Amivantamab plus chemotherapy with and without lazertinib in EGFR-mutant advanced NSCLC after disease progression on osimertinib: primary results from the phase III MARIPOSA-2 study.

BACKGROUND: Amivantamab plus carboplatin-pemetrexed (chemotherapy) with and without lazertinib demonstrated antitumor activity in patients with refractory epidermal growth factor receptor (EGFR)-mutated advanced non-small-cell lung cancer (NSCLC) in phase I studies. These combinations were evaluated in a global phase III trial. PATIENTS AND METHODS: A total of 657 patients with EGFR-mutated (exon 19 deletions or L858R) locally advanced or metastatic NSCLC after disease progression on osimertinib were randomized 2 : 2 : 1 to receive amivantamab-lazertinib-chemotherapy, chemotherapy, or amivantamab-chemotherapy. The dual primary endpoints were progression-free survival (PFS) of amivantamab-chemotherapy and amivantamab-lazertinib-chemotherapy versus chemotherapy. During the study, hematologic toxicities observed in the amivantamab-lazertinib-chemotherapy arm necessitated a regimen change to start lazertinib after carboplatin completion. RESULTS: All baseline characteristics were well balanced across the three arms, including by history of brain metastases and prior brain radiation. PFS was significantly longer for amivantamab-chemotherapy and amivantamab-lazertinib-chemotherapy versus chemotherapy [hazard ratio (HR) for disease progression or death 0.48 and 0.44, respectively; P < 0.001 for both; median of 6.3 and 8.3 versus 4.2 months, respectively]. Consistent PFS results were seen by investigator assessment (HR for disease progression or death 0.41 and 0.38 for amivantamab-chemotherapy and amivantamab-lazertinib-chemotherapy, respectively; P < 0.001 for both; median of 8.2 and 8.3 versus 4.2 months, respectively). Objective response rate was significantly higher for amivantamab-chemotherapy and amivantamab-lazertinib-chemotherapy versus chemotherapy (64% and 63% versus 36%, respectively; P < 0.001 for both). Median intracranial PFS was 12.5 and 12.8 versus 8.3 months for amivantamab-chemotherapy and amivantamab-lazertinib-chemotherapy versus chemotherapy (HR for intracranial disease progression or death 0.55 and 0.58, respectively). Predominant adverse events (AEs) in the amivantamab-containing regimens were hematologic, EGFR-, and MET-related toxicities. Amivantamab-chemotherapy had lower rates of hematologic AEs than amivantamab-lazertinib-chemotherapy. CONCLUSIONS: Amivantamab-chemotherapy and amivantamab-lazertinib-chemotherapy improved PFS and intracranial PFS versus chemotherapy in a population with limited options after disease progression on osimertinib. Longer follow-up is needed for the modified amivantamab-lazertinib-chemotherapy regimen.

Associations of tissue tumor mutational burden and mutational status with clinical outcomes in KEYNOTE-042: pembrolizumab versus chemotherapy for advanced PD-L1-positive NSCLC.

BACKGROUND: We evaluated whether tissue tumor mutational burden (tTMB) and STK11, KEAP1, and KRAS mutations have clinical utility as biomarkers for pembrolizumab monotherapy versus platinum-based chemotherapy in patients with programmed death ligand 1 (PD-L1)-positive (tumor proportion score ≥1%) advanced/metastatic non-small-cell lung cancer (NSCLC) without EGFR/ALK alterations in the phase III KEYNOTE-042 trial. PATIENTS AND METHODS: This retrospective exploratory analysis assessed prevalence of tTMB and STK11, KEAP1, and KRAS mutations determined by whole-exome sequencing of tumor tissue and matched normal DNA and their associations with outcomes in KEYNOTE-042. Clinical utility of tTMB was assessed using a prespecified cut point of 175 mutations/exome. RESULTS: Of 793 patients, 345 (43.5%) had tTMB ≥175 mutations/exome and 448 (56.5%) had tTMB <175 mutations/exome. No association was observed between PD-L1 expression and tTMB. Continuous tTMB score was associated with improved overall survival (OS) and progression-free survival among patients receiving pembrolizumab (Wald test, one-sided P < 0.001) but not those receiving chemotherapy (Wald test, two-sided P > 0.05). tTMB ≥175 mutations/exome was associated with improved outcomes for pembrolizumab versus chemotherapy, whereas tTMB <175 mutations/exome was not {OS: hazard ratio, 0.62 [95% confidence interval (CI) 0.48-0.80] and 1.09 (95% CI 0.88-1.36); progression-free survival: 0.75 (0.59-0.95) and 1.27 (1.04-1.55), respectively}. Improved OS [hazard ratio (95% CI)] for pembrolizumab versus chemotherapy was observed regardless of STK11 [STK11 mutant (n = 33): 0.37 (0.16-0.86), STK11 wild-type (n = 396): 0.83 (0.65-1.05)]; KEAP1 [KEAP1 mutant (n = 64): 0.75 (0.42-1.35), KEAP1 wild-type (n = 365): 0.78 (0.61-0.99)], or KRAS [KRAS mutant (n = 69): 0.42 (0.22-0.81); KRAS wild-type (n = 232): 0.86 (0.63-1.18)] mutation status. CONCLUSION: tTMB with a cut point of ≥175 mutations/exome is a potential predictive biomarker for pembrolizumab monotherapy for advanced/metastatic PD-L1 tumor proportion score ≥1% NSCLC. Pembrolizumab is a standard first-line treatment in this setting regardless of STK11, KEAP1, or KRAS mutation status.

