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Abstract：
BACKGROUND: PD-1/PD-L1 immune checkpoint inhibitors (ICIs) are widely used in the treatment of metastatic malignancies. Judiciously balancing disease control (DC) against development of immune-related adverse events (irAE) remains a crucial aspect of treatment. The effect of treatment discontinuation after sustained disease control (SDC) is unknown. The purpose of this analysis was to evaluate outcomes of responders to ICI who discontinue treatment after a minimum of 12 months (SDC).
METHODS: We retrospectively reviewed the database of the University of New Mexico Comprehensive Cancer Center (UNMCCC) between 2014 and 2021 and identified patients who had received ICI. Patients with metastatic solid tumors who had stopped ICI therapy after achieving SDC [stable disease, partial response, complete response (SD, PR, CR)] were selected and outcomes reviewed from their electronic health records.
RESULTS: We identified 204 patients who were treated with ICI for various solid cancers. Forty-four patients (21.6%) met the criteria, of whom 35 with follow-up data were included in the final analysis; including 11 melanoma, 5 non-small cell lung, 4 head & neck, 8 renal, 4 urothelial, 1 anal, 1 Merkel cell carcinoma, and 1 liposarcoma. Patients were divided into two groups: those who stopped ICI due to an irAE [irAE group, n = 14, median treatment time (MTT), 16.6 mo] and those who stopped due to other reasons (eg completion of 2 years of therapy, n = 20, non-cancer related surgery, n = 1) (non-irAE group, n = 21, MTT, 23.7 mo). Among the irAE group, the most common irAE included pneumonitis, rash, transaminitis, and fatigue. As of data cutoff date, 9 of 14 (64%) patients continued to show SDC. Only 5 of 14 (36%) patients in this group experienced progression of disease (PD), with 1 of 2 patients achieving DC (median follow-up of 19.2 mo after last dose of treatment, range 3-50.2 mo). Among the non-irAE group, 13 of 21 (62%) continued to have SDC. Eight of 21 (38%) experienced PD after stopping treatment, 7 of whom received ICI rechallenge, with 2 of 7 achieving DC (median follow-up of 22.2 mo, range 3.6-54.8 mo). At a median follow-up of 21.3 mo from stopping ICI therapy (range, 3-54.8 mo), 10 patients (71%) from the irAE group and 13 (61.9%) from the non-irAE group are in DC and have not experienced PD.
CONCLUSIONS: We demonstrate that 22 (66%) patients experienced SDC, regardless of cancer type or development of irAE. After including patients who were re-challenged with ICI due to PD, 25 (71%) remain in DC. Future prospective malignancy-specific trials are warranted to evaluate optimal treatment duration.
METHODS: We retrospectively reviewed the database of the University of New Mexico Comprehensive Cancer Center (UNMCCC) between 2014 and 2021 and identified patients who had received ICI. Patients with metastatic solid tumors who had stopped ICI therapy after achieving SDC [stable disease, partial response, complete response (SD, PR, CR)] were selected and outcomes reviewed from their electronic health records.
RESULTS: We identified 204 patients who were treated with ICI for various solid cancers. Forty-four patients (21.6%) met the criteria, of whom 35 with follow-up data were included in the final analysis; including 11 melanoma, 5 non-small cell lung, 4 head & neck, 8 renal, 4 urothelial, 1 anal, 1 Merkel cell carcinoma, and 1 liposarcoma. Patients were divided into two groups: those who stopped ICI due to an irAE [irAE group, n = 14, median treatment time (MTT), 16.6 mo] and those who stopped due to other reasons (eg completion of 2 years of therapy, n = 20, non-cancer related surgery, n = 1) (non-irAE group, n = 21, MTT, 23.7 mo). Among the irAE group, the most common irAE included pneumonitis, rash, transaminitis, and fatigue. As of data cutoff date, 9 of 14 (64%) patients continued to show SDC. Only 5 of 14 (36%) patients in this group experienced progression of disease (PD), with 1 of 2 patients achieving DC (median follow-up of 19.2 mo after last dose of treatment, range 3-50.2 mo). Among the non-irAE group, 13 of 21 (62%) continued to have SDC. Eight of 21 (38%) experienced PD after stopping treatment, 7 of whom received ICI rechallenge, with 2 of 7 achieving DC (median follow-up of 22.2 mo, range 3.6-54.8 mo). At a median follow-up of 21.3 mo from stopping ICI therapy (range, 3-54.8 mo), 10 patients (71%) from the irAE group and 13 (61.9%) from the non-irAE group are in DC and have not experienced PD.
