Most Read Articles
27 Nov 2017
The amino sulphonic acid taurine may safely and effectively reduce portal pressure in cirrhotic patients, a study has shown.
Prof. Vincent Wong, Prof. Ray Kim, Dr. Tan Poh Seng, 10 Sep 2019
Chronic hepatitis B (CHB) remains a major public health concern because of its worldwide distribution and potential adverse sequelae, including cirrhosis and hepatocellular carcinoma (HCC). At a recent symposium held during the GIHep Singapore 2019, Professor Vincent Wong from the Chinese University of Hong Kong and Professor Ray Kim from the Stanford University School of Medicine, Stanford, California, US, discussed antiviral treatments for CHB, with a focus on the novel agent tenofovir alafenamide (Vemlidy®). Dr Tan Poh Seng from the National University Hospital, Singapore, chaired the symposium.
26 Nov 2019
Podcast: Professor R. Scott Wright speaks about the potential role of inclisiran in providing durable reductions in LDL-cholesterol levels in patients with atherosclerotic cardiovascular disease.
Jairia Dela Cruz, 12 Dec 2019
Use of isatuximab (Isa) in combination with pomalidomide and dexamethasone (PomDex) appears to lead to more favourable outcomes in elderly patients with relapsed/refractory multiple myeloma (RRMM) as compared with PomDex alone, according to the results of a subgroup analysis of the ICARIA-MM trial presented at the 61st Annual Meeting of the American Society of Hematology (ASH 2019).

Nivolumab-ipilimumab combo demonstrates potential in dMMR/MSI-H metastatic CRC

Roshini Claire Anthony
06 Feb 2018

The combination of nivolumab and ipilimumab demonstrated strong response, progression-free survival (PFS), and overall survival (OS) rates in patients with DNA mismatch repair-deficient/microsatellite instability-high (dMMR/MSI-H) metastatic or recurrent colorectal cancer (CRC), results from the phase II CheckMate-142* trial show.

“Nivolumab plus ipilimumab represents a promising new treatment option for patients with previously treated dMMR/MSI-H metastatic CRC,” said Dr Thierry André from the Hôpital Saint Antoine and Sorbonne Universités, Paris, France, who presented the findings at the ASCO 2018 Gastrointestinal Cancers Symposium (ASCO GI 2018).

A total of 119 patients with dMMR/MSI-H metastatic or recurrent CRC with ECOG status ≤1 who had undergone ≥1 prior lines of therapy received four intravenous infusion doses of nivolumab (3 mg/kg) plus ipilimumab (1 mg/kg) Q3W followed by nivolumab (3 mg/kg Q2W, median age 58 years, 59 percent male). Of these, 76 percent of patients had ≥2 prior lines of therapy, the most common therapies being fluoropyrimidine (99 percent), oxaliplatin (93 percent), and irinotecan (73 percent).

Investigator-assessed objective response rate (ORR) was 54.6 percent at the 13.4-month median follow-up point, with 3.4 and 51.3 percent of patients achieving complete and partial response, respectively. Responses were observed regardless of tumour BRAF or KRAS mutation status, PD-L1 expression, or history of Lynch syndrome. [ASCO GI 2018, abstract 553; J Clin Oncol 2018;doi:10.1200/JCO.2017.76.9901]

Disease control rate for ≥12 weeks was 80 percent which was superior to that seen in a separate group of 74 patients receiving nivolumab monotherapy (3 mg/kg Q2W; 69 percent). Seventy-eight percent of patients on combination therapy experienced a reduction in tumour burden from baseline.

The median time to response was 2.8 months and median duration of response was not reached with 94 percent of responders still responding at data cut-off point. At 12 months, PFS and OS rates were 71 and 85 percent, respectively.

Thirty-seven percent of patients (n=44) discontinued treatment, a majority due to disease progression (n=23) or study drug-related adverse events (AEs; n=16).

Grade 3–4 treatment-related AEs (TRAEs) occurred in 32 percent of patients, with the most common AE being elevated AST and ALT levels (8 and 7 percent, respectively). Ten percent of patients demonstrated grade 3–4 TRAEs that led to discontinuation.

According to the researchers, patients with dMMR/MSI-H metastatic CRC tend to benefit less from conventional chemotherapy compared with patients who are MMR-proficient or microsatellite stable.

While this nonrandomized trial was not designed to compare the combination therapy with nivolumab monotherapy, indirect comparisons point towards a numerically higher ORR with the nivolumab plus ipilimumab combination (55 percent vs 31 percent) as well as better median 12-month PFS and OS (71 percent vs 50 percent [PFS] and 85 percent vs 73 percent [OS]). [Lancet Oncol 2017;18:1182-1191]

“Although the development of PD-1 inhibitors provided an important advance in the treatment of patients with dMMR/MSI-H metastatic CRC, an opportunity remains to explore rational combinations to further improve these results … The favourable benefit-risk profile seen in this cohort suggests a role for combination checkpoint inhibitor therapy in the treatment of patients with dMMR/MSI-H metastatic CRC,” said the researchers, highlighting that further studies are required to establish this finding.

Despite the positive outcomes, the significance of these findings needs to be taken into consideration, said Dr Zsofia Kinga Stadler from the Memorial Sloan Kettering Cancer Center who discussed the findings at ASCO GI 2018.

“It’s unclear if combination immunotherapy provides long-term clinical benefit over anti-PD-1 monotherapy. Further studies are needed to identify particular subgroups of patients who may benefit from combination therapy,” she said, pointing out that cost and value would also be important factors in this decision.

 

 

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Most Read Articles
27 Nov 2017
The amino sulphonic acid taurine may safely and effectively reduce portal pressure in cirrhotic patients, a study has shown.
Prof. Vincent Wong, Prof. Ray Kim, Dr. Tan Poh Seng, 10 Sep 2019
Chronic hepatitis B (CHB) remains a major public health concern because of its worldwide distribution and potential adverse sequelae, including cirrhosis and hepatocellular carcinoma (HCC). At a recent symposium held during the GIHep Singapore 2019, Professor Vincent Wong from the Chinese University of Hong Kong and Professor Ray Kim from the Stanford University School of Medicine, Stanford, California, US, discussed antiviral treatments for CHB, with a focus on the novel agent tenofovir alafenamide (Vemlidy®). Dr Tan Poh Seng from the National University Hospital, Singapore, chaired the symposium.
26 Nov 2019
Podcast: Professor R. Scott Wright speaks about the potential role of inclisiran in providing durable reductions in LDL-cholesterol levels in patients with atherosclerotic cardiovascular disease.
Jairia Dela Cruz, 12 Dec 2019
Use of isatuximab (Isa) in combination with pomalidomide and dexamethasone (PomDex) appears to lead to more favourable outcomes in elderly patients with relapsed/refractory multiple myeloma (RRMM) as compared with PomDex alone, according to the results of a subgroup analysis of the ICARIA-MM trial presented at the 61st Annual Meeting of the American Society of Hematology (ASH 2019).