Keytruda as monotherapy is indicated for the first line treatment of metastatic non small cell lung carcinoma in adults whose tumours express PD L1 with a ≥ 50% tumour proportion score (TPS) with no EGFR or ALK positive tumour mutations.

KEYTRUDA is a programmed death receptor-1 (PD-1)-blocking antibody indicated:...as a single agent for the first-line treatment of patients with NSCLC expressing PD-L1 [Tumor Proportion Score (TPS) ≥1%] as determined by an FDA-approved test, with no EGFR or ALK genomic tumor aberrations, and is:...stage III where patients are not candidates for surgical resection or definitive chemoradiation, or...metastatic....as a single agent for the treatment of patients with metastatic NSCLC whose tumors express PD-L1 (TPS ≥1%) as determined by an FDA-approved test, with disease progression on or after platinum-containing chemotherapy.

PD-L1 expression positive (≥1%-49%)…Adenocarcinoma, large cell, NSCLC NOS…Preferred…(Carboplatin or cisplatin) + pemetrexed + Pembrolizumab (category 1)

For patients with negative (0%) and low positive PD-L1 expression (TPS 1% to 49%), non-SCC, and PS 0 to 1, and who are eligible for chemotherapy and pembrolizumab, clinicians should offer pembrolizumab/carboplatin/pemetrexed…

Similar to the global KEYNOTE-042 study, after 5 y of follow-up, pembro continued to demonstrate improved OS vs chemo with manageable safety in Chinese pts with previously untreated advanced or metastatic NSCLC without EGFR/ALK alterations with PD-L1 TPS ≥1%.

First-line pembrolizumab monotherapy continued to show durable clinical benefit versus chemotherapy after 5 years of follow-up in PD-L1–positive, locally advanced/metastatic NSCLC...

Pts had pathologically confirmed, completely resected stage IB (T ≥4 cm) to IIIA NSCLC of any PD-L1 expression...Pembrolizumab generally improved DFS versus placebo regardless of type of surgery, lymph node involvement, tumor size, and type and extent of adjuvant chemotherapy in pts with completely resected stage IB (T ≥4 cm) to IIIA NSCLC.

With 5 years of follow-up, first-line pembrolizumab monotherapy continued to show substantial clinical benefit with higher 5-year OS rates, and durable response over chemotherapy in patients with PD-L1–positive, locally advanced/metastatic NSCLC.

Pembrolizumab improved overall survival versus chemotherapy in patients with or without baseline brain metastases: benefit was seen in patients with PD-L1 TPS ≥50% (0.67 [95% confidence intervals (CI): 0.44‒1.02] and 0.66 [95% CI: 0.58‒0.76], respectively) and PD-L1 TPS ≥1% (0.83 [95% CI: 0.62‒1.10] and 0.78 [95% CI: 0.71‒0.85], respectively). Progression-free survival was improved, objective response rates were higher, and duration of response was longer with pembrolizumab versus chemotherapy regardless of brain metastasis status. 

With long-term follow-up, first-line pembrolizumab monotherapy continued to show improved OS, ORR and PFS-2 outcomes compared with platinum-based chemotherapy in patients with locally advanced/metastatic PD-L1–positive NSCLC without sensitizing EGFR/ALK alterations...

With more than 5 years of follow-up, pembrolizumab continued to provide clinically meaningful improvement in OS and PFS versus docetaxel in patients with previously treated, PD-L1–positive advanced NSCLC; 5-year OS rates were more than doubled in pembrolizumab-treated patients.

Overall ICI in combination improved survival across PD-L1 expression level subgroups compared with chemotherapy (platinum doublets +/- bevacizumab). Indirect comparisons of ICIs in combination therapy for first-line treatment in advanced non-squamous NSCLC showed little evidence of differences between pembrolizumab or atezolizumab in combination with chemotherapy and nivolumab/ipilimumab. 

...findings of this exploratory analysis suggest pembrolizumab monotherapy should be considered a standard first-line treatment option for advanced PD-L1 positive NSCLC regardless of STK11 or KEAP1 status.

