"The Lancet" sub-issue: Not better than chemotherapy, ADC drugs challenge malignant pleural mesothelioma and get negative results; T-DXd is planned to be included in breakthrough therapy in China!

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Lancet Oncol: ADC drug Anetumab ravtansine in the treatment of recurrent, mesothelin-positive malignant pleural mesothelioma or no better than chemotherapy 2.
JCO: through MAPK pathway mutation Status guides pediatric oncology treatment, what are the outcomes? Another attempt at precision medicine! 3.
Frontiers: ADC drug DS-8201 is planned to be included in breakthrough therapy varieties in China There are few second-line treatment options for recurrent, mesothelin-positive malignant pleural mesothelioma or for malignant pleural mesothelioma that is not superior to chemotherapy
.

A study comparing the antibody-drug conjugate (ADC) Anetumab ravtansine with vinorelbine in patients with recurrent mesothelin-positive malignant pleural mesothelioma was published in The Lancet Oncology
.

The results show that Anetumab ravtansine has a manageable safety profile, but may not be superior to vinorelbine, and further studies are needed to determine the treatment options for recurrent mesothelin-expressing malignant pleural mesothelioma
.

Screenshot from journal website This randomized, open-label, phase II study at 76 hospitals in 14 countries enrolled adults (age ≥18 years) with unresectable locally advanced or metastatic malignant pleural mesothelioma, Eastern United States Patients with a Cooperative Oncology Group (ECOG) performance status score of 0-1 and who had disease progression after first-line platinum-based + pemetrexed chemotherapy (with or without bevacizumab)
.

Patients were tested for mesothelin overexpression (defined as mesothelin membrane staining intensity of 2+ or 3+ in at least 30% of viable tumor cells by immunohistochemistry) and were randomly assigned (2:1) to receive intravenous injections Anetumab ravtansine (6.
5 mg/kg on day 1 of every 21-day cycle) or intravenous vinorelbine (30 mg/m2 weekly) until disease progression, intolerable toxicity, or death
.

The primary endpoint was progression-free survival (PFS) according to blinded central radiology review, as assessed in the intention-to-treat (ITT) population, and safety was assessed in all patients
.

A total of 248 mesothelin-overexpressing patients were randomly assigned to two treatment arms (166 patients received Anetumab ravtansine and 82 patients received vinorelbine)
.

The median PFS in the two groups was 4.
3 months and 4.
5 months, respectively (HR 1.
22; 95% CI 0.
85–1.
74; log-rank p=0.
86)
.

The most common grade 3 or more serious adverse events were neutropenia (1% vs 39%), pneumonia (4% vs 7%), decreased neutrophil count (1% vs 17%) and respiratory Difficulty (6% vs 4%)
.

Serious drug-related adverse events occurred in 12 (7%) patients receiving Anetumab ravtansine and 11 (15%) patients receiving vinorelbine
.

Anetumab ravtansine resulted in 10 (6%) treatment-induced deaths: pneumonia (3, 2%), dyspnea (2, 1%), sepsis (2, 1%]), atrial fibrillation (1, 1 %), physical deterioration (1, 1%), liver failure (1 case, 1%), mesothelioma (1 case, 1%), and renal failure (1 case, 1%)
.

One (1%) treatment-induced death (pneumonia) occurred in the vinorelbine group
.

02JCO: MAPK pathway mutation status to guide pediatric cancer treatment, what are the results? Another attempt at precision medicine! Results of a phase II NCI-COG Pediatric MATCH study to test the use of precision medicine in childhood cancer were published in the Journal of Clinical Oncology
.

In this study, patients with activating mutations or fusions that drive the mitogen-activated protein kinase (MAPK) pathway were treated with the MEK inhibitor Selumetinib
.

The results showed that although MEK inhibitors have shown some efficacy in some pediatric tumors, selumetinib has limited efficacy in refractory tumors with MAPK alterations, which may indicate that detection of frontal pathway mutation status alone is not sufficient to predict Selumetinib alone.
Efficacy of drug therapy for childhood cancer
.

In this study, patients aged 1-21 with relapsed or refractory solid tumors, lymphomas, and histiocytic diseases were treated with the MEK inhibitor Selumetinib (twice a day) based on the type of genetic mutation detected.
times for 28 days) until disease progression or intolerable toxicity
.

The primary endpoint was objective response rate (ORR); secondary endpoints included freedom from PFS and tolerability
.

RESULTS: Among 20 patients (median age 14 years), high-grade gliomas (HGG; n=7) and rhabdomyosarcomas (n=7) were the most common
.

21 actionable mutations detected: hotspot mutations in KRAS (n=8), NRAS (n=3) and HRAS (n=1), inactivation in NF1 (n=7) and BRAFV600E (n=2) mutation
.

However, no objective response was observed in any of these patients
.

Three patients responded best to stable disease, including two with HGG (NF1 mutation, 6 cycles; KRAS mutation, 12 cycles)
.

The 6-month PFS rate was 15% (95% CI 4%-34%)
.

Five patients (25%) experienced adverse events of grade 3 or higher that were possibly related to selumetinib
.

03 Frontier: ADC drug DS-8201a to be included in breakthrough therapy in China 8201 is intended to be included as a breakthrough therapy for the treatment of adult patients with unresectable or metastatic HER2-positive breast cancer who have received one or more prior anti-HER2 drugs
.

According to public information, DS-8201 is a HER2-targeting ADC jointly developed by AstraZeneca and Daiichi Sankyo, which has been approved for marketing overseas
.

The drug's marketing application in China has also been accepted by the CDE not long ago
.

04New drug: For the first time in 30 years, CAR-T therapy surpassed standard therapy, and CAR-T therapy was approved by the FDA as a second-line treatment for large B-cell lymphoma.
Today, the U.
S.
Food and Drug Administration (FDA) approved the CD19-targeted CAR-T developed by Kite Pharma, a subsidiary of Gilead Sciences.
The therapy Yescarta (axicabtagene ciloleucel) has been expanded for second-line treatment of adult patients with large B-cell lymphoma (LBCL)
.

These patients developed resistance after receiving first-line chemoimmunotherapy, or relapsed within 12 months of receiving first-line therapy, and are not suitable for the treatment of patients with primary central nervous system lymphoma
.

Kite Pharma noted that the therapy is the first approved therapy in nearly 30 years to improve patient outcomes compared to standard therapy
.

This approval is based on the randomized, open-label clinical trial ZUMA-7 study
.

The results of the study showed that 359 patients were randomized to receive a single dose of Yescarta or standard second-line therapy, and patients in the Yescarta group had significantly longer event-free survival (EFS) (HR=0.
40, 95% CI 0.
31, 0.
51; p<0.
0001)
.

The estimated EFS was 8.
3 months in the Yescarta group and 2.
0 months in the standard-care group
.

The ORR assessed by an independent review committee in the Yescarta arm was 83%, significantly better than the 50% in the control arm
.

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Kindler HL, et al.
Lancet Oncol.
2022 Apr;23(4):540-552.
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Eckstein OS, et al.
J Clin Oncol.
2022 Apr 1:JCO2102840.
doi: 10.
1200/JCO.
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https:/ /ascopubs.
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https://mp.
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https://mp.
weixin.
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com/s /dMRBBc5nOhsoOLIsB5P1eA