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our Premium Content: News alerts, weekly reports and conference plannersTEST:MSK-IMPACT
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News alerts, weekly reports and conference planners
Type:
FDA Approved
Related tests:
Evidence Level:
Sensitive: C3 – Early Trials
[EGFR mutation-Lung Cancer-osimertinib]
Source:
Test:
MSK-IMPACT
Title:
Clinical and genomic landscape of EGFR-mutant lung cancers (LCs) with squamous and adenosquamous differentiation.
Published date:
05/25/2023
Excerpt:
CONTRADICTING EVIDENCE: Pts with EGFR+ sq/adenosq LCs exhibit inferior TTD and OS with 1L osimertinib compared to adenocarcinoma controls.
DOI:
10.1200/JCO.2023.41.16_suppl.9129
Evidence Level:
Sensitive: C3 – Early Trials
[TMB-H-Non Small Cell Lung Cancer-durvalumab]
Source:
Test:
MSK-IMPACT
Title:
Analysis of Tumor Mutational Burden, Progression-Free Survival, and Local-Regional Control in Patents with Locally Advanced Non–Small Cell Lung Cancer Treated With Chemoradiation and Durvalumab
Published date:
01/05/2023
Excerpt:
This cohort study included consecutive patients with unresectable locally advanced NSCLC treated with chemoradiation and adjuvant durvalumab...Patients with TMB-high vs TMB-low tumors had markedly lower 24-month LRF (9% [95% CI, 0%-46%] vs 51% [95% CI, 36%-71%]; P = .001) and improved 24-month PFS (66% [95% CI, 54%-84%] vs 27% [95% CI, 13%-40%]; P = .003).
DOI:
10.1001/jamanetworkopen.2022.49591
Evidence Level:
Sensitive: C3 – Early Trials
[HER-2 positive-Biliary Tract Cancer-neratinib]
Source:
Test:
MSK-IMPACT
Title:
Targeting HER2 mutation–positive advanced biliary tract cancers with neratinib: Final results from the phase 2 SUMMIT basket trial.
Published date:
05/26/2022
Excerpt:
25 treatment-refractory patients with metastatic BTC were enrolled (11 cholangiocarcinoma, 10 gallbladder, 4 ampullary cancers). ORR was 16% (95% CI 4.5–36.1%) and CBR was 28% (95% CI 12.1–49.4%). Median PFS and OS were 2.8 (95% CI 1.1–3.7) and 5.4 (95% CI 3.7–11.7) months, respectively. Median PFS for the gallbladder, cholangiocarcinoma and ampulla cohorts was 3.7 (95% CI 0.8–6.4), 1.4 (95% CI 0.5–9.1), and 1.1 (95% CI 1.1–3.8) months, respectively. Corresponding median OS values in these cohorts were 9.8 (95% CI 2.4–NE), 5.4 (95% CI 0.8–16.2), and 5.0 (95% CI 3.7–10.2) months, respectively. Neratinib is tolerable with modest antitumor activity in patients with BTC harboring HER2 mutations.
DOI:
10.1200/JCO.2022.40.16_suppl.4079
Trial ID:
Evidence Level:
Sensitive: C3 – Early Trials
[TP53 mutation-Diffuse Large B Cell Lymphoma-axicabtagene ciloleucel]
Source:
Test:
MSK-IMPACT
Title:
TP53 and CD19-Directed Chimeric Antigen Receptor T-Cell (CAR-T) Therapy in Large B-Cell Lymphoma
Published date:
11/04/2021
Excerpt:
Patients with relapsed/refractory LBCL treated with CD19-CAR-T were included….TP53 genomic alterations were common (28, 37%)….TP53-alterations were also predictive of OS in univariable and multivariable Cox regression (Fig. C-D; 1-year OS in TP53-altered (48% [95% CI 32 – 71]) vs. wild-type (75% [64 – 89]), p = 0.039)....Notably, in TP53-altered LBCL, axicabtagene-ciloleucel therapy was associated with superior OS ...
DOI:
10.1182/blood-2021-145158
Evidence Level:
Sensitive: C3 – Early Trials
[TP53 mutation + NOTCH4 mutation-Non Small Cell Lung Cancer-Immunotherapy]
Source:
Test:
MSK-IMPACT
Title:
TP53 Mutation Status and Biopsy Lesion Type Determine the Immunotherapeutic Stratification in Non-Small-Cell Lung Cancer
Published date:
09/17/2021
Excerpt:
For patients harboring TP53(+), the top five upregulated genes (ZACNN: ZFHX3, ATM, CDKN2A, NOTCH4, and NTRK3) were selected as predictors for screening responders from non-responders. The results indicated that patients harboring ZACNN(+) received more OS benefits from immunotherapy than those harboring ZACNN(−) [ZACNN(+) vs. ZACNN(−) = undefined vs. 8 months, P < 0.0001]...