Pembrolizumab continued to improve OS over docetaxel in the PD-L1 TPS ≥ 50% and ≥ 1% groups (hazard ratio [HR], 0.53; 95% CI, 0.42 to 0.66; P < .00001; and HR, 0.69; 95% CI, 0.60 to 0.80; P < .00001, respectively) after a 42.6-month (range, 35.2-53.2 months) median follow-up. Estimated 36-month OS rates were 34.5% versus 12.7% and 22.9% versus 11.0%, respectively.

We investigated overall survival after treatment with pembrolizumab monotherapy in patients with a PD-L1 TPS of 1% or greater....The median surival values by TPS population were 20·0 months (95% CI 15·4-24·9) for pembrolizumab versus 12·2 months (10·4-14·2) for chemotherapy, 17·7 months (15·3-22·1) versus 13·0 months (11·6-15·3), and 16·7 months (13·9-19·7) versus 12·1 months (11·3-13·3), respectively.

This randomised, open-label, phase 3 study was done in 213 medical centres in 32 countries….Overall survival was significantly longer in the pembrolizumab group than in the chemotherapy group in all three TPS populations (≥50% hazard ratio 0·69, 95% CI 0·56–0·85, p=0·0003; ≥20% 0·77, 0·64–0·92, p=0·0020, and ≥1% 0·81, 0·71–0·93, p=0·0018).

While the pembrolizumab/chemotherapy combination was the most effective therapy in the overall cohort of all-comers, treatment preferences varied by treatment-line setting, tumor characteristics, and outcome of interest. In the first-line setting, the most effective treatments for patients with PD-L1 expressions of ≥50%, 1-49%, and <1% were atezolizumab, pembrolizumab/chemotherapy, and nivolumab/ipilimumab, respectively.

In patients with advanced NSCLC and PD-L1 expression on at least 50% of tumor cells, pembrolizumab was associated with significantly longer progression-free and overall survival and with fewer adverse events than was platinum-based chemotherapy.

...Histologically- or cytologically-confirmed diagnosis of NSCLC that is anti-programmed cell death ligand 1 (PD-L1) positive per central laboratory review...

We included patients 70 years old and older with histological or cytological documented stage IIIB or IV aNSCLC and PD-L1 expression ≥ 1%....The estimated OS at one year was 61.7% (95% CI: 49.6-71.8%) and the median OS of our cohort was 19.2 months (95% CI: 11.3-25.5)....Our results support treating older adults with aNSCLC expressing PD-L1 with pembrolizumab in monotherapy.

Biological response modifiers (immunotherapy) resulted in significantly longer median progression-free survival in PD-L1-positive breast cancer (7.5 months compared to 5.0 months in control group)... higher complete responses in multiple myeloma (79% and 66% in the elotuzumab and control groups, respectively) and lower disease progression in PD-L1-positive non-small-cell lung cancer (62.1% of pembrolizumab versus 50.3% of chemotherapy patients had no disease progression at 6 months).

In this prospective observational study, PS-2 and elderly NSCLC patients with PD-L1 tumor proportion score (TPS) ≥1% who received first-line pembrolizumab monotherapy...Pembrolizumab monotherapy was relatively effective and tolerable as a first-line treatment for patients with PD-L1-positive advanced NSCLC who had poor PS or were elderly.

In 46 response-evaluable patients across cohorts, the ORR was 39% (9 confirmed partial responses [PRs] and 9 ongoing PRs, pending confirmation), and the disease control rate (DCR) was 82.6%. In 16 response-evaluable first-line patients, the ORR was 69% (5 confirmed PRs and 6 ongoing PRs, pending confirmation), and the DCR was 100%.Dato-DXd with pembrolizumab, ± platinum chemotherapy, demonstrates a tolerable safety profile and has notable activity in frontline and relapsed/refractory settings.

The median PFS was 2.9 mo (95%CI 1.8 - 5.6) and the median OS was 12.1 mo (95%CI 8.7 - 17.1). The ORR was 24.1% (2 complete and 12 partial responses), DCR was 53.4% and median DoR was 14.5 mo (95%CI 6.4 - 24.9)….This trial confirmed that pembrolizumab as first-line single agent is safe and active also in a subgroup of aNSCLC patients with PD-L1 < 50%.

