Impact of number versus location of metastases on survival in stage IV M1b non-small cell lung cancer

Gibson, Allan W.; D’Silva, Adrijana; Tudor, R.; Elegbede, A.; Otsuka, Shannon; Bebb, D. Gwyn; Cheung, Winson Y.

doi:10.1007/s12032-018-1182-8

Cited by 42 publications

(35 citation statements)

References 32 publications

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“…Liver and brain metastases are poor prognostic factors in patients with NSCLC. 8,9 The efficacy of immunotherapy treatment effect in these patient populations has been uncertain, with results from one study suggesting reduced benefit in patients with liver metastases. 10 Consistent with poor prognosis among patients with brain or liver metastases, we observed shorter median OS times among these patients compared with patients without brain or liver metastases.…”

Section: Discussionmentioning

confidence: 99%

“…In this updated analysis from KEYNOTE-189, we evaluated efficacy and safety with approximately 10 additional calendar months of follow-up from the first interim analysis data cutoff date. Extrapulmonary metastases to sites such as the liver and brain frequently occur in metastatic NSCLC and are associated with a poor prognosis 8,9 ; whether such metastases alter the magnitude of benefit with immunotherapy has been uncertain. 10 Therefore, we assessed outcomes among patients with liver/brain metastases.…”

Section: Introductionmentioning

confidence: 99%

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Updated Analysis From KEYNOTE-189: Pembrolizumab or Placebo Plus Pemetrexed and Platinum for Previously Untreated Metastatic Nonsquamous Non–Small-Cell Lung Cancer

Gadgeel

Rodríguez-Abreu

Speranza

et al. 2020

JCO

805

698

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PURPOSE In KEYNOTE-189, first-line pembrolizumab plus pemetrexed-platinum significantly improved overall survival (OS) and progression-free survival (PFS) compared with placebo plus pemetrexed-platinum in patients with metastatic nonsquamous non‒small-cell lung cancer (NSCLC), irrespective of tumor programmed death-ligand 1 (PD-L1) expression. We report an updated analysis from KEYNOTE-189 (ClinicalTrials.gov: NCT02578680 ). METHODS Patients were randomly assigned (2:1) to receive pemetrexed and platinum plus pembrolizumab (n = 410) or placebo (n = 206) every 3 weeks for 4 cycles, then pemetrexed maintenance plus pembrolizumab or placebo for up to a total of 35 cycles. Eligible patients with disease progression in the placebo-combination group could cross over to pembrolizumab monotherapy. Response was assessed per RECIST (version 1.1) by central review. No alpha was assigned to this updated analysis. RESULTS As of September 21, 2018 (median follow-up, 23.1 months), the updated median (95% CI) OS was 22.0 (19.5 to 25.2) months in the pembrolizumab-combination group versus 10.7 (8.7 to 13.6) months in the placebo-combination group (hazard ratio [HR], 0.56; 95% CI, 0.45 to 0.70]). Median (95% CI) PFS was 9.0 (8.1 to 9.9) months and 4.9 (4.7 to 5.5) months, respectively (HR, 0.48; 95% CI, 0.40 to 0.58). Median (95% CI) time from randomization to objective tumor progression on next-line treatment or death from any cause, whichever occurred first (progression-free-survival-2; PFS-2) was 17.0 (15.1 to 19.4) months and 9.0 (7.6 to 10.4) months, respectively (HR, 0.49; 95% CI, 0.40 to 0.59). OS and PFS benefits with pembrolizumab were observed regardless of PD-L1 expression or presence of liver/brain metastases. Incidence of grade 3-5 adverse events was similar in the pembrolizumab-combination (71.9%) and placebo-combination (66.8%) groups. CONCLUSION First-line pembrolizumab plus pemetrexed-platinum continued to demonstrate substantially improved OS and PFS in metastatic nonsquamous NSCLC, regardless of PD-L1 expression or liver/brain metastases, with manageable safety and tolerability.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Updated Analysis From KEYNOTE-189: Pembrolizumab or Placebo Plus Pemetrexed and Platinum for Previously Untreated Metastatic Nonsquamous Non–Small-Cell Lung Cancer

Gadgeel

Rodríguez-Abreu

Speranza

et al. 2020

JCO

805

698

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“…Increasing number of metastatic sites correlates with poorer survival outcomes in this study (Tables 1, 2 and 3). In Stage IV M1b Non-Small Cell Lung cancer, the number of metastases but not the location has been found to have an impact on the survival outcomes of the patients [43]. On the contrary, the number of metastases has no significant effect on survival in prostate cancer patients [44].…”

Section: Discussionmentioning

confidence: 98%

Survival Outcomes of Metastatic Colorectal Cancer Patients in Brunei Darussalam and the Impact of <em>KRAS</em> Mutations