DOI:
https://doi.org/10.3389/fimmu.2021.732125
Evidence Level:
Sensitive: C3 – Early Trials
[PIK3CA mutation-Non Small Cell Lung Cancer-Immunotherapy]
Source:
Test:
MSK-IMPACT
Title:
TP53 Mutation Status and Biopsy Lesion Type Determine the Immunotherapeutic Stratification in Non-Small-Cell Lung Cancer
Published date:
09/17/2021
Excerpt:
In the primary sample cohort, the top six upregulated genes (ZPAHPN: ZFHX3, PIK3CA, ARID2, HGF, PDGFRA, and NTRK3) and the bottom downregulated gene (KEAP1) were selected as combined predictors for screening responders from non-responders. The results indicated that patients harboring ZPAHPN(+) received more OS benefits than those harboring ZPAHAN(−) or KEAP1(+)...
DOI:
https://doi.org/10.3389/fimmu.2021.732125
Evidence Level:
Sensitive: C3 – Early Trials
[TP53 mutation + ATM mutation-Non Small Cell Lung Cancer-Immunotherapy]
Source:
Test:
MSK-IMPACT
Title:
TP53 Mutation Status and Biopsy Lesion Type Determine the Immunotherapeutic Stratification in Non-Small-Cell Lung Cancer
Published date:
09/17/2021
Excerpt:
For patients harboring TP53(+), the top five upregulated genes (ZACNN: ZFHX3, ATM, CDKN2A, NOTCH4, and NTRK3) were selected as predictors for screening responders from non-responders. The results indicated that patients harboring ZACNN(+) received more OS benefits from immunotherapy than those harboring ZACNN(−) [ZACNN(+) vs. ZACNN(−) = undefined vs. 8 months, P < 0.0001]...
DOI:
https://doi.org/10.3389/fimmu.2021.732125
Evidence Level:
Sensitive: C3 – Early Trials
[ARID1A mutation-Non Small Cell Lung Cancer-Immunotherapy]
Source:
Test:
MSK-IMPACT
Title:
TP53 Mutation Status and Biopsy Lesion Type Determine the Immunotherapeutic Stratification in Non-Small-Cell Lung Cancer
Published date:
09/17/2021
Excerpt:
The top five altered genes, namely, ARID1A, ZFHX3, ATM, ARID2, and NTRK3, were named AZAAN. Therefore, we evaluated the effect of the predictor-AZAAN on responsive stratification in patients who had received immunotherapy. The results indicated that patients harboring AZAAN(+) received more OS benefits from immunotherapy than those patients harboring AZAAN(−) [AZAAN(+) vs. AZAAN(−): 22 months vs. 10 months, log-rank P value = 0.0006, HR = 0.59]...
DOI:
https://doi.org/10.3389/fimmu.2021.732125
Evidence Level:
Sensitive: C3 – Early Trials
[PDGFRA mutation-Non Small Cell Lung Cancer-Immunotherapy]
Source:
Test:
MSK-IMPACT
Title:
TP53 Mutation Status and Biopsy Lesion Type Determine the Immunotherapeutic Stratification in Non-Small-Cell Lung Cancer
Published date:
09/17/2021
Excerpt:
In the primary sample cohort, the top six upregulated genes (ZPAHPN: ZFHX3, PIK3CA, ARID2, HGF, PDGFRA, and NTRK3) and the bottom downregulated gene (KEAP1) were selected as combined predictors for screening responders from non-responders. The results indicated that patients harboring ZPAHPN(+) received more OS benefits than those harboring ZPAHAN(−) or KEAP1(+)...
DOI:
https://doi.org/10.3389/fimmu.2021.732125
Evidence Level:
Sensitive: C3 – Early Trials
[TP53 mutation + NTRK3 mutation-Non Small Cell Lung Cancer-Immunotherapy]
Source:
Test:
MSK-IMPACT
Title:
TP53 Mutation Status and Biopsy Lesion Type Determine the Immunotherapeutic Stratification in Non-Small-Cell Lung Cancer
Published date:
09/17/2021
Excerpt:
For patients harboring TP53(+), the top five upregulated genes (ZACNN: ZFHX3, ATM, CDKN2A, NOTCH4, and NTRK3) were selected as predictors for screening responders from non-responders. The results indicated that patients harboring ZACNN(+) received more OS benefits from immunotherapy than those harboring ZACNN(−) [ZACNN(+) vs. ZACNN(−) = undefined vs. 8 months, P < 0.0001]...
