Lung Malignancy. higher were significantly shorter compared with those of PS 0\1 individuals (median PFS, 4.1 vs 2.0?weeks; valuetest. Except for PS, BMI was the only clinical factor that significantly differed between the groups. 3.2. Overall performance status 2 or higher is associated with poor survival in NSCLC individuals treated with ICIs Individuals with PS 0\1 experienced a significantly longer PFS than individuals with PS 2\4 (median PFS, 4.1 vs 2.0?weeks, respectively, valuevaluemutationPositive2.0091.509\2.673 .0011.5981.176\2.170.003WT or undetermined1.0001.000SmokingEx or current0.6150.483\0.783 .0010.6230.418\0.930.021Never1.0001.000PS2\41.8191.404\2.357 .0011.9081.465\2.484 .0010\11.0001.000Treatment collection2nd collection or later1.6851.262\2.250 .0011.6901.258\2.270 .0011st line1.0001.000 (B) GenderFemale1.0500.786\1.403.7410.6380.384\1.063.084Male1.0001.000StagingIII or IV1.3771.046\1.813.0231.3631.033\1.798.029Recurrence1.0001.000 mutationPositive1.3560.958\1.918.0861.2030.821\1.764.344WT or undetermined1.0001.000SmokingEx or current0.7830.579\1.060.1130.5540.324\0.949.031Never1.0001.000PS2\43.5262.641\4.709 .0013.9142.908\5.269 .0010\11.0001.000Treatment collection2nd collection or later1.4630.999\2.141.0501.5261.036\2.248.0331st line1.0001.000 Open in a separate window Abbreviations: CI, confidence interval; EGFR, epidermal growth factor receptor; HR, hazard ratio; PS, overall performance status. Similarly, patients with a worse PS experienced a significantly shorter OS. The median OS in patients with a PS of 0\1 and 2\4 was 17.4 and 4.0?months, respectively (Physique?1B). The OS was significantly shorter in patients in the PS 2\4 group than in the PS 0\1 group ( em P /em ? ?.001). Univariate (HR, 3.526; 95% CI, 2.641\4.709) and multivariate analyses (HR, 3.914; 95% CI, 2.908\5.269) revealed that a PS of 2\4 was an independent factor predicting short OS (Table?2B). To obtain further insight into the impact of PS on ICI therapy end result, we stratified patients into 4 groups according to their PS (PS 0, 1, 2, and 3\4) and undertook survival analysis for each individual group (Physique?2). The median PFS occasions in patients in the PS 0, 1, 2, and 3\4 groups were 6.9, 3.5, 2.3, and 1.1?months, respectively (Physique?2A). Furthermore, PFS was significantly shorter in patients with PS 1, 2, and 3\4 than patients with PS 0 (PS 1 vs PS 0: HR, 1.336; 95% CI, 1.031\1.732; em P /em ?=?.026; PS 2 vs PS 0: HR, 1.451; 95% CI, 1.214\1.734; em P /em ? ?.001; PS 3\4 vs PS 0: HR, 2.410; 95% CI, 1.772\3.277; em P /em ? ?.001). Similarly, OS was significantly shorter in patients with worse PS (Physique?2B). The median OS times in patients with PS 0, 1, 2, and 3\4 were 20.4, 15.5, 5.0, and 1.9?months, respectively (PS 1 vs PS 0: HR, 1.536; 95% CI, 1.092\2.160; em P /em ?=?.014; PS 2 vs PS 0: HR, 2.088; 95% CI, 1.682\2.593; em P /em ? ?.001; PS 3\4 vs PS 0: HR, 4.619; 95% CI, 3.034\7.032, em P /em ? ?.001). Open in a separate window Physique 2 A, Progression\free survival (PFS) of patients with non\small\cell lung malignancy treated with immune checkpoint inhibitors with overall performance status (PS) 0 (solid collection, n?=?103), PS 1 (dashed collection, n?=?345), PS 2 (dotted collection, n?=?64), or PS 3\4 (dashed and dotted collection, n?=?15). B, Overall survival (OS) of patients with PS 0 (solid collection, n?=?103), PS 1 (dashed collection, n?=?345), PS 2 (dotted collection, n?=?64), or PS 3\4 (dashed and dotted collection, n?