Urothelial cancer: Less gained from immunotherapy in patients with poor performance scores

Patients with advanced urothelial cancer and a poor performance status may have little to gain from immune checkpoint inhibitor therapy, suggests a multicenter real-world retrospective cohort study.

“The perceived favorable toxicity profile of immune checkpoint inhibitors has led to the selection of these agents for patients otherwise unfit for systemic chemotherapy,” noted the investigators, led by Ali Raza Khaki, MD, a fellow in the division of oncology, department of medicine, University of Washington, Seattle. “However, there is a paucity of data supporting the use of immune checkpoint inhibitors in patients with a poor performance status, who were not very well represented in the clinical trials that led to their approval, with no trial enrolling patients with an ECOG [Eastern Cooperative Oncology Group] performance status greater than or equal to 3 and only 3 trials including patients with an ECOG performance status of 2.”

Dr. Khaki and coinvestigators analyzed data from 499 patients with advanced urothelial cancer treated with immune checkpoint inhibitors at 18 institutions during 2013-2019. Slightly more than one-quarter had an ECOG performance status of 2 or higher.

Study results, reported in Cancer, showed that the overall response rate to immune checkpoint inhibitor therapy was similar regardless of performance status, across patients being treated in different lines of therapy.

However, among patients being treated in the first line, overall survival was better for those with a performance status of 0 to 1 than for those with a performance status of 2 or higher (median, 15.2 vs. 7.2 months; hazard ratio for death, 0.62; P = .01). There was no significant difference in this outcome among patients being treated in subsequent lines (median, 9.8 vs. 8.2 months; hazard ratio, 0.78; P = .27).

Among the 288 patients who died, 10% started immune checkpoint inhibitors in the last 30 days of life and 33% started them in the last 90 days of life. Patients initiating this therapy in the last 30 days of life were almost three time more likely to die in a hospital (odds ratio, 2.89; P = .04).

 

Notably, among the 11 patients with an ECOG performance status of 3, none had a response to immune checkpoint inhibitors and only two achieved stable disease. Moreover, two patients in this subgroup died within a week of receiving these agents.

“Despite comparable overall response rates, immune checkpoint inhibitors may not overcome the negative prognostic role of a poor performance status, particularly in the first-line setting,” Dr. Khaki and coinvestigators wrote. “Our study underscores the importance of developing prospectively validated predictive biomarkers to aid in identifying those patients most and least likely to benefit from immune checkpoint inhibitors.

“Overall, our data suggest that the decision of immune checkpoint inhibitor initiation near the end of life, akin to the practice for chemotherapy, should be considered carefully, and it should be accompanied by a detailed discussion of the data, rationale, and risks and benefits to minimize unnecessary potential adverse events and the cost and intensity of end-of-life care,” they recommended.

Dr. Khaki did not disclose any conflicts of interest. The study was supported by the National Cancer Institute, the National Center for Advancing Translational Sciences of the National Institutes of Health, the Seattle Translational Tumor Research Program at the Fred Hutchinson Cancer Research Center, the Imperial Experimental Cancer Medicine Centre, the Cancer Research UK Imperial Centre, the Wellcome Trust Strategic Fund, and Merck.

SOURCE: Khaki AR et al. Cancer. 2019 Dec 12. doi: 10.1002/cncr.32645.

Patients with advanced urothelial cancer and a poor performance status may have little to gain from immune checkpoint inhibitor therapy, suggests a multicenter real-world retrospective cohort study.

“The perceived favorable toxicity profile of immune checkpoint inhibitors has led to the selection of these agents for patients otherwise unfit for systemic chemotherapy,” noted the investigators, led by Ali Raza Khaki, MD, a fellow in the division of oncology, department of medicine, University of Washington, Seattle. “However, there is a paucity of data supporting the use of immune checkpoint inhibitors in patients with a poor performance status, who were not very well represented in the clinical trials that led to their approval, with no trial enrolling patients with an ECOG [Eastern Cooperative Oncology Group] performance status greater than or equal to 3 and only 3 trials including patients with an ECOG performance status of 2.”

Dr. Khaki and coinvestigators analyzed data from 499 patients with advanced urothelial cancer treated with immune checkpoint inhibitors at 18 institutions during 2013-2019. Slightly more than one-quarter had an ECOG performance status of 2 or higher.

Study results, reported in Cancer, showed that the overall response rate to immune checkpoint inhibitor therapy was similar regardless of performance status, across patients being treated in different lines of therapy.

However, among patients being treated in the first line, overall survival was better for those with a performance status of 0 to 1 than for those with a performance status of 2 or higher (median, 15.2 vs. 7.2 months; hazard ratio for death, 0.62; P = .01). There was no significant difference in this outcome among patients being treated in subsequent lines (median, 9.8 vs. 8.2 months; hazard ratio, 0.78; P = .27).