DOI:
https://doi.org/10.3389/fimmu.2021.732125
Evidence Level:
Sensitive: C3 – Early Trials
[TP53 mutation + ZFHX3 mutation-Non Small Cell Lung Cancer-Immunotherapy]
Source:
Test:
MSK-IMPACT
Title:
TP53 Mutation Status and Biopsy Lesion Type Determine the Immunotherapeutic Stratification in Non-Small-Cell Lung Cancer
Published date:
09/17/2021
Excerpt:
For patients harboring TP53(+), the top five upregulated genes (ZACNN: ZFHX3, ATM, CDKN2A, NOTCH4, and NTRK3) were selected as predictors for screening responders from non-responders. The results indicated that patients harboring ZACNN(+) received more OS benefits from immunotherapy than those harboring ZACNN(−) [ZACNN(+) vs. ZACNN(−) = undefined vs. 8 months, P < 0.0001]...
DOI:
https://doi.org/10.3389/fimmu.2021.732125
Evidence Level:
Sensitive: C3 – Early Trials
[ZFHX3 mutation-Non Small Cell Lung Cancer-Immunotherapy]
Source:
Test:
MSK-IMPACT
Title:
TP53 Mutation Status and Biopsy Lesion Type Determine the Immunotherapeutic Stratification in Non-Small-Cell Lung Cancer
Published date:
09/17/2021
Excerpt:
The top five altered genes, namely, ARID1A, ZFHX3, ATM, ARID2, and NTRK3, were named AZAAN. Therefore, we evaluated the effect of the predictor-AZAAN on responsive stratification in patients who had received immunotherapy. The results indicated that patients harboring AZAAN(+) received more OS benefits from immunotherapy than those patients harboring AZAAN(−) [AZAAN(+) vs. AZAAN(−): 22 months vs. 10 months, log-rank P value = 0.0006, HR = 0.59]...
DOI:
https://doi.org/10.3389/fimmu.2021.732125
Evidence Level:
Sensitive: C3 – Early Trials
[HGF mutation-Non Small Cell Lung Cancer-Immunotherapy]
Source:
Test:
MSK-IMPACT
Title:
TP53 Mutation Status and Biopsy Lesion Type Determine the Immunotherapeutic Stratification in Non-Small-Cell Lung Cancer
Published date:
09/17/2021
Excerpt:
In the primary sample cohort, the top six upregulated genes (ZPAHPN: ZFHX3, PIK3CA, ARID2, HGF, PDGFRA, and NTRK3) and the bottom downregulated gene (KEAP1) were selected as combined predictors for screening responders from non-responders. The results indicated that patients harboring ZPAHPN(+) received more OS benefits than those harboring ZPAHAN(−) or KEAP1(+)...
DOI:
https://doi.org/10.3389/fimmu.2021.732125
Evidence Level:
Sensitive: C3 – Early Trials
[CDKN2A mutation + TP53 mutation-Non Small Cell Lung Cancer-Immunotherapy]
Source:
Test:
MSK-IMPACT
Title:
TP53 Mutation Status and Biopsy Lesion Type Determine the Immunotherapeutic Stratification in Non-Small-Cell Lung Cancer
Published date:
09/17/2021
Excerpt:
For patients harboring TP53(+), the top five upregulated genes (ZACNN: ZFHX3, ATM, CDKN2A, NOTCH4, and NTRK3) were selected as predictors for screening responders from non-responders. The results indicated that patients harboring ZACNN(+) received more OS benefits from immunotherapy than those harboring ZACNN(−) [ZACNN(+) vs. ZACNN(−) = undefined vs. 8 months, P < 0.0001]...
DOI:
https://doi.org/10.3389/fimmu.2021.732125
Evidence Level:
Sensitive: C3 – Early Trials
[NTRK3 mutation-Non Small Cell Lung Cancer-Immunotherapy]
Source:
Test:
MSK-IMPACT
Title:
TP53 Mutation Status and Biopsy Lesion Type Determine the Immunotherapeutic Stratification in Non-Small-Cell Lung Cancer
Published date:
09/17/2021
Excerpt:
The top five altered genes, namely, ARID1A, ZFHX3, ATM, ARID2, and NTRK3, were named AZAAN. Therefore, we evaluated the effect of the predictor-AZAAN on responsive stratification in patients who had received immunotherapy. The results indicated that patients harboring AZAAN(+) received more OS benefits from immunotherapy than those patients harboring AZAAN(−) [AZAAN(+) vs. AZAAN(−): 22 months vs. 10 months, log-rank P value = 0.0006, HR = 0.59]...
