Pembrolizumab Plus Research Articles

MA11.07 Pembrolizumab Plus Maintenance Olaparib as First-Line Therapy for Metastatic Nonsquamous NSCLC: Phase 3 KEYLYNK-006 Study

MA11.07 Pembrolizumab Plus Maintenance Olaparib as First-Line Therapy for Metastatic Nonsquamous NSCLC: Phase 3 KEYLYNK-006 Study

Neoadjuvant Pembrolizumab Plus Chemotherapy in Early-Stage Triple-Negative Breast Cancer: A Nationwide Retrospective Turkish Oncology Group Study

Background/Objectives: Following the results of the phase 3 KEYNOTE-522 trial, the U.S. Food and Drug Administration approved pembrolizumab, a humanized IgG4 kappa monoclonal antibody, in combination with neoadjuvant chemotherapy as a new standard of care for high-risk early-stage triple-negative breast cancer (TNBC). This retrospective, multicenter study in Türkiye assessed the real-world efficacy and safety of neoadjuvant pembrolizumab combined with chemotherapy in early-stage TNBC. Methods: The study included 108 patients treated between 2021 and 2023 across 14 oncology centers. Three distinct neoadjuvant regimens incorporating pembrolizumab were administered at the discretion of the treating physicians. The primary outcomes were the pathological complete response (pCR) rate after neoadjuvant therapy and the 2-year event-free survival (EFS) and overall survival (OS) rates. Results: The observed pCR rate was 63.9%, closely mirroring the 64.8% reported in the KEYNOTE-522 trial. At the two-year mark, the EFS rate was 87.2% and the OS rate was 92.3%. Multivariable analysis identified pCR as the sole independent predictor of both EFS and OS. The safety profile was consistent with previous clinical trial data, with most adverse events being of grade 1–2 in severity. Conclusions: These findings provide valuable real-world confirmation of the efficacy and safety of neoadjuvant pembrolizumab–chemotherapy in early-stage TNBC, complementing evidence from randomized trials.

Pembrolizumab With or Without Maintenance Olaparib for Metastatic Squamous Non-SCLC That Responded to First-Line Pembrolizumab Plus Chemotherapy

IntroductionPoly (adenosine diphosphate-ribose) polymerase inhibitors can up-regulate programmed death-ligand 1 expression and promote immune-mediated responses and may improve efficacy of first-line anti‒programmed cell death protein 1‒based therapies in patients with metastatic squamous NSCLC. MethodsIn this randomized, double-blind, phase 3 trial (NCT03976362), adults with previously untreated stage IV squamous NSCLC received 4 cycles of induction therapy (pembrolizumab 200 mg every 3 weeks plus carboplatin and paclitaxel or nab-paclitaxel). Patients with disease control were randomized to 31 cycles of pembrolizumab 200 mg every 3 weeks plus olaparib 300 mg orally twice daily or placebo. Dual primary end points were progression-free survival (PFS) and overall survival (OS). PFS was tested at interim analysis 2 (the final PFS analysis); OS was tested at final analysis. ResultsA total of 851 patients received induction treatment; 296 were randomized to pembrolizumab plus olaparib and 295 to pembrolizumab plus placebo. At interim analysis 2, with median follow-up of 27.1 months, median (95% confidence interval [CI]) PFS was 8.3 (6.7‒9.7) months in the pembrolizumab plus olaparib group and 5.4 (4.1‒5.6) months in the pembrolizumab plus placebo group (hazard ratio = 0.77, 95% CI: 0.63‒0.93, p = 0.0040 [not significant at a one sided at superiority boundary of p = 0.003]). At final analysis, with median follow-up of 33.4 months, median (95% CI) OS was 19.1 (15.9‒22.2) and 18.6 (16.0‒21.6) months, respectively (hazard ratio = 1.01, 95% CI: 0.83‒1.24, p = 0.5481). Treatment-related adverse events occurred in 76.5% and 65.1% of patients, respectively. ConclusionsAdding olaparib to pembrolizumab as maintenance therapy for metastatic squamous NSCLC did not significantly improve PFS versus pembrolizumab plus placebo, neither PFS nor OS met the prespecified statistical significance boundary. No new safety signals were identified. Trial registrationClinicalTrials.gov, NCT03976362.

