Raphael Colle1, Anna Radzik2, Romain Cohen3, Anna Pellat4, Daniel Lopez-Tabada4, Marine Cachanado5, Alex Duval6, Magali Svrcek7, Yves Menu2, Thierry André8. 1. Sorbonne Université, Department of Medical Oncology, Saint-Antoine Hospital, AP-HP, 184 Rue Du Faubourg Saint-Antoine, 75012, Paris, France; Sorbonne University, Clinical Research Unit, Saint-Antoine Hospital, AP-HP, 184 Rue Du Faubourg Saint-Antoine, 75012, Paris, France. 2. Sorbonne University, Department of Radiology, Saint-Antoine Hospital, AP-HP, 184 Rue Du Faubourg Saint-Antoine, 75012, Paris, France. 3. Sorbonne Université, Department of Medical Oncology, Saint-Antoine Hospital, AP-HP, 184 Rue Du Faubourg Saint-Antoine, 75012, Paris, France; Sorbonne University, INSERM UMRS_938, Microsatellite Instability and Cancer, Saint-Antoine Research Center, 184 Rue Du Faubourg Saint-Antoine, 75012, Paris, France. 4. Sorbonne Université, Department of Medical Oncology, Saint-Antoine Hospital, AP-HP, 184 Rue Du Faubourg Saint-Antoine, 75012, Paris, France. 5. Sorbonne University, Clinical Research Unit, Saint-Antoine Hospital, AP-HP, 184 Rue Du Faubourg Saint-Antoine, 75012, Paris, France. 6. Sorbonne University, INSERM UMRS_938, Microsatellite Instability and Cancer, Saint-Antoine Research Center, 184 Rue Du Faubourg Saint-Antoine, 75012, Paris, France. 7. Sorbonne University, INSERM UMRS_938, Microsatellite Instability and Cancer, Saint-Antoine Research Center, 184 Rue Du Faubourg Saint-Antoine, 75012, Paris, France; Sorbonne University, Department of Pathology, Saint-Antoine Hospital, AP-HP, 184 Rue Du Faubourg Saint-Antoine, 75012, Paris, France. 8. Sorbonne Université, Department of Medical Oncology, Saint-Antoine Hospital, AP-HP, 184 Rue Du Faubourg Saint-Antoine, 75012, Paris, France; Sorbonne University, Department of Radiology, Saint-Antoine Hospital, AP-HP, 184 Rue Du Faubourg Saint-Antoine, 75012, Paris, France; Sorbonne University, INSERM UMRS_938, Microsatellite Instability and Cancer, Saint-Antoine Research Center, 184 Rue Du Faubourg Saint-Antoine, 75012, Paris, France. Electronic address: thierry.andre@aphp.fr.
Abstract
BACKGROUND: The efficacy of immune checkpoint inhibitors (ICIs) in microsatellite instability-high/DNA mismatch repair (MSI/dMMR) metastatic colorectal cancer (mCRC) is well established. ICIs are responsible for pseudoprogression (PSPD) that complicates clinical decisions. We evaluated the PSPD frequency in patients with MSI/dMMR mCRC treated with ICIs. PATIENTS AND METHODS: Consecutive patients with MSI/dMMR mCRC treated with ICIs from February 2015 to December 2019 at Saint-Antoine Hospital were included. Imaging was retrospectively and centrally reviewed according to Response Evaluation Criteria in Solid Tumours, version 1.1 (RECIST 1.1) and immune RECIST (iRECIST). PSPD was defined as an unconfirmed disease progression by iRECIST. RESULTS: One hundred twenty-three patients with MSI/dMMR mCRC were included. Thirty-six patients (29%) had radiological PD according to RECIST 1.1 during the median follow-up of 22.3 months (95% confidence interval [CI], 1.5-62.2), including 22 in the first 3 months (the primary radiological PD). Twenty-nine patients continued ICIs beyond PD. Twelve patients experienced PSPD, representing 10% of the population and 52% of the primary radiological PD. The median time to PSPD was 5.7 weeks (95% CI, 4.1-11.4). No PSPD was observed after 3 months. The PSPD incidence was 14.8% in patients treated with anti-PD1 alone (n = 9/61) and 4.8% in case of anti-PD1 plus anti-CTLA-4 (n = 3/62). Eight patients with PSPD experienced an objective response. The 2-year progression-free survival and overall survival rates for patients with PSPD were 70.0% (95% CI, 32.9-89.2) and 75.0% (95% CI, 29.8-93.4), respectively. CONCLUSION: Patients with MSI/dMMR mCRC treated with ICIs experienced PSPDs. PSPD occurred within the first 3 months and represented most of the primary radiological PDs. The use of iRECIST criteria should be questioned after 3 months.
BACKGROUND: The efficacy of immune checkpoint inhibitors (ICIs) in microsatellite instability-high/DNA mismatch repair (MSI/dMMR) metastatic colorectal cancer (mCRC) is well established. ICIs are responsible for pseudoprogression (PSPD) that complicates clinical decisions. We evaluated the PSPD frequency in patients with MSI/dMMR mCRC treated with ICIs. PATIENTS AND METHODS: Consecutive patients with MSI/dMMR mCRC treated with ICIs from February 2015 to December 2019 at Saint-Antoine Hospital were included. Imaging was retrospectively and centrally reviewed according to Response Evaluation Criteria in Solid Tumours, version 1.1 (RECIST 1.1) and immune RECIST (iRECIST). PSPD was defined as an unconfirmed disease progression by iRECIST. RESULTS: One hundred twenty-three patients with MSI/dMMR mCRC were included. Thirty-six patients (29%) had radiological PD according to RECIST 1.1 during the median follow-up of 22.3 months (95% confidence interval [CI], 1.5-62.2), including 22 in the first 3 months (the primary radiological PD). Twenty-nine patients continued ICIs beyond PD. Twelve patients experienced PSPD, representing 10% of the population and 52% of the primary radiological PD. The median time to PSPD was 5.7 weeks (95% CI, 4.1-11.4). No PSPD was observed after 3 months. The PSPD incidence was 14.8% in patients treated with anti-PD1 alone (n = 9/61) and 4.8% in case of anti-PD1 plus anti-CTLA-4 (n = 3/62). Eight patients with PSPD experienced an objective response. The 2-year progression-free survival and overall survival rates for patients with PSPD were 70.0% (95% CI, 32.9-89.2) and 75.0% (95% CI, 29.8-93.4), respectively. CONCLUSION:Patients with MSI/dMMR mCRC treated with ICIs experienced PSPDs. PSPD occurred within the first 3 months and represented most of the primary radiological PDs. The use of iRECIST criteria should be questioned after 3 months.
Authors: Luis A Diaz; Kai-Keen Shiu; Tae-Won Kim; Benny Vittrup Jensen; Lars Henrik Jensen; Cornelis Punt; Denis Smith; Rocio Garcia-Carbonero; Manuel Benavides; Peter Gibbs; Christelle de la Fourchardiere; Fernando Rivera; Elena Elez; Dung T Le; Takayuki Yoshino; Wen Yan Zhong; David Fogelman; Patricia Marinello; Thierry Andre Journal: Lancet Oncol Date: 2022-04-12 Impact factor: 54.433