=?15). CI, confidence interval 3.3. Characteristics of PS 2 patients who benefited from ICI therapy Although patients with PS 2 or higher experienced worse survival after ICI therapy than those with PS less than 2, some patients with PS 2 responded to ICI treatment, achieving disease control for more than 1?12 months. By contrast, all patients with PS 3\4 experienced disease progression or death in less than 10?months (Physique?2A). These observations suggest that certain patients with PS 2 could benefit from ICI therapy, despite their poor PS. Hence, we sought to assess the characteristics of patients with PS 2 who benefited from ICI therapy. Because the efficacies of pembrolizumab as a first\collection treatment for NSCLC patients with PD\L1 expression of 50% or higher and that of any ICIs as second\ or later\line treatments irrespective of PD\L1 expression in NSCLC patients are quite different, we stratified patients according to treatment strategy and compared the outcomes of patients with PS 2 and PS 0\1 (Physique?S1). Cohort 1 included patients with NSCLC (PD\L1 expression 50% or higher) treated with pembrolizumab as first\collection treatment (Table?S1), whereas cohort 2 included NSCLC patients with any PD\L1 expression who were treated with any ICI as second\ or later\collection therapy (Table?S2). Among patients with NSCLC with PD\L1 expression of 50% or higher who were treated with pembrolizumab as first\collection therapy (cohort 1), the median PFS for patients with PS 2 was 7.3?months (95% CI, 1.5\11.4?months), whereas that of patients with PS 0\1 was 8.1?months (95% CI, 4.8?monthsCnot reached) (Physique?3A). There was no significant difference in PFS between patients with PS 2 and PS 0\1 ( em P /em ?=?.321). However, patients with PS 3\4 experienced a PFS of 1 1.0?month (95% CI, 0.3?months\not reached) (Physique?3A), which was significantly worse than that of PS 0\1 patients ( em P /em ? ?.001). Comparable findings were observed for the OS (Physique?3B). The 1\12 months OS rates in.1998;83(3):847\850. experienced a significantly longer PFS than patients with PS 2\4 (median PFS, 4.1 vs 2.0?months, respectively, valuevaluemutationPositive2.0091.509\2.673 .0011.5981.176\2.170.003WT or undetermined1.0001.000SmokingEx or current0.6150.483\0.783 .0010.6230.418\0.930.021Never1.0001.000PS2\41.8191.404\2.357 .0011.9081.465\2.484 .0010\11.0001.000Treatment collection2nd collection or later1.6851.262\2.250 .0011.6901.258\2.270 .0011st line1.0001.000 (B) GenderFemale1.0500.786\1.403.7410.6380.384\1.063.084Male1.0001.000StagingIII or IV1.3771.046\1.813.0231.3631.033\1.798.029Recurrence1.0001.000 mutationPositive1.3560.958\1.918.0861.2030.821\1.764.344WT or undetermined1.0001.000SmokingEx or current0.7830.579\1.060.1130.5540.324\0.949.031Never1.0001.000PS2\43.5262.641\4.709 .0013.9142.908\5.269 .0010\11.0001.000Treatment collection2nd collection or later1.4630.999\2.141.0501.5261.036\2.248.0331st line1.0001.000 Open in a separate window Abbreviations: CI, confidence interval; EGFR, epidermal growth factor receptor; HR, hazard ratio; PS, overall performance status. Similarly, patients using a worse PS got a considerably shorter Operating-system. The median Operating-system in sufferers using a PS of 0\1 and 2\4 was 17.4 and 4.0?a few months, respectively (Body?1B). The Operating-system was considerably shorter in sufferers in the PS 2\4 group than in the PS 0\1 group ( em P /em ? ?.001). Univariate (HR, 3.526; 95% CI, 2.641\4.709) and multivariate analyses (HR, 3.914; 95% CI, 2.908\5.269) revealed a PS of 2\4 was an unbiased factor predicting short OS (Desk?2B). To acquire further insight Begacestat (GSI-953) in to the influence of PS on ICI therapy result, we stratified sufferers into 4 groupings according with their Begacestat (GSI-953) PS (PS 0, 1, 2, and 3\4) and undertook success analysis for every affected person group (Body?2). The median PFS moments in sufferers in the PS 0, 1, 2, and 3\4 groupings had been 6.9, 3.5, 2.3, and 1.1?a few months, respectively (Body?2A). Furthermore, PFS was considerably shorter in sufferers with PS 1, 2, and 3\4 than sufferers with PS 0 (PS 1 vs PS 0: HR, 1.336; 95% CI, 1.031\1.732; em P /em ?