P4.11E.02 Efficacy of Pembrolizumab Plus Pemetrexed in Older Patients with Non-squamous NSCLC According to PD-L1 Status from the CJLSG1901 Study

P4.11E.02 Efficacy of Pembrolizumab Plus Pemetrexed in Older Patients with Non-squamous NSCLC According to PD-L1 Status from the CJLSG1901 Study

Long-Term Temporal Trends of Real-World Healthcare Costs Associated with Nivolumab Plus Ipilimumab and Pembrolizumab Plus Axitinib as First-Line Treatment for Advanced or Metastatic Renal Cell Carcinoma.

Nivolumab plus ipilimumab (NIVO + IPI) and pembrolizumab plus axitinib (PEM + AXI) are first-line (1L) treatments for advanced or metastatic renal cell carcinoma (aRCC), although the long-term trends in their associated real-world healthcare costs are not well defined. We compared the real-world healthcare costs of patients with aRCC who received 1L NIVO + IPI or PEM + AXI over 24months. Adults with RCC and secondary malignancy who initiated 1L NIVO + IPI or PEM + AXI were identified in the Merative MarketScan Commercial and Medicare Supplemental Databases (01/01/2004 to 09/30/2021). All-cause and RCC-related healthcare costs (unadjusted and adjusted) were assessed per patient per month (PPPM) at 6-month intervals post-treatment initiation (index date) up to 24months, and differences between the NIVO + IPI and PEM + AXI cohorts were compared. Of 325 patients with aRCC, 219 received NIVO + IPI and 106 received PEM + AXI as the 1L treatment. According to patients' follow-up length, the analyses for months7-12 included 210 patients in the NIVO + IPI cohort and 103 in the PEM + AXI cohort; months13-18 included 119 and 48 patients, respectively; and months19-24 included 81 and 25 patients. PPPM unadjusted all-cause total costs were $46,348 for NIVO + IPI and $38,097 for PEM + AXI in months1-6; $26,840 versus $27,983, respectively, in months7-12; $22,899 versus $25,137 in months13-18; and $22,279 versus $27,947 in months19-24. PPPM unadjusted RCC-related costs were $44,059 for NIVO + IPI and $36,456 for PEM + AXI in months1-6; $25,144 versus $26,692, respectively, in months7-12; $21,645 versus $23,709 in months13-18; and $20,486 versus $25,515 in months19-24. PPPM costs declined more rapidly for patients receiving NIVO + IPI compared to those receiving PEM + AXI, resulting in significantly lower all-cause costs associated with NIVO + IPI during months19-24 (difference - $10,914 [95% confidence interval - $21,436, - $1091]) and RCC-related costs during months7-12 (- $4747 [(- $8929, - $512]) and 19-24 (- $10,261 [- $20,842, - $421]) after adjustment. Cost savings for NIVO + IPI versus PEM + AXI were driven by differences in drug costs which, after adjustment, were significantly lower in months7-12 (difference - $5555 [all-cause], - $5689 [RCC-related]); 13-18 (- $7217 and - $6870, respectively); and 19-24 (- $16,682 and - $16,125). Although the real-world PPPM healthcare costs of 1L NIVO + IPI were higher compared with PEM + AXI in the first 6months of treatment, the costs associated with NIVO + IPI rapidly declined thereafter, resulting in significantly lower costs vs. PEM + AXI from months7 to 24.

Pembrolizumab Plus Carboplatin and Paclitaxel as First-Line Therapy for Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma (KEYNOTE-B10): A Single-Arm Phase IV Trial.

