Characteristics of Real-World Metastatic Non-Small Cell Lung Cancer Patients Treated with Nivolumab and Pembrolizumab During the Year Following Approval

Khozin, Sean; Abernethy, Amy Pickar; Nussbaum, Nathan; Zhi, Jizu; Curtis, Melissa D.; Tucker, Melisa; Lee, Shannon E.; Light, David E.; Gossai, Anala; Sorg, Rachael; Torres, Aracelis Z.; Patel, Prusha; Blumenthal, Gideon M.; Pazdur, Richard

doi:10.1634/theoncologist.2017-0353

Cited by 89 publications

(100 citation statements)

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“…This retrospective study analyzed outcomes in a large, longitudinal cohort of real‐world patients with advNSCLC who received treatment with PD‐(L)1 inhibitors before July 1, 2017. This study expands our prior description of early real‐world use of PD‐(L)1 inhibitors among patients with metastatic NSCLC and survival (cohort size nearly quadrupled, and observation time doubled), and it adds assessments of real‐world intermediate endpoints (rwPFS, rwTTP, rwTTNT, and rwTTD).…”

Section: Discussionmentioning

confidence: 99%

“…This study expands our prior investigation of real‐world patients with advNSCLC who received treatment with nivolumab or pembrolizumab (both PD‐1 inhibitors), conducted during the early adoption period after the initial approval in advNSCLC (both as the second or higher therapy line; nivolumab for patients with squamous histology tumors, and pembrolizumab for patients with PD‐L1–expressing tumors) . Since that study, 1) 4 additional approvals in advNSCLC have been granted to 3 different anti‐PD‐(L)1 therapies; 2) the number of patients treated with PD‐(L)1 inhibitors and the follow‐up period have substantially increased; 3) scientific understanding of PD‐L1 testing has matured; 4) management has changed, including the practice of treating beyond RECIST‐defined progression based on the continued benefit observed in some cases after early “pseudoprogression” because of inflammatory response; and 5) recognition of the importance of progression and treatment‐based intermediate endpoints for patients has grown .…”

Section: Introductionmentioning

confidence: 99%

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Real‐world progression, treatment, and survival outcomes during rapid adoption of immunotherapy for advanced non–small cell lung cancer

Khozin

Miksad

Adami

et al. 2019

Cancer

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110

144

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BackgroundDespite the rapid adoption of immunotherapies in advanced non–small cell lung cancer (advNSCLC), knowledge gaps remain about their real‐world (rw) performance.MethodsThis retrospective, observational, multicenter analysis used the Flatiron Health deidentified electronic health record‐derived database of rw patients with advNSCLC who received treatment with PD‐1 and/or PD‐L1 (PD‐[L]1) inhibitors before July 1, 2017 (N = 5257) and had ≥6 months of follow‐up. The authors investigated PD‐(L)1 line of treatment and PD‐L1 testing rates and the relationship between overall survival (OS) and rw intermediate endpoints: progression‐free survival (rwPFS), rw time to progression (rwTTP), rw time to next treatment (rwTTNT), and rw time to discontinuation (rwTTD).ResultsFirst‐line PD‐(L)1 inhibitor use increased from 0% (in the third quarter of 2014 [Q3 2014]) to 42% (Q2 2017) over the study period. PD‐L1 testing also increased (from 3% in Q3 2015 to 70% in Q2 2017). The estimated median OS was 9.3 months (95% CI, 8.9‐9.8 months), and the estimated rwPFS was 3.2 months (95% CI, 3.1‐3.3 months). Longer OS and rwPFS were associated with ≥50% PD‐L1 percentage staining results. Correlations (⍴) between OS and intermediate endpoints were ⍴ = 0.75 (95% CI, 0.73‐0.76) for rwPFS and ⍴ = 0.60 (95% CI, 0.57‐0.63) for rwTTP, and, for treatment‐based intermediate endpoints, correlations were ⍴ = 0.60 (95% CI, 0.56‐0.64) for rwTTNT (N = 856) and ⍴ = 0.81 (95% CI, 0.80‐0.82) for rwTTD.ConclusionsThe use of first‐line PD‐(L)1 inhibitors and PD‐L1 testing has substantially increased, with better outcomes for patients who have ≥50% PD‐L1 percentage staining. Intermediate rw tumor‐dynamics estimates were moderately correlated with OS in patients with advNSCLC who received immunotherapy, highlighting the need for optimizing and standardizing rw endpoints to enhance the understanding of patient outcomes outside clinical trials.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Real‐world progression, treatment, and survival outcomes during rapid adoption of immunotherapy for advanced non–small cell lung cancer

Khozin

Miksad

Adami

et al. 2019

Cancer

Self Cite

110

144

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“…The cohort comprised patients from the Flatiron Health network with mNSCLC who received nivolumab or pembrolizumab in the metastatic setting between January 1, 2011, and March 31, 2016 (Fig. ) .…”

