BACKGROUND
Cutaneous melanoma is rare in Patients of Color (POC), and the genomics are not well understood.
OBJECTIVE
Describe MAPK drivers and tumor mutational burden (TMB) of cutaneous and unknown primary (CUP) melanoma in POC and compare them to non-Hispanic White (NHW) patients.
METHODS
We analyzed a retrospective convenience cohort of 676 patients with advanced CUP melanoma undergoing clinically-warranted multigene sequencing with MSK-IMPACT. Self-identified (self-ID) POC were defined as non-White race and/or Hispanic ethnicity; this cohort was also analyzed by genetically inferred ancestry and skin tone using Monk scale.
RESULTS
Self-ID POC (n=35) had frequent BRAF V600E mutations (43%) and, compared to NHW (N=641) patients, more "pan-wildtype" tumors of unknown driver (14% vs 4%, p=0.010). Among self-ID POC, skin tone and inferred ancestry showed moderate overlap, but did not consistently predict genomic features. Median TMB was higher for patients with light (N=185) vs medium/dark (N=8) skin tone (15.8 vs 2.6, p<0.0001).
LIMITATIONS
Skin tone assessments were only available for a subset of patients (N=193). BRAF mutations are underestimated given molecular testing preferentially sent in patients with BRAF-wildtype disease.
CONCLUSION
CUP melanomas in self-ID POC had lower median TMB and were more likely to be pan-wildtype, reflecting differences in pathogenesis. Larger scale studies are needed to validate these findings.
J. Ross, Vanessa R. Weir, Leore Lavin et al.· Journal of American Academy...· 0 citations
PURPOSE
To evaluate the efficacy of ado-trastuzumab emtansine (T-DM1) among patients with advanced/metastatic HER2-amplified solid tumors.
PATIENTS AND METHODS
This was a single-center, non-randomized phase 2 basket trial conducted at Memorial Sloan Kettering Cancer Center. All 95 patients had HER2-amplified metastatic/advanced disease and were enrolled in 1 of 5 cohorts. HER2 amplification was diagnosed either with next-generation sequencing or in-situ hybridization. All patients received intravenous T-DM1 3.6 mg/kg every 21 days. The primary endpoint was overall response rate (ORR). Overall survival (OS), progression-free survival (PFS), duration of response (DOR), and safety were secondary endpoints.
RESULTS
We treated 95 patients, and 22 (23% [95% CI, 16-33%]) had a confirmed response by investigator assessment. The investigator-assessed confirmed ORRs by cohort were: salivary 11/19 (58% [95% CI, 36-77%]); lung 4/23 (17% [95% CI, 7-37%]); colorectal 0/7 (0% [95% CI, 0-35%]); endometrial 5/23 (22% [95% CI, 10-42%]); "other" 2/23 (9% [95% CI, 2-27%]). Median PFS was 3.6 months (95% CI, 2.6-5.4) and ranged from 1.4 months in the "other" cohort to 10.2 months in the salivary cohort. Median OS was 11.9 months (95% CI, 8.4-17.2) and ranged from 7.8 months in the "other" cohort to 29.2 months in the salivary cohort. Median DOR was 13.1 months (95% CI, 7.3-30.5), ranging from 6.4 months in the lung cohort to 18.4 months in the "other" cohort.
CONCLUSIONS
T-DM1 demonstrated heterogenous efficacy among HER2-amplified tumor types, with promising response and outcomes among patients with salivary gland cancer.
J. Ross, W. Wong, Lauren Schoech et al.· Clinical Cancer Research· 0 citations
Small-cell lung cancer (SCLC) is an exceptionally aggressive malignancy: highly proliferative, heterogeneous, and frequently metastatic at diagnosis. Although initially responsive to chemotherapy, such responses are typically transient, and recurrent disease has been largely refractory to standard cytotoxics. The past decade has been notable for major advances in our understanding of SCLC biology, and this preclinical progress is now informing multiple novel therapeutic approaches for this disease. Of particular note, defining cell-surface proteins that are uniquely or differentially expressed in SCLC has led to various targeted therapies showing substantial preliminary evidence of efficacy in patients with SCLC. Approaches in active development include T-cell engagers, antibody-drug conjugates, radioconjugates, and cell therapies, among others. In this Series paper, we summarise current standards of care, recent advances, and highlight emerging approaches showing early promise for better management of SCLC. Together, these advances are providing new hope for patients with what has been a particularly lethal disease.
J. Ross, K. Hockemeyer, E. Redin et al.· The Lancet· 2 citations
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