34 1.81 1.40 1.08 1.34 1.86 1.44 1.05 (95% CI) (0.80 – 2.24) (1.35 – 2.44) (1.16 – 1.68) (0.77 – 1.51) (0.76 – 2.36) (1.35 – 2.57) (1.19 – 1.75) (0.74 – 1.50) Note: Bold text indicates significant results; reference group for LKB1m is LKB1wt; reference group for KRAS/LKB1 is KRASwt/LKB1wt
Median OS and PFS and IQRs are expressed in daysAbbreviations: KRAS mutation/LKB1 loss (KRAS/LKB1), Hazard ratio (HR), Interquartile range (IQR), Confidence interval (CI), Immunotherapy (IO), Overall Survival (OS), Progression-free survival (PFS), Wild type (wt)
LKB1m and LKB1/KRAS were associated with numerically worse OS and PFS in the 1L setting, irrespective of treatment, and in IO-treated patients in the 2L setting. Results of this real-world study support previous clinical findings and suggest unique relevance of these mutations in 1L chemotherapy and for 1L and 2L IO.
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