| pathology | Benefit (demonstrated or suggested) and harm | | | |
|---|
| gastric or gastro-oesophageal junction cancer (advanced) | All results are NS for efficacy inferior to paclitaxel in terms of PFS in Keynote 061, 2018 (2L patients) | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| KEYNOTE-059 | vs paclitaxel | | | | | Keynote 061, 2018 | vs paclitaxel | | PFS 1.27 [1.03; 1.57] median 1.5 mo vs. 4.1 mo | OS 0.82 [0.66; 1.02] median 9.1 mo vs. 8.3 mo |
| Trial | Treatments | Patients | Method |
|---|
| KEYNOTE-059 | (n=-9) vs. (n=-9) | | Single-arm study Sample size: -9/-9 Primary endpoint: FU duration: | | Keynote 061, 2018 | pembrolizumab (n=-9) vs. paclitaxel (n=-9) | patients with advanced gastric or gastro-oesophageal junction cancer that progressed on first-line chemotherapy with a platinum and fluoropyrimidine and who had a PD-L1 CPS of 1 or higher | open label Sample size: -9/-9 Primary endpoint: FU duration: |
|
| Head and neck cancer | All results are NS for efficacy | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| KEYNOTE-040 | vs standard treatment | OS 0.81 [0.66; 0.99] | | |
| Trial | Treatments | Patients | Method |
|---|
| KEYNOTE-040 | pembrolizumab 200 mg intravenous (IV) on Day 1 of each 3-week cycle (n=-9) vs. standard treatment (methotrexate, docetaxel or cetuximab) (n=-9) | patients with recurrent or metastatic head and neck squamous cell cancer | open-design Sample size: -9/-9 Primary endpoint: OS FU duration: |
|
| lung cancer (metastatic) | superior to platinum-based CT in terms of overall survival in Keynote 189, 2018 (1L PD-L1 positive nonsquamous patients) superior to platinum-based CT in terms of PFS in Keynote 189, 2018 (1L PD-L1 positive nonsquamous patients) | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| Keynote 042 (>=1%), 2018 | vs platinum-based CT | overall survival 0.81 [0.71; 0.93] median 16.7 mo vs. 12.1 mo | | | | Keynote 024, 2015 | vs platinum-based CT | overall survival 0.60 [0.41; 0.88] median not reached vs. not reached PFS 0.50 [0.37; 0.68] median 10.3 mo vs. 6.0 mo | | | | Keynote 010 2mg, 2015 | vs platinum-based CT | overall survival 0.71 [0.58; 0.87] median 10.4 mo vs. 8.5 mo | | PFS 0.88 [0.74; 1.05] median 3.9 mo vs. 4.0 mo | | Keynote 010 10mg, 2015 | vs platinum-based CT | overall survival 0.61 [0.49; 0.75] median 12.7 mo vs. 8.5 mo PFS 0.79 [0.66; 0.94] median 4.0 mo vs. 4.0 mo | | | | KEYNOTE-021 phase 2, 2016 | vs platinum-based CT | overall survival 0.54 [0.33; 0.88] median 19 mo vs. 8.9 mo PFS 0.53 [0.31; 0.91] median 13.0 mo vs. 8.9 mo | | | | Keynote 189, 2018 | vs platinum-based CT | overall survival 0.49 [0.38; 0.64] median 11.3 mo vs. not reached Demonstrated PFS 0.52 [0.43; 0.63] median 8.8 mo vs. 4.9 mo Demonstrated | | | | Keynote 407, 2018 | vs platinum-based CT | overall survival 0.64 [0.49; 0.84] median 15.9 mo vs. 11.2 mo | | | | Keynote 042 (>=50%), 2018 | vs platinum-based CT | overall survival 0.69 [0.56; 0.85] median 20.0 mo vs. 12.2 mo | | | | Keynote 042 (>=20%), 2018 | vs platinum-based CT | overall survival 0.77 [0.64; 0.92] median 17.7 mo vs. 13.0 mo | | |