CONCLUSIONS: We demonstrate that 22 (66%) patients experienced SDC, regardless of cancer type or development of irAE. After including patients who were re-challenged with ICI due to PD, 25 (71%) remain in DC. Future prospective malignancy-specific trials are warranted to evaluate optimal treatment duration.
摘要：
背景：PD-1/PD-L1免疫检查点抑制剂（ICIs）广泛用于治疗转移性恶性肿瘤。合理地平衡疾病控制（DC）与免疫相关不良事件（irAE）的发展仍然是治疗的关键方面。持续疾病控制（SDC）后停止治疗的效果尚不清楚。该分析的目的是评估ICI应答者在至少12个月(SDC)后停止治疗的结果。
方法：我们回顾性回顾了2014年至2021年新墨西哥大学综合癌症中心（UNMCCC）的数据库，并确定了接受ICI的患者。转移性实体瘤患者在获得SDC后停止ICI治疗[疾病稳定，部分响应,完全反应(SD，PR,选择CR)]，并从他们的电子健康记录中审查结果。
结果：我们确定了204例接受ICI治疗的各种实体癌患者。44名患者(21.6%)符合标准,其中35例随访数据被纳入最终分析；包括11例黑色素瘤，5非小细胞肺，4头和脖子，8肾，4尿路上皮，1肛门，1默克尔细胞癌，和1个脂肪肉瘤.患者分为两组：因irAE而停止ICI的患者[irAE组，n=14，中位治疗时间（MTT），16.6mo]和因其他原因停止治疗的人（例如完成2年的治疗，n=20，非癌症相关手术，n=1)(非IRAE组，n=21，MTT，23.7个月）。在irAE组中，最常见的irAE包括肺炎，皮疹,转胺炎,和疲劳。截至数据截止日期，14名患者中有9名(64%)继续显示SDC。该组中只有14名患者中的5名（36％）经历了疾病进展（PD），2例患者中有1例达到DC（最后一次治疗后中位随访19.2个月，范围3-50.2个月）。在非IRAE组中，21个中的13个（62％）继续拥有SDC。21人中有8人（38%）在停止治疗后出现PD，其中7人接受了ICI的重新挑战，7人中有2人达到DC(中位随访时间为22.2个月，范围3.6-54.8个月）。在停止ICI治疗的中位随访21.3个月(范围，3-54.8个月),来自irAE组的10名患者(71%)和来自非irAE组的13名患者(61.9%)在DC中并且没有经历PD。
结论：我们证明22（66％）患者经历了SDC，无论癌症类型或irAE的发展。在包括因PD再次接受ICI治疗的患者后，25（71％）保留在DC中。未来的前瞻性恶性肿瘤特异性试验有必要评估最佳治疗持续时间。
方法：我们回顾性回顾了2014年至2021年新墨西哥大学综合癌症中心（UNMCCC）的数据库，并确定了接受ICI的患者。转移性实体瘤患者在获得SDC后停止ICI治疗[疾病稳定，部分响应,完全反应(SD，PR,选择CR)]，并从他们的电子健康记录中审查结果。
结果：我们确定了204例接受ICI治疗的各种实体癌患者。44名患者(21.6%)符合标准,其中35例随访数据被纳入最终分析；包括11例黑色素瘤，5非小细胞肺，4头和脖子，8肾，4尿路上皮，1肛门，1默克尔细胞癌，和1个脂肪肉瘤.患者分为两组：因irAE而停止ICI的患者[irAE组，n=14，中位治疗时间（MTT），16.6mo]和因其他原因停止治疗的人（例如完成2年的治疗，n=20，非癌症相关手术，n=1)(非IRAE组，n=21，MTT，23.7个月）。在irAE组中，最常见的irAE包括肺炎，皮疹,转胺炎,和疲劳。截至数据截止日期，14名患者中有9名(64%)继续显示SDC。该组中只有14名患者中的5名（36％）经历了疾病进展（PD），2例患者中有1例达到DC（最后一次治疗后中位随访19.2个月，范围3-50.2个月）。在非IRAE组中，21个中的13个（62％）继续拥有SDC。21人中有8人（38%）在停止治疗后出现PD，其中7人接受了ICI的重新挑战，7人中有2人达到DC(中位随访时间为22.2个月，范围3.6-54.8个月）。在停止ICI治疗的中位随访21.3个月(范围，3-54.8个月),来自irAE组的10名患者(71%)和来自非irAE组的13名患者(61.9%)在DC中并且没有经历PD。
结论：我们证明22（66％）患者经历了SDC，无论癌症类型或irAE的发展。在包括因PD再次接受ICI治疗的患者后，25（71％）保留在DC中。未来的前瞻性恶性肿瘤特异性试验有必要评估最佳治疗持续时间。
