We report 2 patients with BRAF V600 mutant melanoma who were previously treated with anti-PD-1±anti-LAG-3 antibodies and were switched to BRAF/MEK-inhibitors because of progressive disease.
Combined MYC family amplifications and P53 pathway defects commonly emerged at relapse, and all patients in this group died of rapidly progressive disease postrelapse.
A total of 52 patients were evaluable.H2T level was significantly higher in responders (median 93.49 in partial response, 47.66 in stable disease, and 17.27 in progressive disease; p = 0.020).
Immunohistochemistry analysis revealed that metastatic neck tumor with the clinical complete response to nivolumab showed higher PD-L1 expression with higher CD8+ TIL density, while primary lesion with progressive disease showed lower PD-L1 expression with lower CD8+ TIL density.
In two patients with K-RAS mutations pretreatment, posttreatment plasmas were evaluated: a patient with clinical progressive disease retained the mutant DNA, while in a patient with a complete response (CR), the K-RAS mutation was no longer detectable.
In a subset of patients, we further showed that reappearance of EGFR mutations could be detected in plasma up to 5 months ahead of progressive disease (PD), suggesting an early detection of drug resistance.
A progressive disease after chemotherapy completion was noted in 35.6% of the patients (26 out of 73); in 69.2%, a mutated p53 and in 30.8%, a wild-type p53 was found.
The absence of statistically significant correlations between p53 gene mutation and progressive disease, however, does not deny its putative relevance in early phases of tumor development.
Patients with complete or partial remission were compared with those with stable or progressive disease with respect to TP53 genotype and overall survival.
Multivariate analysis demonstrated that anthracycline plus taxane chemotherapy (P = 0.006), NG3 (P = 0.006), HR-negativity (P = 0.013), and HER2-positivity (P = 0.010) were significant predictors of pCR, and T3-4 (P = 0.002) and NG3 (P = 0.010) were significant predictors of PD.
Continuation of EGFR TKI beyond progressive disease is confined to patients in asymptomatic stage when the EGFR addiction is still preserved in some subclones.
The clinical response to EGFR TKIs was reassessed for all patients as follows: 16 of 73 patients had a partial response (21.9%), 12 patients had stable disease (16.5%), and 45 patients had progressive disease (61.6%).
A female patient with oestrogen receptor-positive and human epidermal growth factor receptor 2 (HER2)-positive invasive lobular breast cancer presented with progressive disease on CT scan.
Adult patients (age > or = 18 years), with non squamous EGFR mutation, treated with first line palliative therapy, with non progressive disease post 4-6 cycles of pemetrexed-carboplatin were randomized.
Six had V600E-positive tumours (n=4 had PD; n=1 had SD; n=1 unevaluable for response), and 11 had tumours containing wild-type BRAF (n=9 PD; n=1 SD; n=1 unevaluable for response).
Of 24 patients with actionable mutations, five were given genotype-matched drugs corresponding to actionable mutations: everolimus to PIK3CA mutation in parotid carcinosarcoma (partial response) and tracheal squamous cell carcinoma (stable disease; 21% reduction), sorafenib to PDGFRA mutation in auditory canal adenocarcinoma (partial response), sorafenib to BRAF mutation in microcytic adnexal carcinoma (progressive disease), and afatinib to ERBB2 mutation in esophageal adenocarcinoma (progressive disease).
Patients who achieved stable disease (SD) or progressive disease (PD) received EC (epirubicin and cyclophosphamide) or HT (trastuzumab and paclitaxel) according to their HER2 status.The primary end point was the pCR rate.