2019 ASCO Annual Meeting!
Session: Lung Cancer—Non-Small Cell Metastatic
Type: Poster Session
Time: Sunday June 2, 8:00 AM to 11:00 AM
Location: Hall A
Pembrolizumab alone or with chemotherapy for PD-L1 positive NSCLC: A network meta-analysis of randomized trials.
Metastatic Non-Small Cell Lung Cancer
Lung Cancer—Non-Small Cell Metastatic
2019 ASCO Annual Meeting
Poster Board Number:
Poster Session (Board #410)
J Clin Oncol 37, 2019 (suppl; abstr 9087)
Author(s): Mark Doherty, Seanthel Delos Santos, Amanda Putri Rahmadian, Louis Everest, Kelvin K. Chan; Sunnybrook Odette Cancer Centre, University of Toronto, Toronto, ON, Canada; Sunnybrook Research Institute, Toronto, ON, Canada; Odette Cancer Centre, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON, Canada; Sunnybrook Health Sciences Centre, Odette Cancer Centre, University of Toronto, Toronto, ON, Canada
Background: Pembrolizumab (P) has replaced chemotherapy (C) as first-line treatment for advanced non-small cell lung cancer (NSCLC) with tumor PD-L1 expression > / = 50%. Among PD-L1 unselected patients, P+C is superior to C alone. This network meta-analysis compared P alone with P+C in patients with > / = 50% PD-L1 positive NSCLC. Methods: An indirect network was constructed to compare P and P+C through the control arms of the Keynote 024, 189 and 407 (PD-L1 > / = 50% subgroup) trials. Baseline characteristics and chemotherapy outcomes were examined for heterogeneity. Overall survival (OS), progression-free survival (PFS), objective response rate (ORR) and toxicities including immune-related adverse events (irAE) were extracted from trial results. Toxicity results were unavailable for the PD-L1 > / = 50% subgroups of KN 189 & 407, so overall study results were used. Survival outcomes are expressed as hazard ratios (HRs) or restricted mean survival time (RMST) ratios, and toxicity and ORR as risk difference (RD). Results: 507 patients were included: 154 on P, 430 on C and 483 on P+C. Patient characteristics across trials were similar in age, sex, performance status and smoking history. All trials had similar chemotherapy outcomes (PFS 6, 4.9, 4.8 mos) suggesting similar populations. Network meta-analysis showed no difference between P+C and C alone in OS (HR 0.85, 95%CI 0.45-1.59, p = 0.60) or PFS (HR 0.73, 95%CI 0.48-1.1, p = 0.13), but P+C was associated with higher ORR (+16.9%, 95%CI 0.7-33%, p = 0.04). RMST analysis suggested fewer early PFS events with P+C (0-6 mo RMST ratio 1.25, RMST difference 1.02 mo, p = 0.002), with the difference disappearing at 1 year (0-12 mo RMST ratio 1.16, p = 0.07). No difference in RMST for OS was found. Overall toxicities, hematologic and grade 3-5 toxicities were higher with P+C compared with P alone (table). Conclusions: Among patients with > / = 50% PD-L1 positive NSCLC, P+C did not improve OS or PFS compared with P alone, but was associated with higher ORR. RMST analysis suggested fewer early progression events using P+C.
|All Grade Toxicities (P+C vs P)||Grade 3-5 Toxicities (P+C vs P)|
|RD (%)||95% CI||p||RD (%)||95% CI||p|
|Any||17.3||8.7, 25.8||< 0.01||23.3||4.7, 41.9||0.014|
|Led to Discontinuation||12||1.9, 22||0.02||7.4||0.5, 14.3||0.035|
|Neutropenia||25.9||17.2, 34.5||< 0.01||14.7||5.3, 24.1||0.002|
|Vomiting||20.5||12.2, 28.7||< 0.01||-0.8||-4.7, 3.1||0.69|
|Thrombocytopenia||16.5||9.6, 23.4||< 0.01||6||1.3, 107||0.012|
|Any irAE||-9.1||-25.8, 7.6||0.29||-3.1||-9.1, 2.8||0.30|
|Severe skin reaction||-3.2||-7.1, 0.7||0.11||-3.4||-6.7, -0.1||0.045|