DOI:
https://doi.org/10.3389/fimmu.2021.732125
Evidence Level:
Sensitive: C3 – Early Trials
[CDKN2A mutation-Non Small Cell Lung Cancer-Immunotherapy]
Source:
Test:
MSK-IMPACT
Title:
TP53 Mutation Status and Biopsy Lesion Type Determine the Immunotherapeutic Stratification in Non-Small-Cell Lung Cancer
Published date:
09/17/2021
Excerpt:
In addition, the mutation frequency of multiple genes changed remarkably between the OS >12 months cohort and the OS ≤12 months cohort in the metastatic sample cohort. The top five upregulated genes (AZACN: ARID1A, ZFHX3, ATM, CDKN2A, and NTRK3) and the bottom two downregulated genes (BRAF and PIK3CA) were selected as combined predictors for screening responders from non-responders. The results suggested that patients harboring AZACN(+) received more OS benefits from immunotherapy than those harboring AZACN(−) or harboring BRAF and PIK3CA (+)...
DOI:
https://doi.org/10.3389/fimmu.2021.732125
Evidence Level:
Sensitive: C3 – Early Trials
[ARID2 mutation-Non Small Cell Lung Cancer-Immunotherapy]
Source:
Test:
MSK-IMPACT
Title:
TP53 Mutation Status and Biopsy Lesion Type Determine the Immunotherapeutic Stratification in Non-Small-Cell Lung Cancer
Published date:
09/17/2021
Excerpt:
The top five altered genes, namely, ARID1A, ZFHX3, ATM, ARID2, and NTRK3, were named AZAAN. Therefore, we evaluated the effect of the predictor-AZAAN on responsive stratification in patients who had received immunotherapy. The results indicated that patients harboring AZAAN(+) received more OS benefits from immunotherapy than those patients harboring AZAAN(−) [AZAAN(+) vs. AZAAN(−): 22 months vs. 10 months, log-rank P value = 0.0006, HR = 0.59]...
DOI:
https://doi.org/10.3389/fimmu.2021.732125
Evidence Level:
Sensitive: C3 – Early Trials
[ATM mutation-Non Small Cell Lung Cancer-Immunotherapy]
Source:
Test:
MSK-IMPACT
Title:
TP53 Mutation Status and Biopsy Lesion Type Determine the Immunotherapeutic Stratification in Non-Small-Cell Lung Cancer
Published date:
09/17/2021
Excerpt:
The top five altered genes, namely, ARID1A, ZFHX3, ATM, ARID2, and NTRK3, were named AZAAN. Therefore, we evaluated the effect of the predictor-AZAAN on responsive stratification in patients who had received immunotherapy. The results indicated that patients harboring AZAAN(+) received more OS benefits from immunotherapy than those patients harboring AZAAN(−) [AZAAN(+) vs. AZAAN(−): 22 months vs. 10 months, log-rank P value = 0.0006, HR = 0.59]...
DOI:
https://doi.org/10.3389/fimmu.2021.732125
Evidence Level:
Sensitive: D – Preclinical
[RET fusion-Non Small Cell Lung Cancer-TAS0953/HM06]
Source:
Test:
MSK-IMPACT
Title:
MA13.05 - TA0953/HM06, a Novel RET-specific Inhibitor Effective in Extracranial and CNS Disease Models of NSCLC with RETfusions
Published date:
07/12/2022
Excerpt:
TAS0953/HM06 was as effective as selpercatinib (10-30 mg/kg BID) and pralsetinib (15-30 mg/kg BID) at reducing growth of PDX models. TAS0953/HM06 (50 mg/kg BID) was superior to selpercatinib (10 mg/kg BID, p=0.0002; 25 mg/kg BID, p<0.0001) at inhibiting growth of ECLC5 brain xenograft tumors and increasing survival (selpercatinib 10 mg/kg BID, p=0.0012, selpercatinib 25 mg/kg BID, p=0.001, Log-rank test).Our data show that TAS0953/HM06 is effective at inhibiting growth in vitro and in vivo of preclinical models driven by RET fusions. TAS0953/HM06 was more effective than selpercatinib at decreasing CNS disease and extending survival, at a dose that produced comparable suppression of tumor growth in extracranial disease models. TAS0953/HM06 represents a promising new therapeutic option for patients with RET fusions including those with brain metastasis and those resistant to first-generation selective RET inhibitors.
Evidence Level:
Resistant: D – Preclinical
[TP53 mutation-Urothelial Cancer-erdafitinib]
Source:
Test:
MSK-IMPACT
Title:
3410 / 16 - Identifying potential mechanisms of resistance to erdafitinib (erda) via longitudinal analysis of circulating tumor (ct)-DNA of patients (pts) with advanced/metastatic urothelial cancer (mUC)
Published date:
03/09/2022
Excerpt:
Pts with mUC treated with erda demonstrated on-tx acquisition of ctDNA alts of FGFR2/3 and TP53 and activating alts downstream or parallel to FGFR signaling. Most pts with TP53 alts in baseline ctDNA were refractory to erda. Acquired FGFR2/3 alts on erda may drive resistance through interference with drug-target binding.