Median follow up and PFS were 26.4 and 2.9 months, respectively….To the best of our knowledge, this is the first prospective trial in NSCLC with PD-L1 < 50% performed with a multiomic approach able to identify immune cell subsets and expression levels of genes associated to PFS under first line treatment with pembrolizumab.

For patients with tumor PD-(L)1 expression less than 50%, there was also a statistically significant real-world overall survival benefit for those who received treatment either with combination pembrolizumab plus chemotherapy (adjusted HR = 0.39, 95% CI = 0.32 to 0.46) or pembrolizumab monotherapy (adjusted HR = 0.55, 95% CI = 0.41 to 0.70) compared with patients receiving no documented treatment.

For patients with tumor PD-(L)1 expression less than 50%, there was also a statistically significant real-world overall survival benefit for those who received treatment either with combination pembrolizumab plus chemotherapy (adjusted HR = 0.39, 95% CI = 0.32 to 0.46) or pembrolizumab monotherapy (adjusted HR = 0.55, 95% CI = 0.41 to 0.70) compared with patients receiving no documented treatment.

We collected data of 136 elderly patients with advanced NSCLC who were treated with pembrolizumab plus chemotherapy or chemotherapy monotherapy....Subgroup analysis showed patients with positive PD-L1 expression, stage IV, good performance score (ECOG-PS <2), fewer comorbidities (simplified comorbidity score <9) or female patients had demonstrated a more evident OS benefit in pembrolizumab plus chemotherapy....Elderly patients using pembrolizumab plus chemotherapy achieved longer PFS and OS, but were more likely to discontinue due to adverse effects, so disease stage, PD-L1 expression, ECOG-PS and comorbidities should be considered when selecting first-line treatment.

Median OS was 26.3 months (95% CI, 18.3 to 40.4) for pembrolizumab and 13.4 months (9.4-18.3) for chemotherapy (hazard ratio, 0.62; 95% CI, 0.48 to 0.81). Kaplan-Meier estimates of the 5-year OS rate were 31.9% for the pembrolizumab group and 16.3% for the chemotherapy group....Pembrolizumab provides a durable, clinically meaningful long-term OS benefit versus chemotherapy as first-line therapy for metastatic NSCLC with PD-L1 tumor proportion score of at least 50%.

Patients with nonsquamous NSCLC were eligible...Patients in cohort A received 1 cycle of carboplatin...paclitaxel...and pembrolizumab...Patients in cohort B had nonsquamous NSCLC and received 3 cycles of cisplatin (75 mg/m2) and pemetrexed (500 mg/m2) plus pembrolizumab...In subgroup analyses in cohort A, ORR was achieved in 14 patients (66.7%) with PD-L1 TPS less than 1% and 50 (75.8%) with PD-L1 TPS 1% or greater... In cohort B, ORR was achieved in 20 patients (71.4%) with PD-L1 TPS less than 1% and in 29 (72.5%) with PD-L1 TPS 1% or greater...

Patients were randomized to pembrolizumab 2 mg/kg or 10 mg/kg Q3W, or docetaxel 75 mg/m2 Q3W for up to 35 cycles (2 years)...Median study follow-up was 67.4 months (range, 60.0‒77.9). HR (95% CI) for OS was 0.55 (0.44‒0.69) for patients with PD-L1 TPS≥50% and 0.70 (0.61‒0.80) with PD-L1 TPS≥1%. Five-year OS rates for pembrolizumab versus docetaxel were 25.0% versus 8.2% in patients with PD-L1 TPS≥50% and 15.6% versus 6.5% with PD-L1 TPS≥1%.

Bispective, national and multicentric study including consecutively aNSCLC patients who initiated first-line pembrolizumab monotherapy...KRAS mutated: 27.7%, PDL1 TPS > 75%: 53.7%...With a median follow up of 25,8 [95%CI: 24,8-26,7] months, median rwPFS and median OS were 8,2 [95%CI: 6,9-9,5] and 22,6 [95%CI: 18,5-27,4] months, respectively; 6, 12, 18-months survival rates were 76,8%, 64,8% and 54,3%....

Subgroup analysis by PD-L1 suggested that nivolumab plus ipilimumab plus chemotherapy was associated with the best OS in patients with PD-L1 <1%...pem-chemo and nivo-ipi-chemo appear to be superior first-line immunotherapy combinations for advanced NSCLC patients with positive and negative PD-L1 expression, respectively.

