October 18, 2021

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ESMO 2021: New research progress for Pancreatic cancer treatment

ESMO 2021: New research progress for Pancreatic cancer treatment.

ESMO 2021: New research progress for Pancreatic cancer treatment



ESMO 2021: New research progress for Pancreatic cancer treatment.

The 2021 European Society of Medical Oncology (ESMO) Annual Meeting will be held in the form of an online conference on September 16-21, 2021. At this meeting, the results of a number of important studies on pancreatic cancer were announced. “Tumor Time” organizes related studies for readers.


Application of demethylation drug azacitidine in pancreatic cancer

Evaluation of the efficacy of oral azacitidine (CC-486) ​​in patients with resected pancreatic cancer who have a high risk of recurrence

Background

In only 20% of patients with resectable pancreatic ductal adenocarcinoma (PDA), overall survival (OS) is still very low, because 80% of cases relapse within 2 years after surgery. Epigenetic modulators such as 5-azacitidine (CC-486) ​​may reactivate tumor suppressor genes, delay recurrence and make PDA sensitive to future chemotherapy.

 

Method

This is a CC-486 and Observation (OBS) II in rPDA patients with high-risk characteristics (pN1-2 stage, R1 marginal or CA 19-9 level elevated) and no evidence of disease after standard adjuvant therapy Period research. Patients were randomized to receive oral CC-486 treatment (300 mg per day on days 1-21 of the 28-day cycle) or OBS treatment for up to 12 cycles or until disease recurrence/unacceptable toxicity.

After recurrence, records of off-line treatment, imaging and survival were obtained. The primary endpoint is progression-free survival (PFS), the time from randomization to recurrence (imaging/biopsy confirmation or death). Secondary endpoints include OS and 1ST-line metastatic treatment outcome (PFS and overall response [ORR]).

Results

48 patients (24 in the CC-486 group, 24 in the OBS group) were randomly assigned: median age 65 (range 36-81), 52% male, 73% positive lymph nodes, 50% elevated CA 19-9, 21 % Underwent R1 resection, 65% and 100% received perioperative cRT and chemotherapy, respectively. The median time from surgery to randomization was 10 months (mo) (range 2.9-36.8).

For the CC-486 group, the median duration of treatment was 5.5 months (range 1.3 to 12.8), and 14 of the 6 patients (23%) had treatment-related grade 3 or 4 AEs, resulting in dose reduction and delay. Four patients (17%) discontinued treatment due to AEs. One participant made progress at the time of randomization and was excluded from the PFS analysis. With a median follow-up of 20.5 months (range 0.03-79.7), 38 relapses (72% imaging, 9% clinical).

The median PFS of CC-486 and OBS confirmed cases were 7.8 and 8.9 months, respectively (HR = 1.01, 95% CI: 0.40-2.03). The median OS (2-year OS%) of CC-486 and OBS were 21.9 (46%) and 25.6 months (61%), respectively (HR = 1.01, 95% CI: 0.54-2.26). The meeting will report on the response of CC-486 and OBS groups to chemotherapy in a metastatic setting.

Conclusion

Treatment with CC-486 after adjuvant therapy will not prolong the recurrence time of patients with high-risk rPDA, nor will it improve overall survival.

Clinical trial: NCT01845805.

Heumann T, et al. Oral azacitidine (CC-486) ​​in patients with resected pancreatic adenocarcinoma at high risk for recurrence. Annals of Oncology (2021) 32 (suppl_5): S1084-S1095. 10.1016/annonc/annonc709.


Application of PDGFRα inhibitor olazumab in pancreatic cancer

Results of a randomized, double-blind, placebo-controlled, phase II study of gemcitabine and albumin-bound paclitaxel ± olaratumab in untreated patients with unresectable metastatic pancreatic cancer

Background

Platelet-derived growth factor receptor α (PDGFRα) is overexpressed in pancreatic cancer (PC) and contributes to the activation of pancreatic stellate cells and the formation of the characteristic fibroproliferative matrix. Despite treatments, the prognosis of PC is poor, indicating that the need for new therapies has not been met. This study evaluated the efficacy and safety of olaratumab (OLA).

Mmethod

In this multicenter, randomized (1:1), double-blind, placebo-controlled study, patients with metastatic PC received gemcitabine (1000 mg/m2) and albumin-bound paclitaxel (125 mg/m2) (GA) + OLA (20 mg/kg 1 cycle, followed by 15 mg/kg), or placebo (PBO) on days 1, 8 and 15 of each 28-day cycle until disease progression/intolerance.

The primary endpoint is overall survival (OS). Secondary endpoints include progression-free survival (PFS), tumor response, and safety. The stratified log-rank, stratified Cox regression and Kaplan-Meier estimation methods are used for statistical analysis of time to event results.

Results:

Overall, 159 patients were randomly assigned to OLA+GA (n = 81) or PBO+GA (n = 78). The baseline disease characteristics of the OLA+GA and PBO+GA groups are balanced, and the median age of the population is 66 years. OS (9.1 vs 10.8 months; p = 0.79; HR = 1.05; 95% CI: 0.73–1.53) and PFS (5.6 vs 6.4 months; p = 0.38; HR = 1.19; 95% CI: 0.81-1.76), There are no significant differences. The overall response rate and disease control rate of OLA+GA were (30.5%, 69.5%), the overall response rate and disease control rate of PBO+GA were (33.8%, 77.5%), and the duration of response (5.6 months vs. 5.6) Month; p = 0.57; HR = 1.23; 95% CI: 0.61-2.47). Adverse events during treatment are comparable between treatment groups.