Section: Methodsmentioning

confidence: 99%

Real-World Outcomes of Patients with Metastatic Non-Small Cell Lung Cancer Treated with Programmed Cell Death Protein 1 Inhibitors in the Year Following U.S. Regulatory Approval

et al. 2018

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Background Evidence from cancer clinical trials has strong internal validity but can be difficult to generalize to real‐world patient populations. Here we analyzed real‐world outcomes of patients with metastatic non‐small cell lung cancer (mNSCLC) treated with programmed cell death protein 1 (PD‐1) inhibitors in the first year following U.S. regulatory approval. Materials and Methods This retrospective study leveraged electronic health record (EHR) data collected during routine patient care in community cancer care clinics. The cohort included patients with mNSCLC who had received nivolumab or pembrolizumab for metastatic disease (n = 1,344) with >1 EHR‐documented visit from January 1, 2011, to March 31, 2016. Patients with a > 90‐day gap between advanced disease diagnosis and first EHR structured data entry were excluded. Results Estimated median overall survival (OS) was 8.0 months (95% confidence interval 7.4–9.0 months). Estimated median OS was 4.7 months (3.4–6.6) for patients with anaplastic lymphoma kinase rearrangement‐ and epidermal growth factor receptor mutation‐positive tumors, and 8.6 months (7.7–10.6) for patients without such mutations. Age at PD‐1 inhibitor initiation or line of therapy did not impact OS. Conclusion This analysis suggests OS in real‐world patients may be shorter than in conventional clinical trial patient cohorts, potentially due to narrow trial eligibility criteria. The lack of difference in OS by line of therapy or age at immunotherapy initiation suggests sustained benefit of PD‐1 inhibitors in multitreated patients with mNSCLC and that age is not a predictor of outcome. Further studies are underway in patients with comorbidities, organ dysfunction, and multiple prior therapies. Implications for Practice This study evaluated data derived from electronic health records of patients with metastatic non‐small cell lung cancer treated with programmed cell death protein 1 (PD‐1) inhibitors in the year following regulatory approval. This real‐world cohort had shorter overall survival (OS) indexed to PD‐1 inhibitor initiation than reported in clinical trials. Late‐line treatment did not influence OS, and patients aged >75 at immunotherapy initiation did not have worse outcomes than younger patients. As new therapies enter clinical practice, real‐world data can complement clinical trial evidence providing information on generalizability and helping inform clinical treatment decisions.

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“…The scale ranges from 0 to 5 (0: fully active; 1: restricted in physically strenuous activity; 2: up and about >50% of walking hours; 3: confined to bed or chair >50% of waking hours; 4: completely disabled; and 5: dead). Those with ECOG PS of 2 or higher are frequently excluded from clinical trials evaluating ICIs, even though more than 20% of such patients are treated with ICIs in real‐world practice . The number of older patients with cancer and ECOG PS of 2 or higher treated with ICIs in real‐world practice may be as high as 30% if not higher …”

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confidence: 99%

Immune Checkpoint Inhibitors in Real‐World Treatment of Older Adults with Non–Small Cell Lung Cancer

Muchnik

Loh

Strawderman

et al. 2019

J American Geriatrics Society

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OBJECTIVE To evaluate the efficacy and toxicity of immune checkpoint inhibitors (ICIs) in older patients with advanced non–small cell lung cancer (NSCLC) seen in routine clinical practice. DESIGN Retrospective study. SETTING Single academic institution and its affiliated centers. PARTICIPANTS Patients 70 years or older with advanced‐stage NSCLC seen between April 1, 2015, and April 1, 2017, and treated with ICIs. MEASUREMENTS Efficacy data included overall survival (OS) and time to treatment failure (TTF), stratified by age, comorbidities (Charlson Comorbidity Index [CCI]), and Eastern Cooperative Oncology Group Performance Status (ECOG PS), and estimated using the Kaplan‐Meier method and log‐rank test. Toxicity data included immune‐related adverse events (irAEs), need for glucocorticoids, and hospitalization. The associations of toxicity with age, CCI, and ECOG PS were evaluated using the exact χ2 test or Fisher exact test. RESULTS We included 75 patients (median age: 74 y; range, 70‐92 y); 53% had a CCI of 3 or higher; 49% had ECOG PS of 2 or higher. Median OS for the whole cohort was 8.2 months (ECOG PS 0‐1 vs ≥2: 13.7 vs 3.8 mo; p < .01). Median TTF was 4.2 months (ECOG PS 0‐1 vs ≥2: 5.6 vs 2.0 mo; p = .02). Overall, 37% of patients experienced irAE of any grade (a total of 37 events); 8% were grade 3 or higher (no ICI‐related deaths). Of those who discontinued ICIs (N = 64), 15% were due to irAEs. Of those who experienced irAEs, 64% required glucocorticoids. Hospitalizations during ICI treatment occurred in 72%. Toxicity generally did not differ by age, CCI, or ECOG PS. CONCLUSIONS Outcomes in our cohort were driven by ECOG PS rather than chronological age or comorbidities. The relatively high rates of ICI discontinuation, use of glucocorticoids, and hospitalization during ICI treatment in our study highlight the vulnerability of older adults with advanced NSCLC even in the immunotherapy era. J Am Geriatr Soc 67:905–912, 2019.

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Characteristics of Real-World Metastatic Non-Small Cell Lung Cancer Patients Treated with Nivolumab and Pembrolizumab During the Year Following Approval

Cited by 89 publications

References 11 publications

Real‐world progression, treatment, and survival outcomes during rapid adoption of immunotherapy for advanced non–small cell lung cancer

Real‐world progression, treatment, and survival outcomes during rapid adoption of immunotherapy for advanced non–small cell lung cancer

Real-World Outcomes of Patients with Metastatic Non-Small Cell Lung Cancer Treated with Programmed Cell Death Protein 1 Inhibitors in the Year Following U.S. Regulatory Approval

Immune Checkpoint Inhibitors in Real‐World Treatment of Older Adults with Non–Small Cell Lung Cancer

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