Featured video: Phase III Keynote-177 trial comparing pembrolizumab to standard therapy as first-line treatment for select patients with advanced colorectal cancer.
The first phase 3 study of pembrolizumab versus standard-of-care (i.e. chemotherapy + bevacizumab or cetuximab) demonstrated superiority for first-line pembrolizumab in patients with high microsatellite instability (MSI-H) metastatic colorectal cancer (mCRC), reported Prof. Thierry André (St Antoine Hospital, France) [1].
About 5% of all mCRC is characterised by MSI-H, often linked with germline mutations in Lynch syndrome. Mismatch repair status and MSI-H predict clinical benefit of immune checkpoint blockade with pembrolizumab as first-line therapy for MSI-H mCRC and has been FDA approved for adults and children with metastatic tumours with MSI, regardless of the tumour type. Previously, KEYNOTE-164 evaluated the anti-tumour activity of pembrolizumab in previously treated, metastatic, microsatellite instability-high/mismatch repair-deficient (MSI-H/dMMR) CRC [2]. In the current study, treatment-naïve MSI-H patients were treated with first-line pembrolizumab.
KEYNOTE-177 studied 307 stage IV, treatment-naïve CRC patients with confirmed MSI-H/dMMR with good performance status. Patients were randomised to either pembrolizumab (n=153; 200 mg every 3 weeks for up to 35 cycles) or investigator-choice chemotherapy (n=154; mostly mFOLFOX6- or FOLFIRI-based, plus bevacizumab or cetuximab). There was an optional crossover to the pembrolizumab regimen for patients with centrally verified disease progression by RECIST v1.1. The dual primary endpoints were progression-free survival (PFS) per RECIST v1.1 by blinded independent central review (BICR) and overall survival. Secondary endpoints were overall response rate and safety. Tumour response was assessed at week 9 and every 9 weeks thereafter per RECIST v1.1 by BICR.
With a median follow-up of 32.4 months (range 24.0-48.3), pembrolizumab was superior to chemotherapy in terms of PFS: 16.5 months in the pembrolizumab group versus 8.2 months in the chemotherapy control arm (HR 0.60; 95% CI 0.45-0.80; P=0.0002, see Figure). Overall survival data are still immature. The overall response rate was 43.8% in the pembrolizumab arm as compared with 33.1% in the chemotherapy control arm (P=0.0275). The medial duration of response was not reached in the pembrolizumab arm but was 10.6 months in the chemotherapy arm.
Treatment-related adverse events of grade 3 or higher were reported in 22% of the patients in the pembrolizumab arm, as opposed to 66% of the patients in the chemotherapy arm. No new toxicities with pembrolizumab were observed.
In short, pembrolizumab provided a clinically meaningful and statistically significant improvement in PFS versus chemotherapy in patients with MSI-H mCRC. Responses were also more durable with pembrolizumab. Furthermore, there was an improved safety profile with pembrolizumab versus chemotherapy. Prof. André concluded that “pembrolizumab should be considered a new standard-of-care as first-line therapy in patients with MSI-H mCRC.”
Figure. Anti-tumour activity of pembrolizumab versus standard-of-care (chemo) in patients with high microsatellite instability (MSI-H) metastatic colorectal cancer (mCRC) [1]
- André T, et al. ASCO Virtual Meeting, 29-31 May 2020, Abstract LBA4.
- Le DT, et al. J Clin Oncol. 2020;38(1):11‐19.
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Table of Contents: ASCO 2020
Featured articles
COVID-19 & Telemedicine
COVID-19 and Cancer Consortium Registry: initial results
Oncology hospital-at-home model reduces hospitalizations, emergency department visits, and costs
Nurse-led telephone triage system reduces hospitalizations, helps patients manage symptoms at home
Melanoma
Adjuvant pembrolizumab: durable RFS for stage III melanoma
Adjuvant pembrolizumab: durable RFS for stage III melanoma
Pembrolizumab plus low-dose ipilimumab well tolerated after progression on PD1 antibody therapy
Toripalimab plus axitinib effective in metastatic mucosal melanoma
Breast & Ovarian Cancer
Advanced breast cancer: locoregional therapy does not improve OS
T-DM1 does not improve safety or efficacy in HER-2 positive early breast cancer; favorable iDFS reported
Maintenance olaparib improves OS in relapsed ovarian cancer with BRCA1/2 mutation
Combination pembrolizumab/chemo improves PFS in metastatic TNBC
Effect of veliparib with or without cisplatin in breast cancer: results of SWOG S1416
PHOEBE, a phase 3 trial comparing pyrotinib and lapatinib in HER2-positive metastatic breast cancer
BYLieve demonstrates efficacy of PIK3CA-directed treatment post CDK4/6-ihibition
Strategies emerge for chemotherapy de-escalation in HER2-positive breast cancer
Multiple Myeloma
Carfilzomib: no PFS benefit for multiple myeloma
Lung Cancer
ES-SCLC: tremelimumab + durvalumab + chemotherapy misses endpoint
Adjuvant osimertinib in NSCLC: practice changing ADAURA trial
ES-SCLC: pembrolizumab KEYNOTE-604 data
Second-line gemcitabine plus ramucirumab significantly improves overall survival
Tiragolumab and atezolizumab: ORR in NSCLC
MET-amplified advanced NSCLC responds well to MET inhibitor capmatinib
Genitourinary Cancer
Urothelial cancer: avelumab works as maintenance therapy
ARAMIS final OS and nmCRPC safety outcomes
Final survival results from phase 3 SPARTAN trial
Novel drug for kidney cancers/VHL patients
Primary analysis from IMvigor010, adjuvant atezolizumab in high risk muscle-invasive urothelial carcinoma
First randomised trial of Lu-PSMA in mCRPC progressing after docetaxel
Gastrointestinal Cancer
HER2-expressing metastatic colorectal cancer: trastuzumab deruxtecan
REGOMUNE: a phase 2 study combining regorafenib and avelumab
Cardiotoxicity: consider switching to S-1
Perioperative chemotherapy for resectable pancreatic ductal adenocarcinoma
Real-world data of sequential sorafenib followed by regorafenib in unresectable HCC
Paediatric Cancer
Sustained improvements in quality of life with larotrectinib
Promising first immunotherapy trial in placental trophoblastic tumours
Precision medicine for poor-prognosis paediatric patients
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