Standard-of-care first-line treatment for recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC) is pembrolizumab plus platinum and fluorouracil (FU). However, FU is associated with potential challenges (continuous 4-day infusion, high administration costs, and cardiovascular and gastrointestinal toxicities), creating a clinical need for alternative chemotherapy combinations. We evaluated the efficacy and safety of first-line pembrolizumab plus carboplatin and paclitaxel for R/M HNSCC in the open-label, single-arm, phase IV KEYNOTE-B10 study (ClinicalTrials.gov identifier: NCT04489888). Eligible adults had previously untreated, histologically or cytologically confirmed R/M HNSCC regardless of PD-L1 status, measurable disease per RECIST v1.1 by blinded independent central review (BICR), and an Eastern Cooperative Oncology Group performance status of 0 or 1. Patients received pembrolizumab 200 mg intravenously once every 3 weeks for ≤35 cycles and carboplatin AUC 5 mg/mL/min intravenously once every 3 weeks for ≤6 cycles and investigator's choice of paclitaxel 100 mg/m2 on days 1 and 8 or 175 mg/m2 on day 1, intravenously once every 3 weeks. The primary end point was objective response rate per RECIST v1.1 by BICR. Between October 27, 2020, and April 29, 2022, 149 patients were screened and 101 received treatment. As of February 20, 2023, the median follow-up was 18.9 months (range, 9.1-27.0). At this final analysis, 49 (49%) of 101 patients had an objective response (95% CI, 38.4 to 58.7), including seven patients (7%) with a confirmed complete response. Of the 101 treated patients, grade 3-5 and serious treatment-related adverse events occurred in 76 (75%) and 27 (27%), respectively. There were no new safety signals. Pembrolizumab plus carboplatin and paclitaxel showed promising antitumor activity and a manageable safety profile in first-line R/M HNSCC, suggesting this combination may be an alternative option for this patient population.

PT33 Cost-Effectiveness of Cemiplimab Plus Chemotherapy Versus Pembrolizumab Plus Chemotherapy As the First-Line Treatment for Advanced Non-Small Cell Lung Cancer: A Preliminary Study

PT33 Cost-Effectiveness of Cemiplimab Plus Chemotherapy Versus Pembrolizumab Plus Chemotherapy As the First-Line Treatment for Advanced Non-Small Cell Lung Cancer: A Preliminary Study

Survival Impact of Inflammation-based Prognostic Scores in Metastatic or Unresectable Esophageal Cancer Treated With Pembrolizumab Plus Chemotherapy.

Pembrolizumab plus chemotherapy has been indicated as the first-line treatment for metastatic or unresectable locally advanced esophageal cancer. However, pretreatment biomarkers for predicting clinical outcomes remain unclear. We investigated the predictive value of inflammation-based prognostic scores in patients treated with pembrolizumab and chemotherapy. The Prognostic Nutritional Index (PNI), C-reactive protein/albumin ratio (CAR), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) were calculated before initial treatment in 65 eligible patients with metastatic or unresectable locally advanced esophageal cancer receiving pembrolizumab plus CF therapy, and the relationship between these biomarkers and clinical outcomes was analyzed. The objective response rate (ORR) and progression disease (PD) were observed in 51% and 21% of all patients. Patients with PNI<39 have significantly worse treatment responses than those with PNI≥39 (ORR; 28% vs. 60%, PD; 44% vs. 13%, P =0.020). Progression-free survival (PFS) is significantly associated with the PNI and CAR ( P <0.001 and P =0.004, respectively). Overall survival (OS) is associated with PNI, CAR, and PLR ( P <0.001, P =0.008, and P =0.018, respectively). The PNI cutoff value of 39 is identified as an independent factor for PFS (odds ratio=0.27, 95% CI: 0.18-0.81, P =0.012) and OS (odds ratio=0.22, 95% CI: 0.08-0.59, P =0.003). Patients with PNI<39 have significantly worse 6-month PFS and 1-year OS than those with PNI≥39 (27.8% vs. 66.7%, 27.2% vs. 81.1%, respectively). In conclusion, inflammation-based prognostic scores are associated with survival in patients treated with pembrolizumab plus CF therapy. Pretreatment PNI is a promising candidate for predicting treatment response and survival.

Weekly paclitaxel (P), carboplatin (CP) plus pembrolizumab (PMB) as first-line treatment of recurrent or metastatic (R/M) or locally very advanced (LVA) head and neck squamous cell carcinoma (HNSCC): A retrospective study in 39 patients (pts).