Among the 288 patients who died, 10% started immune checkpoint inhibitors in the last 30 days of life and 33% started them in the last 90 days of life. Patients initiating this therapy in the last 30 days of life were almost three time more likely to die in a hospital (odds ratio, 2.89; P = .04).

 

Notably, among the 11 patients with an ECOG performance status of 3, none had a response to immune checkpoint inhibitors and only two achieved stable disease. Moreover, two patients in this subgroup died within a week of receiving these agents.

“Despite comparable overall response rates, immune checkpoint inhibitors may not overcome the negative prognostic role of a poor performance status, particularly in the first-line setting,” Dr. Khaki and coinvestigators wrote. “Our study underscores the importance of developing prospectively validated predictive biomarkers to aid in identifying those patients most and least likely to benefit from immune checkpoint inhibitors.

“Overall, our data suggest that the decision of immune checkpoint inhibitor initiation near the end of life, akin to the practice for chemotherapy, should be considered carefully, and it should be accompanied by a detailed discussion of the data, rationale, and risks and benefits to minimize unnecessary potential adverse events and the cost and intensity of end-of-life care,” they recommended.

Dr. Khaki did not disclose any conflicts of interest. The study was supported by the National Cancer Institute, the National Center for Advancing Translational Sciences of the National Institutes of Health, the Seattle Translational Tumor Research Program at the Fred Hutchinson Cancer Research Center, the Imperial Experimental Cancer Medicine Centre, the Cancer Research UK Imperial Centre, the Wellcome Trust Strategic Fund, and Merck.

SOURCE: Khaki AR et al. Cancer. 2019 Dec 12. doi: 10.1002/cncr.32645.

Patients with advanced urothelial cancer and a poor performance status may have little to gain from immune checkpoint inhibitor therapy, suggests a multicenter real-world retrospective cohort study.

“The perceived favorable toxicity profile of immune checkpoint inhibitors has led to the selection of these agents for patients otherwise unfit for systemic chemotherapy,” noted the investigators, led by Ali Raza Khaki, MD, a fellow in the division of oncology, department of medicine, University of Washington, Seattle. “However, there is a paucity of data supporting the use of immune checkpoint inhibitors in patients with a poor performance status, who were not very well represented in the clinical trials that led to their approval, with no trial enrolling patients with an ECOG [Eastern Cooperative Oncology Group] performance status greater than or equal to 3 and only 3 trials including patients with an ECOG performance status of 2.”

Dr. Khaki and coinvestigators analyzed data from 499 patients with advanced urothelial cancer treated with immune checkpoint inhibitors at 18 institutions during 2013-2019. Slightly more than one-quarter had an ECOG performance status of 2 or higher.

Study results, reported in Cancer, showed that the overall response rate to immune checkpoint inhibitor therapy was similar regardless of performance status, across patients being treated in different lines of therapy.

However, among patients being treated in the first line, overall survival was better for those with a performance status of 0 to 1 than for those with a performance status of 2 or higher (median, 15.2 vs. 7.2 months; hazard ratio for death, 0.62; P = .01). There was no significant difference in this outcome among patients being treated in subsequent lines (median, 9.8 vs. 8.2 months; hazard ratio, 0.78; P = .27).

Among the 288 patients who died, 10% started immune checkpoint inhibitors in the last 30 days of life and 33% started them in the last 90 days of life. Patients initiating this therapy in the last 30 days of life were almost three time more likely to die in a hospital (odds ratio, 2.89; P = .04).

 

Notably, among the 11 patients with an ECOG performance status of 3, none had a response to immune checkpoint inhibitors and only two achieved stable disease. Moreover, two patients in this subgroup died within a week of receiving these agents.

“Despite comparable overall response rates, immune checkpoint inhibitors may not overcome the negative prognostic role of a poor performance status, particularly in the first-line setting,” Dr. Khaki and coinvestigators wrote. “Our study underscores the importance of developing prospectively validated predictive biomarkers to aid in identifying those patients most and least likely to benefit from immune checkpoint inhibitors.

“Overall, our data suggest that the decision of immune checkpoint inhibitor initiation near the end of life, akin to the practice for chemotherapy, should be considered carefully, and it should be accompanied by a detailed discussion of the data, rationale, and risks and benefits to minimize unnecessary potential adverse events and the cost and intensity of end-of-life care,” they recommended.

Dr. Khaki did not disclose any conflicts of interest. The study was supported by the National Cancer Institute, the National Center for Advancing Translational Sciences of the National Institutes of Health, the Seattle Translational Tumor Research Program at the Fred Hutchinson Cancer Research Center, the Imperial Experimental Cancer Medicine Centre, the Cancer Research UK Imperial Centre, the Wellcome Trust Strategic Fund, and Merck.

SOURCE: Khaki AR et al. Cancer. 2019 Dec 12. doi: 10.1002/cncr.32645.