...we identified adult patients with histologically confirmed, PD-L1 TPS ≥1%, advanced (stage IIIB or IV) NSCLC treated with at least one prior chemotherapy regimen and who initiated pembrolizumab monotherapy…Clinical outcomes among previously treated advanced, PD-L1 expressing NSCLC patients were consistent with clinical trial results thus supporting the effectiveness of pembrolizumab...

...phase II trial, 62 patients with advanced NSCLC and a rigorously ascribed ECOG performance status of 2 received pembrolizumab (200 mg every 3 weeks) monotherapy in the first- or subsequent-line treatment setting...Among all patients irrespective of tumor PD-L1 expression, 38% achieved durable clinical benefit (co-primary endpoint defined as complete response, partial response, or stable disease.

Pembro improved OS vs chemo in all populations (Table); in pts with PD-L1 TPS ≥1%, the 24-mo rate for OS was 43.8% vs 28.2%, PFS was 15.6% vs 10.6%, and PFS2 was 26.4% vs 8.6%. In 22 pts who completed 35 cycles of pembro, ORR was 77.3% and median DOR was 27.6 mo. In this longer-term follow-up (∼3 y), 1L pembro monotherapy continued to improve OS with a manageable safety profile vs platinum-based chemo in Chinese pts with locally advanced/metastatic NSCLC without sensitizing EGFR/ALK aberrations and PD-L1 TPS ≥1%. Most pts who completed 2 y of pembro had durable responses. These findings support 1L use of pembro for PD-L1–positive advanced/metastatic NSCLC in China.

This was a non-randomized, open label phase II trial...outcomes of elderly patients (pt) with advanced non-small cell lung cancer (NSCLC), treated with pembrolizumab (P) in the first-line setting. ORR was Partial Response, Stable Disease and Progression Disease in 18 (29%), 30 (48.3%), and 14 (22.5%) pt. Single P seems safe and effective in EP with untreated, PD-L1 positive, advanced NSCLC.

The median PFS was significantly higher in RAD51Bme+ patients (p = 0.0216; Figure 3A). Furthermore, patients with RAD51Bme+ disclosed a lower risk of disease progression (HR 0.37; 95% CI: 0.15–0.88; p = 0.025) compared with RAD51Bme-….PD-L1+ and RAD51Bme+ are promising biomarkers to predict response to PD-1 blockade rather than overall prognostic factors in NSCLC’s patients.

Patients with tumors showing PD-L1 expression ≥ 1% in stromal/immune cells had a longer OS than those with PD-L1 <1% (median OS 11·0 months [95% CI 8·73-NR] versus 2·73 months [95% CI 1-NR], p=0·031;...

Pts received by nivolumab (87.2%), pembrolizumab (7.7%) or atezolizumab (5.1%)….PD-L1 status was assessed in 18 tumours (46.1%). In PDL1+ pts, ORR was 53.3% (8/15) and DCR was 66.7% (10/15).

Overall, the three antibodies provide a significant differential effect in terms of activity according to PD-L1 expression on tumor cells. The predictive value of PD-L1 on tumor cells seems to be more robust for anti-PD-1 antibody (nivolumab and pembrolizumab), and in the context of advanced melanoma and NSCLC.

A 59-year-old male was diagnosed with advanced NSCLC with a PD-L1 expression of 35% (Stage IIIB, Grade III)...The patient has been receiving a systemic therapy consisting of platinum-based doubled chemotherapy and pembrolizumab since November 2019 with maintaining immunotherapy until the present...By December 2020, the patient achieved a complete metabolic response as evidenced by most recent PET-CT reports.

With PD-L1 expression of TPS 30 %, nab-paclitaxel plus pembrolizumab was administered as fifth-line treatment and achieved partial response, with sustained response ongoing for 7 months as of January 31, 2020.

The findings from the present study revealed that PD1L1 could be used as a predictive biomarker, and the application of combination treatment of pembrolizumab and 125I showed promising effects on NSCLC….the combination of Pem and 125I could induce tumor cell apoptosis up to ~65%, whereas the single Pem or 125I radiation treatment groups only induced apoptosis to <40%.