=?.026; PS 2 vs PS 0: HR, 1.451; 95% CI, 1.214\1.734; em P /em ? ?.001; PS 3\4 vs PS 0: HR, 2.410; 95% CI, 1.772\3.277; em P /em ? ?.001). Likewise, Operating-system was considerably shorter in sufferers with worse PS (Body?2B). The median Operating-system times in sufferers with PS 0, 1, 2, and 3\4 had been 20.4, 15.5, 5.0, and 1.9?a few months, respectively (PS 1 vs PS 0: HR, 1.536; 95% CI, 1.092\2.160; em P /em ?=?.014; PS 2 vs PS 0: HR, 2.088; 95% CI, 1.682\2.593; em P /em ? ?.001; PS 3\4 vs PS 0: HR, 4.619; 95% CI, 3.034\7.032, em P /em ? ?.001). Open up in another window Body 2 A, Development\free success (PFS) of sufferers with non\little\cell lung tumor treated with immune system checkpoint inhibitors with efficiency position (PS) 0 (solid range, n?=?103), PS 1 (dashed range, n?=?345), PS 2 (dotted range, n?=?64), or PS 3\4 (dashed and dotted range, n?=?15). B, General success (Operating-system) of sufferers with PS 0 (solid range, n?=?103), PS 1 (dashed range, n?=?345), PS 2 (dotted range, n?=?64), or PS 3\4 (dashed and dotted range, n?=?15). CI, self-confidence period 3.3. Features of PS 2 sufferers who benefited from ICI therapy Although sufferers with PS 2 or more got worse success after ICI therapy than people that have PS significantly less than 2, some sufferers with PS 2 taken care of immediately ICI treatment, attaining disease control for a lot more than 1?season. In comparison, all sufferers with PS 3\4 skilled disease development or death in under 10?a few months (Body?2A). These observations claim that specific sufferers with PS 2 could reap the benefits of ICI therapy, despite their poor PS. Therefore, we searched for to measure the features of sufferers with PS 2 who benefited from ICI therapy. As the efficacies of pembrolizumab being a initial\range treatment for NSCLC sufferers with PD\L1 appearance of 50% or more which of any ICIs as second\ or afterwards\line treatments regardless of PD\L1 appearance in NSCLC sufferers are very different, we stratified sufferers regarding to treatment technique and compared the final results of sufferers with PS 2 and PS 0\1 (Body?S1). Cohort 1 included sufferers with NSCLC (PD\L1 appearance 50% or more) treated with pembrolizumab as initial\range treatment (Desk?S1), whereas cohort 2 included NSCLC sufferers with any PD\L1 appearance who.2015;88(3):304\309. 4.1 vs 2.0?a few months; valuetest. Aside from PS, BMI was the just clinical aspect that considerably differed between your groupings. 3.2. Efficiency position 2 or better is connected with poor success in NSCLC sufferers treated with ICIs Sufferers with PS 0\1 got a significantly much longer PFS than sufferers with PS 2\4 (median PFS, 4.1 vs 2.0?weeks, respectively, valuevaluemutationPositive2.0091.509\2.673 .0011.5981.176\2.170.003WT or undetermined1.0001.000SmokingEx or current0.6150.483\0.783 .0010.6230.418\0.930.021Never1.0001.000PS2\41.8191.404\2.357 .0011.9081.465\2.484 .0010\11.0001.000Treatment range2nd range or later on1.6851.262\2.250 .0011.6901.258\2.270 .0011st line1.0001.000 (B) GenderFemale1.0500.786\1.403.7410.6380.384\1.063.084Male1.0001.000StagingIII or IV1.3771.046\1.813.0231.3631.033\1.798.029Recurrence1.0001.000 mutationPositive1.3560.958\1.918.0861.2030.821\1.764.344WT or undetermined1.0001.000SmokingEx or current0.7830.579\1.060.1130.5540.324\0.949.031Never1.0001.000PS2\43.5262.641\4.709 .0013.9142.908\5.269 .0010\11.0001.000Treatment range2nd range or later on1.4630.999\2.141.0501.5261.036\2.248.0331st line1.0001.000 Open up in another window Abbreviations: CI, confidence interval; EGFR, epidermal