Second-line avelumab is effective in patients with MSI-H/dMMR mCRC

Avelumab administration in the second line improved progression-free survival (PFS) in patients with microsatellite instability-high (MSI-H)/ DNA mismatch repair-deficient (dMMR) metastatic colorectal cancer (mCRC) who are naïve to immune checkpoint inhibition, results from the SAMCO-PRODIGE 54 trial demonstrated.

MSI-high/dMMR colorectal tumours are currently the only colorectal tumours sensitive to immune checkpoint inhibition with pembrolizumab improving PFS in the first-line setting [1,2]. The phase 2 SAMCO-PRODIGE 54 trial (NCT03186326), presented by Prof. Julien Taieb (Hopital European George Pompidou, France), evaluated the efficacy of avelumab in the second-line for patients with MSI-high/dMMR mCRC versus standard-of-care [3].

The open-label, phase 2 trial randomised 122 patients with MSI-high/dMMR mCRC who progressed on oxaliplatin- or irinotecan-based first-line therapy (and targeted agents if indicated) to avelumab (10 mg/kg every 2 weeks) or standard second-line chemotherapy. The primary endpoint was PFS.

Due to Kaplan-Meier PFS curves crossing at 7.3 months, the log-rank test and HR assessment of treatment were invalid. Instead, the 2-stage procedure according to Qiu and Sheng was performed [4]. Second-line avelumab improved PFS significantly versus standard-of-care (P=0.025). PFS rates were 31% versus 19% at 12 months, 27% versus 9% at 18 months, and 25% versus 3% at 24 months for avelumab and standard-of-care, respectively. Objective response rates and disease control rates were similar between the treatment arms; however, disease control was maintained for 18 months with avelumab in most patients. Treatment with avelumab led to lower rates of grade ≥3 adverse events.

“This trial demonstrated that avelumab is safe and effective when used in the second-line in patients with MSI-high/dMMR mCRC, confirming that immune checkpoint inhibition remains relevant beyond first-line in patients naïve to immune checkpoint inhibition. However, the indirect comparison suggests that these patients should be treated with immune checkpoint inhibitors as soon as possible,” stated Prof. Taieb.  Indeed, the phase 3 KEYNOTE-177 trial confirms the effects of first-line pembrolizumab for this population of MSI-H CRC.

1. Eng C, et al. Lancet Oncol. 2019;20(6)849–861.
2. André T, et al. N Engl J Med. 2020;383(23);2207–2218.
3. Taieb J, et al. Avelumab versus standard second-line treatment chemotherapy in metastatic colorectal cancer (mCRC) patients with microsatellite instability (MSI): The SAMCO-PRODIGE 54 randomised phase II trial. Abstract LBA23, ESMO Congress 2022, 09–13 September Paris, France.
4. Qiu P, Sheng J. J R Stat Soc Ser B Stat Methodol. 2008;70:191–208.
5. André T, et al. N Engl J Med. 2020;383(23):2207-2218.

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Posted on 16 November, 202228 March, 2024