Diagnostic value of plasma expression of microRNAs complementary to Drosha and Dicer in lung cancer patients.

OBJECTIVE: Lung cancer (LC) is diagnosed mostly in advanced, non-operable stage, with poor prognosis. The analysis of microRNAs may be a useful tool for early and non-invasive detection of cancer. Dicer and Drosha are enzymes with an essential role for microRNA biogenesis. The aim of our study was to analyze the expression of miRNA-27a-3p, miRNA-31, miRNA-182, miRNA-195 with the ability to reciprocal regulation of Dicer and Drosha expression in lung cancer patients. PATIENTS AND METHODS: The relative expression of microRNAs was detected by qPCR in plasma of 160 LC patients. The U-Mann Whitney test was used to compare the relative expression between particular groups of lung cancer patients and healthy individuals. The diagnostic value of microRNAs examination was analyzed using a receiver operating curve. RESULTS: We demonstrated that the plasma levels of miRNA-27, miRNA-31 and miRNA-182 were significantly higher and miRNA-195 significantly lower in the whole group of LC patients and in patients with early stages of NSCLC, in comparison with healthy donors. ROC analysis showed that four studied microRNAs have a potential diagnostic value for early stages of NSCLC with AUC=0.95 for miRNA-27a (94% sensitivity and 81% specificity, p=0.0001), 0.71 for miRNA-31 (73% sensitivity and 61% specificity, p=0.001) 0.77 for miRNA-182 (70% sensitivity and 79% specificity, p=0.0001) and 0.82 for miRNA-195 (74% sensitivity and 80% specificity, p=0.0001). CONCLUSIONS: We have proved that the expression of miRNA-27a-3p, miRNA-31, miRNA-182, and miRNA-195 in patients with LC is different from the expression of these molecules in healthy people. The examination of these microRNAs in plasma could be used in non-invasive lung cancer diagnosis.

[Anthracycline antibiotics in treatment of neoplasms]. / Antybiotyki antracyklinowe w leczeniu nowotworów.

The reviews is a description of one group of cytostatics, namely anthracyclines. It presents a short characteristic of all anthracyclines applied as chemotherapeutic drugs in oncology since many years, and also those which are in the phase of clinical trials. The authors have focused on pharmacodynamics, mechanisms of action, and main side effects, and also the therapeutic use of the particular drugs.

Pretreatment values of serum CA 15-3 antigen related to prognostic factors in breast cancer patients.

In the present study results of serum CA 15-3 immunoassay obtained at diagnosis in 231 breast cancer women (average age: 54.6, range: 27-87 years) were correlated with prognostic factors of the disease; the cut-off level was established at 30.0 U/ ml. As a result, elevated mean values of serum CA 15-3 as well as positivity rates of the test were significantly associated with more advanced stage of breast cancer, presence of distant metastases, involvement of four and more axillary lymph nodes, high BLOOM and RICHARDSON grade [3], low contents of estrogen (ER) and progesterone (PgR) receptors. Although serum CA 15-3 concentrations should be paralleled the increasing tumor size, the difference being significant only for the proportion of positive results. Our findings suggest that pretreatment levels of CA 15-3 antigen represent the breast cancer extent and reflect the cell differentiation and aggressiveness of the tumor. We conclude that pretreatment concentrations of CA 15-3 antigen may be useful as a prognostic factor in breast cancer patients.

[Level of CA 15-3 antigen--a prognostic factor in patients with breast cancer?]. / Stezenie antygenu CA 15-3--czynnik rokowniczy u chorych na raka sutka?

Serum CA 15-3 concentrations were determined using sandwich enzyme immunoassay in 430 women: 214 breast cancer patients prior to any therapy, 161 patients with benign breast diseases, and 55 healthy controls; the cut-off limit was established at 30.0 U/ml. In breast cancer patients, CA 15-3 levels positively correlated with negative prognostic factors: higher tumor size (p < 0.001), positive axillary lymph nodes (p < 0.02), high histological grade (p < 0.01), low contents of estrogen (p < 0.05) and progesterone (p < 0.006) receptors. However serum CA 15-3 values raised in parallel with clinical stage of breast cancer, the difference was not significant. The overall diagnostic sensitivity and specificity of the test were 24.3% and 94.9%, respectively. The mean serum CA 15-3 values and the percentage of positive results in breast cancer patients were significantly higher as compared to benign breast diseases group (27.52 +/- 27.01 vs. 16.75 +/- 8.43, p < 0.001; 24.3% vs. 5.6%, p < 0.001, respectively) as well as to healthy controls (27.52 27.01 vs. 13.37 +/- 6.51, p < 0.001; 24.3% vs. 3.6%, p < 0.01, respectively). The sensitivity of the CA 15-3 test is low and thus not suitable for the differential diagnosis of breast lumps. Our data suggest potential prognostic value of pretreatment CA 15-3 assays in breast cancer patients.