e18018 Background: Since the results of the KN-048 trial, the combination of platinum/5FU plus PMB has become the standard of care (SOC) for R/M HNSCC pts. The KN-B10 study shows that 5FU can be replaced by P with a favorable response rate and toxicity profile. Weekly use of P reduces hematologic toxicity and increases dose-intensity. Methods: We retrospectively reviewed all records of patients with R/M or LVA (T4b and/or N3b) HNSCC, ECOG-PS 0 to 2, PDL1 CPS ≥ 1, treated in first-line with weekly P (80 mg/m2) and CP (AUC 2: maximum total dose of 250 mg and systematic G-CSF at D3 and D4) for up to 12 infusions plus PMB every 3 weeks for up to 35 administrations. Results: From July 2020 to April 2023, 39 pts (median age 63 years, 74% male, 18% PS2) were treated. Primary tumors: oropharynx 44%, larynx 23%, hypopharynx 18% and oral cavity 15%. Disease setting: LVA 20%, local recurrence in irradiated area 54%, local recurrence and distant metastases 10% distant metastases only15%. With a median follow-up of 19 months (m), median Overall Survival (mOS) was 17.2 m (95%CI: 10.8-NR). 31/39 (79%) pts achieved an objective response (OR): 7 CR and 24 PR. For the 8 LVA pts, all achieved an OR, with a median Event Free Survival of 10 m (95%CI: 6.27-NR): the 4 progression-free pts (8.6 m+ to 25 m+) were treated with radiotherapy after neoadjuvant immuno-chemotherapy. For the 31 R/M pts, ECOG-PS was a significant prognostic factor of OS, mOS: 19.3 m (95%CI: 14.4-NR) for ECOG-PS 0-1 pts vs. 10.3 m (95%CI: 5.4-13.9) for ECOG-PS 2 pts (p = 0.02). For R/M pts, median Progression Free survival was 6.9 m (95%CI: 4.4-8.6) and the ORR was 74%, with a median duration of response of 6.5 m (95%CI: 3.13-8.56). Toxicity was manageable, with 20 (51%) pts experiencing at least one grade 3-4 adverse event: hematologic 18% (including one febrile neutropenia), infection 5%, neuropathy 8%, diarrhea 8%, infusion reaction 8%, electrolyte disturbances 8%, renal failure 3% and no toxic deaths. Conclusions: The combination of weekly P and CP plus PMB produces a high ORR and increased OS consistent with the results of the Frail-Immune study (J. Fayette ASCO 2023). This regimen deserves further consideration not only in the R/M setting, but also in the neoadjuvant setting for locally advanced patients.

SWOG S2302, PRAGMATICA-LUNG: A prospective randomized study of ramucirumab plus pembrolizumab (PR) versus standard of care (SOC) for participants previously treated with immunotherapy for stage IV or recurrent non-small cell lung cancer.

TPS8657 Background: Most patients (pts) with advanced non-small cell lung cancer (NSCLC) will receive treatment with immunotherapy and develop tumor resistance. Several trials investigating combination therapy have not shown benefit over chemotherapy. Additional therapeutic options are needed. Complex clinical trials increase barriers to enrollment. Pragmatic trial designs may overcome challenges with accrual and representativeness in the appropriate setting. S1800A was a randomized phase II trial within Lung-MAP that showed a statistically significant improvement in overall survival (OS) with PR versus SOC for pts with advanced NSCLC who had tumor progression on prior chemotherapy and immunotherapy (JCO 2023). As a follow-on, we designed a pragmatic, randomized, registration intent trial to validate OS results and enhance representative accrual reflecting real-world practice. Methods: S2302 is a registration-intent randomized trial for pts who previously received PD-(L)1 inhibitor therapy for at least 84 days and platinum-based therapy, stratified by immediate prior line of therapy including PD-(L)1 inhibition (yes/no) and PS (0/1 v. 2). Pts are randomized to PR or investigator’s choice SOC (recommended to be based on NCCN guidelines). The primary objective is to compare OS between the arms. The only secondary objective is to summarize serious and unexpected high-grade (Grade 3-4) treatment-related adverse events and all Grade 5 adverse events. The accrual goal is 700 pts based on a design with 85% power to detect a hazard ratio of 0.77, using a 1-sided 2.5% level log-rank test. Estimated accrual duration is 24 months. As of January 2024, 286 pts were randomized, and enrollment is ongoing. S2302 Pragmatica-Lung presents a novel and potentially practice-changing paradigm to conduct a study with a combination of FDA approved drugs with well-known safety profiles and limited toxicity overlap. There are no onerous radiology or specimen requirements, and SOC treatment is provided as per FDA-approved package inserts and institutional policies. The goal is to empower practicing clinicians to enroll pts they see every day by reducing the study barriers and burden of clinical trial participation. The resulting pts enrolled will be more representative than other registration-intent trials. This approach allows the trial to reach more patients and holds the potential to better inform the field across a more representative set of pts with broader impact. Clinical trial information: NCT05633602 .