development element receptor; HR, risk ratio; PS, efficiency status. Similarly, individuals having a worse PS got a considerably shorter Operating-system. The median Operating-system in individuals having a PS of 0\1 and 2\4 was 17.4 and 4.0?weeks, respectively (Shape?1B). The Operating-system was considerably shorter in individuals in the PS 2\4 group than in the PS 0\1 group ( em P /em ? ?.001). Univariate (HR, 3.526; 95% CI, 2.641\4.709) and multivariate analyses (HR, 3.914; 95% CI, 2.908\5.269) revealed a PS of 2\4 was an unbiased factor predicting short OS (Desk?2B). To acquire further insight in to the effect of PS on ICI therapy result, we stratified individuals into 4 organizations according with their PS (PS 0, 1, 2, and 3\4) and undertook success analysis for every affected person group (Shape?2). The median PFS instances in individuals in the PS 0, 1, 2, and 3\4 organizations had been 6.9, 3.5, 2.3, and 1.1?weeks, respectively (Shape?2A). Furthermore, PFS was considerably shorter in individuals with PS 1, 2, and 3\4 than individuals with PS 0 (PS 1 vs PS 0: HR, 1.336; 95% CI, 1.031\1.732; em P /em ?=?.026; PS 2 vs PS 0: HR, 1.451; 95% CI, 1.214\1.734; em P /em ? ?.001; PS 3\4 vs PS 0: HR, 2.410; 95% CI, 1.772\3.277; em P /em ? ?.001). Likewise, Operating-system was considerably shorter in individuals with worse PS (Shape?2B). The median Operating-system times in individuals with PS 0, 1, 2, and 3\4 had been 20.4, 15.5, 5.0, and 1.9?weeks, respectively (PS 1 vs PS 0: HR, 1.536; 95% CI, 1.092\2.160; em P /em ?=?.014; PS 2 vs PS 0: HR, 2.088; 95% CI, 1.682\2.593; em P /em ? ?.001; PS 3\4 vs PS 0: HR, 4.619; 95% CI, 3.034\7.032, em P /em ? ?.001). Open up in another window Shape 2 A, Development\free success (PFS) of individuals with non\little\cell lung tumor treated with immune system checkpoint inhibitors with efficiency position (PS) 0 (solid range, n?=?103), PS 1 (dashed range, n?=?345), PS 2 (dotted range, n?=?64), or PS 3\4 (dashed and dotted range, n?=?15). B, General success (Operating-system) of individuals with PS 0 (solid range, n?=?103), PS 1 (dashed range, n?=?345), PS 2 (dotted range, n?=?64), or PS 3\4 (dashed and dotted range, n?=?15). CI, self-confidence period 3.3. Features of PS 2 individuals who benefited from ICI therapy Although individuals with PS 2 or more got worse success after ICI therapy than people that have PS significantly less than 2, some individuals with PS 2 taken care of immediately ICI treatment, attaining disease control for a lot more than 1?yr. In comparison, all individuals with PS 3\4 skilled disease development or death in under 10?weeks (Shape?2A). These observations claim that particular individuals with PS 2 could reap the benefits of ICI therapy, despite their poor PS. Therefore, we wanted to measure the features of individuals with PS 2 who benefited from ICI therapy. As the efficacies of pembrolizumab like a 1st\range treatment for NSCLC individuals with PD\L1 manifestation of 50% or more which of any ICIs as second\ or later on\line treatments regardless of PD\L1 manifestation in NSCLC individuals are very different, we stratified individuals relating to treatment technique and compared the final results of sufferers with PS 2 and PS 0\1 (Amount?S1). Cohort 1 included sufferers with NSCLC (PD\L1 appearance 50% or more) treated with pembrolizumab as initial\series treatment (Desk?S1), whereas cohort 2 included NSCLC sufferers with any PD\L1 appearance who had been treated with any ICI seeing that second\ or later on\series therapy (Desk?S2). Among sufferers with NSCLC with PD\L1 appearance of 50% or more who had been treated with pembrolizumab as initial\series therapy (cohort 1), the median PFS for sufferers with PS 2 was 7.3?a few months (95% CI, 1.5\11.4?a few months), whereas that of sufferers with PS 0\1 was 8.1?a few months (95% CI, 4.8?monthsCnot reached) (Amount?3A). There is no factor in PFS between sufferers with PS 2 and PS 0\1 ( em P /em ?