Damit¹,

Patnaik²,

Chaw³

et al. 2020

Preprint

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Colorectal cancer (CRC) is the third most common cancer, with rising incidence due to lifestyle and diet. 40% of CRC cases are found to have KRAS mutations. In this study, we investigate the survival outcome of metastatic Colorectal cancer mCRC) patients in Brunei Darussalam restrospectively. Chi-squared test was used to compare the survival outcomes of mCRC patients, and Mann-Whitney U test was used to compare the median ages of both groups. Kaplan-Meier survival curves were drawn and logrank test was used to compare the survival outcome between two groups. There was a total of 105 patients with stage IV CRC being treated during the study period. 81.6% (n=62) of mCRC patients were found to have the primary tumours on the left side of the colon. 19 of these 26 (73.1%) mutant KRAS mCRC patients died, while 23 of 50 (46.0%) wild-type KRAS mCRC patients died at the end of the study period, contributing to death rates of 45.2% and 54.8%, correspondingly. 30.3% (n=23) of the study population had a single metastatic site detected (either liver, or lung or any other organs), while 69.7% (n=53) of the 76 mCRC patients had two (double) or more metastatic sites. 69.2% (n=18) and 30.8% (n=8) of the mutant KRAS mCRC patients had mutations within codons 12 and 13, respectively. To our knowledge, this is the first study in Brunei Darussalam to analyse both the survival outcomes of metastatic CRC patients and those of mutant KRAS mCRC patients. Chi-squared analysis showed a significant difference between the survival outcomes of wild-type KRAS and mutant KRAS mCRC patients (p-value = 0.024). There was a significant difference in the survival outcome between the mutant KRAS mCRC patients with RCC and mutant KRAS mCRC with LCC patients. There was no significant difference between the survival outcomes of mutant KRAS patients with mutations in either codon 12 or 13 of the KRAS gene (Table 3). However, there is a significant difference in the median survival periods between the mutant KRAS mCRC patients with mutations in codon 12 and those with mutation in codon 13 of the KRAS gene (p-value = 0.003). In conclusion, we found that mutant KRAS mCRC patients had a significantly poorer OS, which was shown to be worse when the primary tumours were found at the left side of the colon. Mutant KRAS mCRC patients with mutations in codon 12 were found to have shorter survival median periods than those with mutations within codon 13.

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“…However, adrenal metastases rarely show severe symptoms and their exact cause is unclear [51]. Some researchers believe that specific organ metastases do not affect the prognosis of lung cancer [25][26][27][28]. And some researchers [28,52] propose that the increase in the number of metastatic organs reflects the ability of tumor cells to adapt to varying tissue microenvironments, resulting in the emergence of drug resistance Table 9 Comparison of overall survival rates between patients with and without STM from lung cancer and shortening of survival time.…”

Section: Overall 1- 3- and 5-year Survival Rates In The Stm And Nonmentioning

confidence: 99%

“…A recent study showed that STM was associated with poor prognosis in lung cancer [7]. However, the prognostic value of specific organ metastases, including STM, is controversial and their effects on lung cancer have not been fully elucidated [24][25][26][27][28].…”

Section: Introductionmentioning

confidence: 99%

Imaging features and prognostic value of 18F-FDG PET/CT detection of soft-tissue metastasis from lung cancer: a retrospective study

Zhang

et al. 2020

BMC Cancer

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Background: Soft-tissue metastasis (STM) is a relatively rare, but not exceptional, manifestation of lung cancer. The purpose of this study was to evaluate the imaging features of STM from lung cancer using fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography (18 F-FDG PET/CT), and assess the impact of STM detected at baseline PET/CT on patient survival. Methods: Out of 4543 patients with lung cancer who underwent 18 F-FDG PET/CT in our hospital between January 2013 and September 2018, 85 were diagnosed with STM (78 at baseline PET/CT and 7 at restaging PET/CT) and included in the imaging study. We conducted a comparative survival analysis between patients with stage 4 lung cancer with and without STM at baseline PET/CT (n = 78 in each group) and performed univariate and multivariate analyses to investigate the factors affecting the prognosis of lung cancer. Results: A total of 219 lesions were identified by 18 F-FDG PET/CT: 215 were detected by PET and 139 by CT. Muscle STM were primarily found in the hip and upper limb muscle, whereas subcutaneous STM were mainly distributed in the chest, abdomen, and back. In 68 patients, STM were found incidentally during routine 18 F-FDG PET/CT staging. Isolated STM were detected in 6 patients, whose tumor staging and treatment were affected by PET/CT findings. There were no significant differences in the 1-, 3-, and 5-year survival rates between patients with and without STM at baseline PET/CT. Brain and adrenal metastases, but not STM, were associated with poor prognosis of stage 4 lung cancer.

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Impact of number versus location of metastases on survival in stage IV M1b non-small cell lung cancer

Abstract: Number rather than location of EPMS is a prognostic factor in patients with stage IV M1b NSCLC. This information is relevant for accurate prognostication, stratification of participants in future clinical trials, and timely and appropriate advanced care planning.

Cited by 42 publications

References 32 publications

Updated Analysis From KEYNOTE-189: Pembrolizumab or Placebo Plus Pemetrexed and Platinum for Previously Untreated Metastatic Nonsquamous Non–Small-Cell Lung Cancer

Updated Analysis From KEYNOTE-189: Pembrolizumab or Placebo Plus Pemetrexed and Platinum for Previously Untreated Metastatic Nonsquamous Non–Small-Cell Lung Cancer

Survival Outcomes of Metastatic Colorectal Cancer Patients in Brunei Darussalam and the Impact of <em>KRAS</em> Mutations

Imaging features and prognostic value of 18F-FDG PET/CT detection of soft-tissue metastasis from lung cancer: a retrospective study

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