FDA approves pembrolizumab as the first-line treatment indication for esophageal cancer; China's first RET inhibitor, pratinib, is approved|Tumor News

*Only for medical professionals to read for reference, 1 minute a day, to give you professional "talking information" in the tumor circle! (If you need the original text of the literature, you can add the editor's WeChat yxj_oncology to obtain) Key points: JCO: Tipifarnib has a significant effect on HRAS-mutated head and neck squamous cell carcinoma GUT: endoscopic radiofrequency ablation ± endoscopic resection has significant long-term effect on esophageal Barrett disease Neoadjuvant therapy with nizumab combined with high-dose interferon Alfa-2b is effective for resectable locally advanced melanoma.
New drug: FDA approves pembrolizumab for first-line treatment of esophageal cancer.
New drug: China’s first RET inhibitor pratinib was awarded Batch 01JCO: Tipifarnib has a significant effect on HRAS-mutated head and neck squamous cell carcinoma.
On March 22, 2021, the Journal of Clinical Oncology published a study online showing that Tipifarnib is effective for recurrent and/or metastatic (R/M) heads with HRAS mutations.
Patients with cervical squamous cell carcinoma (HNSCC) have a significant effect.

4%-8% of R/MHNSCC patients carry HRAS (mHRAS) proto-oncogene mutations.

Tipifarnib is a farnesyltransferase inhibitor that can disrupt the function of HRA.

This study aims to evaluate the efficacy of Tipifarnib in patients with R/M mHRAS-HNSCC.

The study included 22 R/M HNSCC patients with mHRAS allele mutation frequency (VAF) ≥ 20% (high VAF).

The primary endpoint of the study is the objective response rate (ORR), and the secondary endpoints include safety and tolerability.

Subjects took Tipifarnib 600 or 900 mg orally twice daily on days 1-7 and 15-21 of the 28-day treatment cycle.

The results show that 20 patients can finally be evaluated for efficacy, and the ORR of patients with high VAF-HNSCC is 55%.

The median progression-free survival (PFS) of Tipifarnib treatment was 5.
6 months, and the median overall survival (OS) was 15.
4 months.

The most common treatment-related adverse events were anemia (37%) and lymphopenia (13%).

02GUT: Endoscopic radiofrequency ablation±endoscopic resection has a significant long-term effect on Barrett disease of the esophagus.
On March 22, 2021, GUT published a study online showing the results of endoscopic radiofrequency ablation (RFA)±endoscopic resection ( ER) has a significant long-term effect on Barrett disease of the esophagus.

Screenshot of the cover of the paper.
Barrett's disease refers to the metaplasia of the esophageal epithelium, that is, the normal squamous epithelium of the lower esophagus is covered by columnar epithelium, which is a precancerous lesion of esophageal cancer.

RFA±ER is the preferred treatment for Barrett's disease.

The researchers analyzed the short-term and long-term results of 1384 patients who received uniform treatment and follow-up in the Netherlands from 2008 to 2018.

The results showed that after ER (62% of cases; 43% of low-risk cancers) and median 1 full circumference and 2 focal radiofrequency ablation, 94% (1270/1348) of patients reached Barrett's esophagus complete Eradication (CE-BE).

The incidence of adverse events was 21% (268/1386), and the most common was esophageal stenosis (15%).

By analyzing the long-term prognostic data of 1154 patients with CE-BE, it was found that during a median follow-up of 43 months and 4 endoscopy, 38 patients had recurrence (3%, the annual risk of recurrence 1%), and the recurrence patients were all The lesion is visible under the endoscope.

A random biopsy of the normal appearance of the cardia of the patient revealed that the intestinal metaplasia rate (IM) was 14%, and no tumor was found.

Further follow-up found that only 33% of patients found IM in the cardia, but did not progress to tumor.

Frequent follow-up in the first year has nothing to do with the risk of recurrence.

RFA±ER can effectively eradicate Barrett-related tumors, and the recurrence rate of abnormal hyperplasia is low.

Research data supports a more relaxed follow-up interval for Barrett’s disease and emphasizes careful endoscopy.
However, the value of random biopsy of cardia epithelium remains to be discussed.