=?.321). Nevertheless, sufferers with PS 3\4 acquired a PFS of just one 1.0?month (95% CI, 0.3?a few months\not reached) (Amount?3A), that was significantly worse than that of PS 0\1 sufferers ( em P /em ? ?.001). Very similar findings were noticed for the Operating-system (Amount?3B). The 1\calendar year Operating-system prices.These findings act like those of a retrospective research where nivolumab was presented with to 63 individuals, including 20 individuals with PS 2. higher, had been employed for our analyses. The development\free success (PFS) and general success (Operating-system) of sufferers with PS 2 or more were considerably shorter weighed against those of PS 0\1 sufferers (median PFS, 4.1 vs 2.0?a few months; valuetest. Aside from PS, BMI was the just clinical aspect that considerably differed between your groupings. 3.2. Functionality position 2 or better is connected with poor success in NSCLC sufferers treated with ICIs Sufferers with PS 0\1 acquired a significantly much longer PFS than sufferers with PS 2\4 (median PFS, 4.1 vs 2.0?a few months, respectively, valuevaluemutationPositive2.0091.509\2.673 .0011.5981.176\2.170.003WT or undetermined1.0001.000SmokingEx or current0.6150.483\0.783 .0010.6230.418\0.930.021Never1.0001.000PS2\41.8191.404\2.357 .0011.9081.465\2.484 .0010\11.0001.000Treatment series2nd series or later on1.6851.262\2.250 .0011.6901.258\2.270 .0011st line1.0001.000 (B) GenderFemale1.0500.786\1.403.7410.6380.384\1.063.084Male1.0001.000StagingIII or IV1.3771.046\1.813.0231.3631.033\1.798.029Recurrence1.0001.000 mutationPositive1.3560.958\1.918.0861.2030.821\1.764.344WT or undetermined1.0001.000SmokingEx or current0.7830.579\1.060.1130.5540.324\0.949.031Never1.0001.000PS2\43.5262.641\4.709 .0013.9142.908\5.269 .0010\11.0001.000Treatment series2nd series or later on1.4630.999\2.141.0501.5261.036\2.248.0331st line1.0001.000 Open up in another window Abbreviations: CI, confidence interval; EGFR, epidermal development aspect receptor; HR, threat ratio; PS, functionality status. Similarly, sufferers using a worse PS acquired a considerably shorter Operating-system. The median Operating-system in sufferers using a PS of 0\1 and 2\4 was 17.4 and 4.0?a few months, respectively (Amount?1B). The Operating-system was considerably shorter in sufferers in the PS 2\4 group than in the PS 0\1 group ( em P /em ? ?.001). Univariate (HR, 3.526; 95% CI, 2.641\4.709) and multivariate analyses (HR, 3.914; 95% CI, 2.908\5.269) revealed a PS of 2\4 was an unbiased factor predicting short OS (Desk?2B). To acquire further insight in to the influence of PS on ICI therapy final result, we stratified sufferers into 4 groupings according with their PS (PS 0, 1, 2, and 3\4) and undertook success analysis for every affected individual group (Amount?2). The median PFS situations in sufferers in the PS 0, 1, 2, and 3\4 groupings had been 6.9, 3.5, 2.3, and 1.1?a few months, respectively (Amount?2A). Furthermore, PFS was considerably shorter in sufferers with PS 1, 2, and 3\4 than sufferers with PS 0 (PS 1 vs PS 0: HR, 1.336; 95% CI, 1.031\1.732; em P /em ?=?.026; PS 2 vs PS 0: HR, 1.451; 95% CI, 1.214\1.734; em P /em ? ?.001; PS 3\4 vs PS 0: HR, 2.410; 95% CI, 1.772\3.277; em P /em ? ?.001). Likewise, Operating-system was considerably shorter in sufferers with worse PS (Amount?2B). The median Operating-system times in Rabbit Polyclonal to PLG sufferers with PS 0, 1, 2, and 3\4 had been 20.4, 15.5, 5.0, and 1.9?a few months, respectively (PS 1 vs PS 0: HR, 1.536; 95% CI, 1.092\2.160; em P /em ?