Pembrolizumab Plus Chemotherapy for Metastatic NSCLC With Programmed Cell Death Ligand 1 Tumor Proportion Score Less Than 1%: Pooled Analysis of Outcomes After Five Years of Follow-Up

BackgroundWe report long-term outcomes from a pooled analysis of patients with previously untreated metastatic NSCLC with programmed cell death ligand 1 (PD-L1) tumor proportion score (TPS) less than 1% enrolled in phase III studies of pembrolizumab plus chemotherapy versus placebo plus chemotherapy. MethodsThis exploratory pooled analysis included individual patient data from the KEYNOTE-189 global (NCT02578680) and Japan extension (NCT03950674) studies of metastatic nonsquamous NSCLC without EGFR or ALK alterations and the KEYNOTE-407 global (NCT02775435) and People's Republic of China extension (NCT03875092) studies of metastatic squamous NSCLC. Patients received pembrolizumab or placebo plus pemetrexed and cisplatin or carboplatin in KEYNOTE-189 and pembrolizumab or placebo plus carboplatin and paclitaxel or nab-paclitaxel in KEYNOTE-407. PD-L1 TPS was centrally assessed using PD-L1 IHC 22C3 pharmDx (Agilent Technologies, Carpinteria, CA). ResultsOverall, 442 patients were included in this analysis (pembrolizumab plus chemotherapy, n = 255; chemotherapy, n = 187). The median follow-up was 60.7 (range, 49.9‒72.0) months. Pembrolizumab plus chemotherapy improved overall survival (hazard ratio, 0.64; 95% confidence interval [CI]: 0.51‒0.79) and progression-free survival (hazard ratio, 0.66; 95% CI: 0.54‒0.81) versus chemotherapy. The 5-year overall survival rates (95% CI) were 12.5% (8.6%‒17.3%) versus 9.3% (5.6%‒14.1%). Grades 3 to 5 treatment-related adverse events occurred in 59.1% of patients for pembrolizumab plus chemotherapy and 61.3% for chemotherapy. ConclusionWith approximately 5 years of follow-up, pembrolizumab plus chemotherapy provided clinically meaningful and durable improvements in survival outcomes versus chemotherapy alone in patients with previously untreated metastatic NSCLC with PD-L1 TPS less than 1%. These results continue to support pembrolizumab plus chemotherapy as a standard of care in this patient population.ClinicalTrials.gov, NCT02578680 (KEYNOTE-189 global), NCT03950674 (KEYNOTE-189 Japan extension), NCT02775435 (KEYNOTE-407 global), NCT03875092 (KEYNOTE-407 People's Republic of China extension).

Efficacy and Safety of First-line Pembrolizumab Plus Platinum and Pemetrexed in Elderly Patients with Non-squamous Non-small-cell Lung Cancer.

Objective Pembrolizumab plus platinum and pemetrexed (Pemb-Plt-PEM) combination therapy is an effective first-line treatment for advanced non-squamous non-small-cell lung cancer (NSCLC), regardless of programmed death ligand 1 expression. However, the effectiveness and feasibility of first-line Pemb-Plt-PEM therapy in elderly patients (≥75 years old) remain unclear. Therefore, this study investigated the safety and efficacy of first-line Pemb-Plt-PEM in elderly patients with nonsquamous NSCLC. Methods We retrospectively evaluated the data of patients ≥75 years old with non-squamous NSCLC who were treated with first-line Pemb-Plt-PEM from December 2018 to December 2020 at 10 institutes in Japan. Data on patient characteristics, efficacy of pemb-Plt-PEM therapy, and the type and severity of adverse events were reviewed. Results Thirty patients [20 men and 10 women; median age: 76 (range: 75-82) years old] were included in the analysis. The overall response rate, disease control rate, median progression-free survival (PFS), and median overall survival (OS) were 40.0%, 66.7%, and 7.5 and 24.0 months, respectively. The treatment-related deaths were caused by pneumonitis. First-line Pemb-Plt-PEM was associated with the PFS, based on the neutrophil-to-lymphocyte ratio (NLR). The PFS for low and high NLR values was 10.1 and 2.0 months, respectively. Furthermore, the sex and NLR influenced the association between Pemb-Plt-PEM and the OS. The OS for low and high NLR values was 32.8 and 2.6 months, respectively. Conclusion First-line pemb-Plt-PEM therapy is effective and feasible in elderly patients with non-squamous NSCLC.