| Trial | Treatments | Patients | Method |
|---|
| Keynote 042 (>=1%), 2018 | pembrolizumab 200 mg every 3 wk for 35 cycles or until disease progression, intolerable toxicity (n=637) vs. investigator's choice of carboplatin plus paclitaxel or carboplatin plus pemetrexed for a maximum of 6 cycles (n=637) | Treatment Naïve Subjects With PD-L1 Positive Advanced or Metastatic Non-Small Cell Lung Cancer | open label Parallel groups Sample size: 637/637 Primary endpoint: Overall survival FU duration: 12.8-mo median | | Keynote 024, 2015 | Pembrolizumab (200 mg, administered as intravenous (IV) infusion on Day 1 of each 21-day cycle for up to 35 cycles or until documented PD
(n=154) vs. standard of care (SOC) platinum-based chemotherapies
(n=151) crossover from the chemotherapy group to the pembrolizumab group was permitted in
the event of disease progression
| previously
untreated advanced NSCLC with PD-L1 expression on at least 50% of tumor cells
and no sensitizing mutation of the epidermal growth factor receptor gene or translocation
of the anaplastic lymphoma kinase gene | open label Parallel groups Sample size: 154/151 Primary endpoint: PFS, OS FU duration: 11.2 months (median) in the chemotherapy group,
66 patients (43.7%) crossed over to receive pembrolizumab
after disease progression
| | Keynote 010 2mg, 2015 | pembrolizumab
2 mg/kg (n=345) vs. docetaxel 75 mg/m² every 3 weeks (n=343) | patients
with previously treated non-small-cell lung cancer with PD-L1 expression on at least 1% of tumour cells | open-label Parallel groups Sample size: 345/343 Primary endpoint: OS FU duration: | | Keynote 010 10mg, 2015 | pembrolizumab
10 mg/kg
(n=346) vs. docetaxel 75 mg/m² every 3 weeks
(n=343)
| patients
with previously treated non-small-cell lung cancer with PD-L1 expression on at least 1% of tumour cells
| open-label Sample size: 346/343 Primary endpoint: OS FU duration:
| | KEYNOTE-021 phase 2, 2016 | 24 months treatment with pembrolizumab (200mg every three weeks)+ CT (n=60) vs. four cycles of carboplatin and pemetrexed (500 mg/m2 every three weeks) (n=63) | patients with stage IIIB/IV, chemotherapy-naive, nonsquamous non-small-cell lung cancer | open design Parallel groups Sample size: 60/63 Primary endpoint: ORR FU duration: phase 1/2 | | Keynote 189, 2018 | pemetrexed
and a platinum-based drug plus 200 mg of pembrolizumab, followed by pembrolizumab for up to a total of
35 cycles plus pemetrexed maintenance therapy (n=410) vs. pemetrexed
and a platinum-based drug plus placebo every
3 weeks for 4 cycles, followed by placebo (n=206) | participants with advanced or metastatic nonsquamous non-small cell lung cancer (NSCLC) who have not previously received systemic therapy for advanced disease and without sensitizing EGFR or ALK mutations | double-blind Parallel groups Sample size: 410/206 Primary endpoint: PFS, OS FU duration: 10.5 mo median crossover permited | | Keynote 407, 2018 | pembrolizumab + carboplatin and paclitaxel or nano particle albumin-bound paclitaxel (nab-paclitaxel) (n=278) vs. carboplatin and paclitaxel or nano particle albumin-bound paclitaxel (nab-paclitaxel) (n=281) | adults with first line metastatic squamous non-small cell lung cancer | open-label Parallel groups Sample size: 278/281 Primary endpoint: OS, PFS FU duration: 7?7 mo (median) | | Keynote 042 (>=50%), 2018 | pembrolizumab