=?.014; PS 2 vs PS 0: HR, 2.088; 95% CI, 1.682\2.593; em P /em ? ?.001; PS 3\4 vs PS 0: HR, 4.619; 95% CI, 3.034\7.032, em P /em ? ?.001). Open up in another window Amount 2 A, Development\free success (PFS) of sufferers with non\little\cell lung cancers treated with immune system checkpoint inhibitors with functionality position (PS) 0 (solid series, n?=?103), PS 1 (dashed series, n?=?345), PS 2 (dotted series, n?=?64), or PS 3\4 (dashed and dotted series, n?=?15). B, General success (Operating-system) of sufferers with PS 0 (solid series, n?=?103), PS 1 (dashed series, n?=?345), PS 2 (dotted series, n?=?64), or PS 3\4 (dashed and dotted series, n?=?15). CI, self-confidence interval 3.3. Characteristics of PS 2 patients who benefited from ICI therapy Although patients with PS 2 or higher had worse survival after ICI therapy than those with PS less than 2, some patients with PS 2 responded Begacestat (GSI-953) to ICI treatment, achieving disease control for more than 1?12 months. By contrast, all patients with PS 3\4 experienced disease progression or death in less than 10?months (Physique?2A). These observations suggest that certain patients with PS 2 could benefit from ICI therapy, despite their poor PS. Hence, we sought to assess the characteristics of patients with PS 2 who benefited from ICI therapy. Because the efficacies of pembrolizumab as a first\line treatment for NSCLC patients with PD\L1 expression of 50% or higher and that of any ICIs as second\ or later\line treatments irrespective of PD\L1 expression in NSCLC patients are quite different, we stratified patients according to treatment strategy and compared the outcomes of patients with PS 2 and PS 0\1 (Physique?S1). Cohort 1 included patients with NSCLC (PD\L1 expression 50% or higher) treated with pembrolizumab as first\line treatment (Table?S1), whereas cohort 2 included NSCLC patients with any PD\L1 expression who were treated with any ICI as second\ or later\line therapy (Table?S2). Among patients with NSCLC with PD\L1 expression of 50% or higher who were treated with pembrolizumab as first\line therapy (cohort 1), the median PFS for patients with PS 2 was 7.3?months.Nevertheless, it should be noted that this duration of treatment was shorter in patients with PS 2 than in those with PS 0\1 (Physique?2A), which could partly explain the lower frequency of AEs in patients with PS2. between the groups. 3.2. Performance status 2 or greater is associated with poor survival in NSCLC patients treated with ICIs Patients with PS 0\1 had a significantly longer PFS than patients with PS 2\4 (median PFS, 4.1 vs 2.0?months, respectively, valuevaluemutationPositive2.0091.509\2.673 .0011.5981.176\2.170.003WT or undetermined1.0001.000SmokingEx or current0.6150.483\0.783 .0010.6230.418\0.930.021Never1.0001.000PS2\41.8191.404\2.357 .0011.9081.465\2.484 .0010\11.0001.000Treatment line2nd line or later1.6851.262\2.250 .0011.6901.258\2.270 .0011st line1.0001.000 (B) GenderFemale1.0500.786\1.403.7410.6380.384\1.063.084Male1.0001.000StagingIII or IV1.3771.046\1.813.0231.3631.033\1.798.029Recurrence1.0001.000 mutationPositive1.3560.958\1.918.0861.2030.821\1.764.344WT or undetermined1.0001.000SmokingEx or current0.7830.579\1.060.1130.5540.324\0.949.031Never1.0001.000PS2\43.5262.641\4.709 .0013.9142.908\5.269 .0010\11.0001.000Treatment line2nd line or later1.4630.999\2.141.0501.5261.036\2.248.0331st line1.0001.000 Open in a separate window Abbreviations: CI, confidence interval; EGFR, epidermal growth factor receptor; HR, hazard ratio; PS, performance status. Similarly, patients with a worse PS had a significantly shorter OS. Begacestat (GSI-953) The median OS in patients with a PS of 0\1 and 2\4 was 17.4 and 4.0?months, respectively (Figure?1B). The OS was significantly