Conclusion

Olaratumab combined with chemotherapy failed to improve OS or PFS in patients with unresectable metastatic PC; safety is controllable.

Clinical trial: NCT03086369.

Gardner F, et al. Results of a randomized, double-blind, placebo-controlled, phase II study of gemcitabine and nab-paclitaxel ± olaratumab in treatment-naïve patients with unresectable metastatic pancreatic cancer. Annals of Oncology (2021) 32 (suppl_5 ): S1084-S1095. 10.1016/annonc/annonc709.


Application of BRAF+MEK inhibitor in non-V600E BRAF solid tumors

Binimetinib and Encorafenib for the treatment of advanced solid tumors with non-V600E BRAF mutations: preliminary results of the investigator-sponsored Phase II BEAVER trial

Background

Recurrent oncogenic non-V600E BRAF mutations can be found in many cancers. Preclinical data indicate that they can be targeted by BRAF+MEK inhibitors. BEAVER is a study initiated by investigators to test the safety and effectiveness of Binimetinib and encorafenib (B+E) in patients with non-V600E BRAF mutations.

Method

The key eligibility criteria are: patients with advanced solid tumors with BRAF non-V600E activating (grade 1 and 2) or inhibitory (grade 3) mutations and no previous BRAF/MEKi treatment. Patients received binimetinib (45 mg PO BID) and encorafenib (450 mg PO per day) on a 28-day cycle until intolerable toxicity or progression.

The main goal is the objective response rate (ORR) based on RECIST 1.1. In this Simon Phase 2 trial, ≥ 1 of 7 patients must respond before starting Phase 2 (26 total). Secondary goals include: security, DCR and PFS.

Results

From June 2019 to April 2021, recruit 10 people. 10 items can be evaluated for safety and 9 items can be evaluated for effectiveness. The tumor types were: melanoma and colon (n = 2 each), gallbladder, lung, breast, ampulla, pancreas, and uterus (n = 1 each). The median age is 61 years (range 40-72). 1 person belongs to category 1, 4 people belong to category 2, and 5 people belong to category 3 non-V600E BRAF mutations.

Common treatment-related adverse events are mostly grade ≤ 2, including: blurred vision (70%), fatigue (60%), and nausea (50%). 5/10 patients (50%) need to reduce the dose due to: blurred vision (20%), central serous retinopathy, malaise, increased lipase and nausea (10% each). With the interruption or reduction of the dose, the ocular toxicity is reversible.

Drug-related grade 3 AEs occur in 2/10 patients and include: malaise, confusion, fatigue, and increased lipase (10% each). The ORR was 22% (2/9), which was confirmed as PR in patients with ampullary carcinoma (BRAF D594 G, grade 3) who had been treated continuously for more than 5.4 months, and PR was not confirmed in patients with melanoma (BRAF G469S, grade 2) , Treatment for 6.5 months. One patient with gallbladder cancer (BRAF D594N, grade 3) had SD and was treated for 4.4 months; 6 patients had PD as the best response.

Conclusion

Preliminary data confirmed the safety of B+E and demonstrated evidence of anti-tumor activity in advanced cancer patients with non-V600E BRAF mutations. Registration for the BEAVER trial is in progress.

Clinical trial: NCT03839342.

Rose A, et al. Binimetinib and encorafenib for the treatment of advanced solid tumors with non-V600E BRAF mutations (mts): Preliminary results of the investigator initiated phase II BEAVER trial. Annals of Oncology (2021) 32 (suppl_5): S583- S620. 10.1016/annonc/annonc699.


Neoadjuvant chemotherapy combined with radiotherapy for advanced pancreatic cancer

In the treatment of borderline resectable and locally advanced pancreatic cancer, is it worth adding a systematic review of concurrent radiotherapy or radiotherapy on the basis of neoadjuvant chemotherapy

Background

There is a lack of strong Level 1 evidence regarding the role of concurrent radiotherapy (CCRT) or radiotherapy (RT) after neoadjuvant chemotherapy (NACT) in borderline resectable (BR) and locally advanced (LA) pancreatic ductal adenocarcinoma (PDA). This systematic review aims to investigate whether CCRT or RT, when added to the NACT regimen, can produce any significant prognosis for patients with BR and LA PDA.

Method

We systematically searched PubMed, Medline, Embase, and Cochrane systematic review databases. For articles published in English between 2005 and 2020, eligible studies that meet our inclusion criteria were independently screened by two authors.

Evaluate the design and quality of the study, and perform qualitative data analysis to understand the treatment’s resection rate, R0 resection, pathological response, imaging response, progression-free survival, overall survival, local control, postoperative morbidity and mortality Impact.

Conclusion

When NACT is added to CCRT or RT, the local control and pathological response of BR and LA PDA can be improved. The role of modern radiotherapy in improving resectability, progression-free survival, overall survival, and reducing treatment morbidity and mortality requires further research.

Saha A, et al. Is it worth adding concurrent chemo-radiotherapy or radiotherapy on the top of neoadjuvant chemotherapy in the management of borderline resectable and locally advanced pancreatic adenocarcinoma? A systematic review. Annals of Oncology (2021) 32 (suppl_5): S1084 -S1095. 10.1016/annonc/annonc709.

ESMO 2021: New research progress for Pancreatic cancer treatment.

(source:internet, reference only)


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