BACKGROUND: Combination therapy with immune checkpoint inhibitors (ICIs) and antiangiogenic agents is generally effective and well tolerated and might be effective for metastatic urothelial carcinoma (UC). However, ICI treatment is often associated with unique responses, such as pseudoprogression and ICI-related pneumonitis (CIP), which may influence clinical decision making and affect treatment. Although there have been many studies on the mechanism of pseudoprogression and CIP, the characteristics and relationship of these special events in a clinical setting remain rarely reported. CASE PRESENTATION: Here, we present a patient with lung metastatic UC who underwent surgery and two lines of chemotherapy. The programmed cell death-1 (PD-1) inhibitor nivolumab and antiangiogenics agent bevacizumab were used as maintenance treatments. The patient experienced pseudoprogression after 2 PD-1 inhibitor cycles. The lesions in both lungs were enlarged on computed tomography (CT) imaging, and treatments were continued for another two cycles, after which the tumor size decreased to below baseline, followed by a durable response. However, after 4 months of pseudoprogression, the patient then developed CIP. The CIP was responsive to glucocorticoid therapy but recurred during ICI rechallenge, leading to the termination of immune therapy. Ultimately, the patient achieved durable, stable disease for over 18 months without further anticancer treatment. CONCLUSIONS: Our case shows that pseudoprogression can occur in UC during immunotherapy even when combined with an effective antiangiogenic agent. In addition, pseudoprogression may be correlated with future adverse effects and a durable response. In the management of CIP, early rechallenge with ICIs may lead to CIP recurrence, which could be more severe and needs to be treated early and with appropriate drugs. Clinicians should be aware of atypical responses to ICIs and adjust the treatment plan accordingly.
BACKGROUND: Combination therapy with immune checkpoint inhibitors (ICIs) and antiangiogenic agents is generally effective and well tolerated and might be effective for metastatic urothelial carcinoma (UC). However, ICI treatment is often associated with unique responses, such as pseudoprogression and ICI-related pneumonitis (CIP), which may influence clinical decision making and affect treatment. Although there have been many studies on the mechanism of pseudoprogression and CIP, the characteristics and relationship of these special events in a clinical setting remain rarely reported. CASE PRESENTATION: Here, we present a patient with lung metastatic UC who underwent surgery and two lines of chemotherapy. The programmed cell death-1 (PD-1) inhibitor nivolumab and antiangiogenics agent bevacizumab were used as maintenance treatments. The patient experienced pseudoprogression after 2 PD-1 inhibitor cycles. The lesions in both lungs were enlarged on computed tomography (CT) imaging, and treatments were continued for another two cycles, after which the tumor size decreased to below baseline, followed by a durable response. However, after 4 months of pseudoprogression, the patient then developed CIP. The CIP was responsive to glucocorticoid therapy but recurred during ICI rechallenge, leading to the termination of immune therapy. Ultimately, the patient achieved durable, stable disease for over 18 months without further anticancer treatment. CONCLUSIONS: Our case shows that pseudoprogression can occur in UC during immunotherapy even when combined with an effective antiangiogenic agent. In addition, pseudoprogression may be correlated with future adverse effects and a durable response. In the management of CIP, early rechallenge with ICIs may lead to CIP recurrence, which could be more severe and needs to be treated early and with appropriate drugs. Clinicians should be aware of atypical responses to ICIs and adjust the treatment plan accordingly.
Authors: Julie R Brahmer; Christina Lacchetti; Bryan J Schneider; Michael B Atkins; Kelly J Brassil; Jeffrey M Caterino; Ian Chau; Marc S Ernstoff; Jennifer M Gardner; Pamela Ginex; Sigrun Hallmeyer; Jennifer Holter Chakrabarty; Natasha B Leighl; Jennifer S Mammen; David F McDermott; Aung Naing; Loretta J Nastoupil; Tanyanika Phillips; Laura D Porter; Igor Puzanov; Cristina A Reichner; Bianca D Santomasso; Carole Seigel; Alexander Spira; Maria E Suarez-Almazor; Yinghong Wang; Jeffrey S Weber; Jedd D Wolchok; John A Thompson Journal: J Clin Oncol Date: 2018-02-14 Impact factor: 44.544
Authors: F Stephen Hodi; Donald Lawrence; Cecilia Lezcano; Xinqi Wu; Jun Zhou; Tetsuro Sasada; Wanyong Zeng; Anita Giobbie-Hurder; Michael B Atkins; Nageatte Ibrahim; Philip Friedlander; Keith T Flaherty; George F Murphy; Scott Rodig; Elsa F Velazquez; Martin C Mihm; Sara Russell; Pamela J DiPiro; Jeffrey T Yap; Nikhil Ramaiya; Annick D Van den Abbeele; Maria Gargano; David McDermott Journal: Cancer Immunol Res Date: 2014-04-21 Impact factor: 11.151
Authors: Padmanee Sharma; Margaret K Callahan; Petri Bono; Joseph Kim; Pavlina Spiliopoulou; Emiliano Calvo; Rathi N Pillai; Patrick A Ott; Filippo de Braud; Michael Morse; Dung T Le; Dirk Jaeger; Emily Chan; Chris Harbison; Chen-Sheng Lin; Marina Tschaika; Alex Azrilevich; Jonathan E Rosenberg Journal: Lancet Oncol Date: 2016-10-09 Impact factor: 41.316
Authors: Eun Young Kim; Inkeun Park; Young Saing Kim; Hee Kyung Ahn; Hee Young Lee; Jeong Ho Kim Journal: Thorac Cancer Date: 2019-02-07 Impact factor: 3.500
Authors: Changhee Park; Bhumsuk Keam; Soon Ho Yoon; Chan-Young Ock; Sun Mi Choi; Miso Kim; Young Sik Park; Tae Min Kim; Do-Youn Oh; Dong-Wan Kim; Young Whan Kim; Dae Seog Heo; Yung-Jue Bang Journal: ESMO Open Date: 2019-11-28