shorter in patients in the PS 2\4 group than in the PS 0\1 group ( em P /em ? ?.001). Univariate (HR, 3.526; 95% CI, 2.641\4.709) and multivariate analyses (HR, 3.914; 95% CI, 2.908\5.269) revealed that a PS of 2\4 was an independent factor predicting short OS (Table?2B). To obtain further insight into the impact of PS on ICI therapy outcome, we stratified patients into 4 groups according to their PS (PS 0, 1, 2, and 3\4) and undertook survival analysis for each patient group (Figure?2). The median PFS times in patients in the PS 0, 1, 2, and 3\4 groups were 6.9, 3.5, 2.3, and 1.1?months, respectively (Figure?2A). Furthermore, PFS was significantly shorter in patients with PS 1, 2, and 3\4 than patients with PS 0 (PS 1 vs PS 0: HR, 1.336; 95% CI, 1.031\1.732; em P /em ?=?.026; PS 2 vs PS 0: HR, 1.451; 95% CI, 1.214\1.734; em P /em ? ?.001; PS 3\4 vs PS 0: HR, 2.410; 95% CI, 1.772\3.277; em P /em ? ?.001). Similarly, OS was significantly shorter in patients with worse PS (Figure?2B). The median OS times in patients with PS 0, 1, 2, and 3\4 were 20.4, 15.5, 5.0, and 1.9?months, respectively (PS 1 vs PS 0: HR, 1.536; 95% CI, 1.092\2.160; em P /em ?=?.014; PS 2 vs PS 0: HR, 2.088; 95% CI, 1.682\2.593; em P /em ? ?.001; PS 3\4 vs PS 0: HR, 4.619; 95% CI, 3.034\7.032, em P /em ? ?.001). Open in a separate window FIGURE 2 A, Progression\free survival (PFS) of patients with non\small\cell lung cancer treated with immune checkpoint inhibitors with performance status (PS) 0 (solid line, n?=?103), PS 1 (dashed line, n?=?345), PS 2 (dotted line, n?=?64), or PS 3\4 (dashed and dotted line, n?=?15). B, Overall survival (OS) of patients with PS 0 (solid line, n?=?103), PS 1 (dashed line, n?=?345), PS 2 (dotted line, n?=?64), or PS 3\4 (dashed and dotted line, n?=?15). CI, confidence interval 3.3. Characteristics of PS 2 patients who benefited from ICI therapy Although patients with PS 2 or higher had worse survival after ICI therapy than those with PS less than 2, some patients with PS 2 responded to ICI treatment, achieving disease control for more than 1?year. By contrast, all patients with PS 3\4 experienced disease progression or death in less than 10?months (Figure?2A). These observations suggest that certain patients with PS 2 could benefit from ICI therapy, despite their poor PS. Hence, we sought to assess the characteristics of patients with PS 2 who benefited from ICI therapy. Because the efficacies of pembrolizumab as a first\line treatment for NSCLC patients with PD\L1 expression of 50% or higher and that of any ICIs as second\ or later\line treatments irrespective of PD\L1 expression in NSCLC patients are quite different, we stratified patients according to treatment strategy and compared the outcomes of patients with PS 2 and PS 0\1 (Figure?S1). Cohort 1 included patients with NSCLC (PD\L1 expression 50% or higher) treated with pembrolizumab as first\line treatment (Table?S1), whereas cohort 2 included NSCLC patients with any PD\L1 expression who were treated with any ICI as second\ or later\line therapy (Table?S2). Among patients with NSCLC with PD\L1 expression of 50% or higher who were treated with pembrolizumab as first\line therapy (cohort 1), the median PFS for patients with PS 2 was 7.3?months (95% CI, 1.5\11.4?months), whereas that of patients with PS 0\1 was 8.1?months (95% CI, 4.8?monthsCnot reached) (Figure?3A). There was no significant difference in PFS between patients with PS 2 and PS 0\1 ( em P /em ?=?.321). However, patients with PS 3\4 had a PFS of 1 1.0?month (95% CI, 0.3?months\not reached) (Figure?3A), which was significantly worse than that of PS 0\1 patients ( em P /em ? ?.001). Similar findings were observed for the OS (Figure?3B). The 1\year OS rates in patients with PS 2 and those.