A Case of Hypopharyngeal Carcinoma Long-term Success Achieved by Combination Therapy with Pembrolizumab Plus Chemotherapy After Failure of Pembrolizumab Monotherapy

A Case of Hypopharyngeal Carcinoma Long-term Success Achieved by Combination Therapy with Pembrolizumab Plus Chemotherapy After Failure of Pembrolizumab Monotherapy

Pembrolizumab Plus Chemotherapy Per PD-L1 Stratum In Patients With Metastatic Non–Small Cell Lung Cancer: Real-World Effectiveness Versus Trial Efficacy

BackgroundClinical trial efficacy and real-world effectiveness of oncological treatments can differ. This study assessed the real-world survival outcomes of first-line pembrolizumab plus chemotherapy per PD-L1 stratum in patients with metastatic non–small cell lung cancer (mNSCLC) and compared them to clinical trial results. Patients and MethodsAll patients with nonsquamous and squamous mNSCLC who received first-line pembrolizumab plus chemotherapy in 7 Dutch teaching hospitals between January 1, 2019 and December 31, 2021 were included. Hazard ratios (HR) with confidence intervals (95% CI) for overall survival (OS) and progression-free survival (PFS) were estimated to determine the efficacy-effectiveness gap (EE gap) between real-world and clinical trial, stratified by PD-L1 stratum. ResultsThe nonsquamous cohort (n = 486) consisted of 269 patients with PD-L1 < 1%, 158 with PD-L1 1% to 49%, and 59 with PD-L1 ≥ 50%. The squamous cohort (n = 117) consisted of 70 patients with PD-L1 < 1% and 47 with PD-L1 ≥ 1%. For OS, an EE gap was observed in nonsquamous patients with PD-L1 < 1% (HR 1.38 (95% CI 1.06-1.78; median OS 10 vs. 17.2 months) and HRs consistently >1 in all other nonsquamous and squamous PD-L1 strata, although not statistically significant. No EE-gap for PFS was observed in any stratum. ConclusionNo significant EE gap was found for pembrolizumab plus chemotherapy, except in the stratum nonsquamous mNSCLC with <1% PD-L1 tumor expression. In these patients, the survival in real-world was considerably shorter compared to the clinical trial results. Further studies are needed to determine which patient, treatment and or context factors contribute to this disparity.

EE524 Cost-Effectiveness of Neoadjuvant Pembrolizumab Plus Chemotherapy Followed by Adjuvant Pembrolizumab for High-Risk Early-Stage Triple Negative Breast Cancer in Costa Rica

EE524 Cost-Effectiveness of Neoadjuvant Pembrolizumab Plus Chemotherapy Followed by Adjuvant Pembrolizumab for High-Risk Early-Stage Triple Negative Breast Cancer in Costa Rica

EE62 Cost-Effectiveness of Neoadjuvant Pembrolizumab Plus Chemotherapy Followed By Adjuvant Pembrolizumab for High-Risk Early-Stage Triple-Negative Breast Cancer (ETNBC) in France

EE62 Cost-Effectiveness of Neoadjuvant Pembrolizumab Plus Chemotherapy Followed By Adjuvant Pembrolizumab for High-Risk Early-Stage Triple-Negative Breast Cancer (ETNBC) in France

PT33 Cost-Effectiveness of Pembrolizumab Plus Chemotherapy, With or Without Bevacizumab for the First-Line Treatment of PD-L1-Positive Patients With Persistent, Recurrent, or Metastatic Cervical Cancer in France

PT33 Cost-Effectiveness of Pembrolizumab Plus Chemotherapy, With or Without Bevacizumab for the First-Line Treatment of PD-L1-Positive Patients With Persistent, Recurrent, or Metastatic Cervical Cancer in France

EE210 Cost-Effectiveness Analysis of Pembrolizumab Plus Chemotherapy as Neoadjuvant Therapy and Continued as a Single Agent as Adjuvant Therapy for High-Risk Early-Stage Triple-Negative Breast Cancer in Greece

EE210 Cost-Effectiveness Analysis of Pembrolizumab Plus Chemotherapy as Neoadjuvant Therapy and Continued as a Single Agent as Adjuvant Therapy for High-Risk Early-Stage Triple-Negative Breast Cancer in Greece