03CCR: Pembrolizumab combined with high-dose interferon Alfa-2b neoadjuvant therapy is effective for resectable locally advanced melanoma.
On March 22, 2021, Clinical Cancer Reseach published a study online, the results showed that for resectable locally advanced melanoma For patients with melanoma, pembrolizumab combined with high-dose interferon (HDI) Alfa-2b neoadjuvant therapy is effective.

Screenshot of the cover of the paper.
Neoadjuvant immunotherapy can improve the clinical efficacy of locally advanced operable melanoma, and can quickly evaluate clinical and pathological responses.

This study aims to explore the efficacy of neoadjuvant pembrolizumab combined with HDIAlfa-2b in the treatment of resectable locally advanced melanoma.

The enrolled patients also received intravenous infusion of 200 mg pembrolizumab and HDI Alfa-2b 20MU/m2/day every three weeks, five days a week for four weeks; then they received 10MU/m2/day HDI Alfa-2b Subcutaneous injection, three days a week, for two weeks.

Then the patient underwent surgical treatment and received adjuvant combined immunotherapy for 1 year after the operation.

The primary endpoint of the study is the safety of the combination medication.

Secondary endpoints include overall response rate (ORR), pathological complete response (pCR) rate, recurrence-free survival (RFS) rate, and OS.

The results showed that the efficacy can be evaluated in 30 patients.
As of October 2, 2019, the median OS was 37.
87 months.

The median OS and RFS were not reached.

The imaging ORR was 73.
3%, and the pCR rate was 43%.

None of the patients who achieved pCR recurred.

The withdrawal rates of HDI and Pembrolizumab were 73% and 43%, respectively.

The analysis showed that the expression of PD-1/PD-L1 and HLA-DR in the tumor was correlated with pCR (p=0.
002 and p=0.
008).

04 New drug: FDA approved Pembrolizumab as the first-line treatment indication for esophageal cancer.
On March 23, local time, Merck (MSD) announced that the US Food and Drug Administration (FDA) has approved the company's blockbuster PD-1 single Anti-pembrolizumab combined with platinum-containing chemotherapy is the first-line treatment for locally advanced or metastatic esophageal cancer or gastroesophageal junction cancer (GEJ) that is unresectable or not suitable for radical radiotherapy and chemotherapy, regardless of PD-L1 expression.

This is the first anti-PD-1 immune combination therapy approved by the FDA for the first-line treatment of the entire population of esophageal cancer.
Since then, immunotherapy has officially rewritten the first-line treatment pattern of esophageal cancer, and also represents a major first-line treatment of esophageal cancer in the past 30 years.
breakthrough.

05 New drug: China's first RET inhibitor pratinib was approved.
The latest announcement of the results of the drug registration progress of China National Medical Products Administration (NMPA), and the new drug listing application for RET inhibitor pralsetinib declared by CStone Pharmaceuticals The review and approval status has been updated to "Approval completed-pending certification", and the approval number is: National Medicine Standard HJ20210018, which means that the drug has been officially approved.

Public information shows that the indication for this application of the drug is locally advanced or metastatic non-small cell lung cancer (NSCLC) adult patients who have previously received platinum-containing chemotherapy and RET gene fusion-positive.

References: [1].
Ho AL, Brana I, Haddad R, et al.
Tipifarnib in Head and Neck Squamous Cell Carcinoma With HRAS Mutations.
J Clin Oncol.
2021 Mar 22:JCO2002903.
doi: 10.
1200/JCO.
20.
02903.
Epub ahead of print.
PMID: 33750196.
[2].
van Munster S, Nieuwenhuis E, Weusten BLAM, et al.
Long-term outcomes after endoscopic treatment for Barrett's neoplasia with radiofrequency ablation ± endoscopic resection: results from the national Dutch database in a 10-year period.
Gut.
2021 Mar 22:gutjnl-2020-322615.
doi: 10.
1136/gutjnl-2020-322615.
Epub ahead of print.
PMID: 33753417.
[3].
NajjarYG, McCurryD, LinH, et al.
Neoadjuvant Pembrolizumab and High Dose Interferon Alfa-2b in Resectable Regionally Advanced Melanoma.
Clin Cancer Res.
2021 Mar 22:clincanres.
4301.
2020.
doi: 10.
1158/1078-0432.
CCR-20-4301.
Epub ahead of print.
PMID: 33753453.
[ 4].