Pembrolizumab Plus Chemotherapy Followed by Pembrolizumab in Patients With Early Triple-Negative Breast Cancer

In the phase 3 KEYNOTE-522 study, addition of pembrolizumab to neoadjuvant chemotherapy followed by adjuvant pembrolizumab significantly increased pathologic complete response (pCR) and event-free survival (EFS) vs neoadjuvant chemotherapy in patients with early triple-negative breast cancer. To evaluate efficacy and safety outcomes for patients enrolled in East/Southeast Asia (Asia) in KEYNOTE-522. KEYNOTE-522, a multicenter, double-blind, randomized clinical trial, enrolled 1174 patients between March 7, 2017, and September 13, 2018. For interim EFS and overall survival (OS) analyses (data cutoff, March 23, 2021), median follow-up was 39.8 months (range, 30.4-46.9 months) for pembrolizumab plus chemotherapy and 40.8 months (range, 30.1-46.9 months) for placebo plus chemotherapy. Data cutoff for pCR analysis was September 24, 2018. This secondary analysis included adults enrolled in Asia with newly diagnosed, previously untreated, nonmetastatic triple-negative breast cancer (tumor stage T1c and nodal stage N1-2 or tumor stage T2-4 and nodal stage N0-2) and Eastern Cooperative Oncology Group performance status of 0 to 1, regardless of programmed cell death ligand 1 (PD-L1) status. Patients were randomized 2:1 to 4 cycles of pembrolizumab (200 mg every 3 weeks) or placebo plus carboplatin and paclitaxel and another 4 cycles of pembrolizumab or placebo plus doxorubicin or epirubicin and cyclophosphamide before surgery. After definitive surgery, patients received pembrolizumab or placebo every 3 weeks for 9 cycles or until recurrence or unacceptable toxic effects. The main outcome was pCR (no evidence of primary tumor after neoadjuvant therapy or carcinoma in situ after neoadjuvant therapy and no regional lymph node involvement after neoadjuvant therapy) at the time of definitive surgery and EFS. A total of 216 of 1174 randomized patients (all female; median [range] age, 46.0 [24.0-71.0] years) were from Korea, Japan, Taiwan, and Singapore (136 in the pembrolizumab plus chemotherapy group and 80 in the placebo plus chemotherapy group). Of these patients, 104 (76.5%) in the pembrolizumab plus chemotherapy group and 60 (75.0%) in the placebo plus chemotherapy group had a tumor PD-L1 combined positive score of 1 or greater. Pathologic complete response was 58.7% (95% CI, 46.7%-69.9%) with pembrolizumab plus chemotherapy and 40.0% (95% CI, 26.4%-54.8%) with placebo plus chemotherapy; benefit was observed regardless of PD-L1 status. Thirteen patients (9.6%) in the pembrolizumab plus chemotherapy group and 20 patients (25.0%) in the placebo plus chemotherapy group had EFS events (hazard ratio, 0.35; 95% CI, 0.17-0.71). The 36-month EFS rate was 91.2% (95% CI, 85.0%-94.9%) with pembrolizumab plus chemotherapy and 77.2% (95% CI, 66.3%-85.0%) with placebo plus chemotherapy. Grade 3 to 4 treatment-related adverse events occurred in 109 patients (80.1%) receiving pembrolizumab plus chemotherapy and 64 patients (81.0%) receiving placebo plus chemotherapy. In this subgroup analysis of patients enrolled in Asia in KEYNOTE-522, neoadjuvant pembrolizumab plus chemotherapy followed by adjuvant pembrolizumab led to clinically meaningful improvements in pCR and EFS vs neoadjuvant chemotherapy alone. These findings support the use of neoadjuvant pembrolizumab plus chemotherapy followed by adjuvant pembrolizumab as a standard-of-care therapy for patients in Asian countries with early triple-negative breast cancer. ClinicalTrials.gov Identifier: NCT03036488.

305P A real-world multicenter cohort study of lenvatinib (LEN) plus pembrolizumab (PEM) in Japanese patients with endometrial cancer: Interim analysis of GOGO-EM4 study

305P A real-world multicenter cohort study of lenvatinib (LEN) plus pembrolizumab (PEM) in Japanese patients with endometrial cancer: Interim analysis of GOGO-EM4 study