(n=299) vs. SOC Treatment (Platinum-based Chemotherapy)
(n=300)
| Treatment Naïve Subjects With PD-L1 Positive Advanced or Metastatic Non-Small Cell Lung Cancer
| open label Sample size: 299/300 Primary endpoint: Overall survival FU duration: 12.8-mo median
| | Keynote 042 (>=20%), 2018 | pembrolizumab
(n=413) vs. SOC Treatment (Platinum-based Chemotherapy)
(n=405)
| Treatment Naïve Subjects With PD-L1 Positive Advanced or Metastatic Non-Small Cell Lung Cancer
| open label Parallel groups Sample size: 413/405 Primary endpoint: Overall survival FU duration: 12.8-mo median
|
|
| melanoma | superior to pembrolizumab 10mg/kg in terms of recurrence free survival in KEYNOTE-054, 2018 (adjuvant patients) inferior to pembrolizumab 10mg/kg in terms of Vitiligo any grade in KEYNOTE-006 (every 2W), 2015 (1L patients) inferior to pembrolizumab 10mg/kg in terms of Grade 3 or 4 drug-related adverse events in KEYNOTE-054, 2018 (adjuvant patients) inferior to pembrolizumab 10mg/kg in terms of Vitiligo any grade in KEYNOTE-054, 2018 (adjuvant patients) inferior to pembrolizumab 10mg/kg in terms of Vitiligo any grade in KEYNOTE 002 (2mg/kg Q3W), 2015 (2L patients) inferior to pembrolizumab 10mg/kg in terms of Vitiligo any grade in KEYNOTE-006 (every 3W), 2015 (1L patients) | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| KEYNOTE-001, 2014 | vs pembrolizumab 10mg/kg | | | OS 1.09 [0.68; 1.75] PFS 0.84 [0.57; 1.23] Adverse events leading to discontinuation of drug 0.63 [0.23; 1.69] overall response rate 0.99 [0.58; 1.67] Grade 3 or 4 drug-related adverse events 1.75 [0.73; 4.18] serious drug-related adverse events 6.61 [0.83; 52.57] | | KEYNOTE-006 (every 2W), 2015 | vs pembrolizumab 10mg/kg | OS 0.68 [0.53; 0.87] median NA vs. 16 months PFS 0.58 [0.46; 0.73] Grade 3 or 4 drug-related adverse events 0.67 [0.45; 0.98] | Vitiligo any grade 5.76 [2.03; 16.31] | Vitiligo grade 3-4 NaN [NaN; NaN] | | KEYNOTE-054, 2018 | vs pembrolizumab 10mg/kg | recurrence free survival 0.57 [0.43; 0.75] Demonstrated PFS LP-D1 positif 0.54 [0.42; 0.69] PFS PD-L1 negatif 0.47 [0.26; 0.85] PFS 0.57 [0.43; 0.75] | Grade 3 or 4 drug-related adverse events 4.35 [2.61; 7.26] Vitiligo any grade 2.96 [1.34; 6.52] | Vitiligo grade 3-4 NaN [NaN; NaN] | | KEYNOTE 002 (2mg/kg Q3W), 2015 | vs pembrolizumab 10mg/kg | PFS 0.57 [0.45; 0.73] median 2.9 mo vs. 2.7 mo | Vitiligo any grade 4.80 [1.07; 21.61] | Vitiligo grade 3-4 NaN [NaN; NaN] | | KEYNOTE-006 (every 3W), 2015 | vs pembrolizumab 10mg/kg | OS 0.68 [0.53; 0.87] median NA vs. 16 months PFS 0.58 [0.47; 0.72] Grade 3 or 4 drug-related adverse events 0.51 [0.33; 0.78] | Vitiligo any grade 7.16 [2.56; 20.01] | Vitiligo grade 3-4 NaN [NaN; NaN] | | KEYNOTE 002 (10mg/kg Q3W), 2015 | vs pembrolizumab 10mg/kg | PFS 0.50 [0.39; 0.64] median 2.9 mo vs. 2.7 mo | | Vitiligo any grade 4.30 [0.94; 19.61] Vitiligo grade 3-4 NaN [NaN; NaN] |
| Trial | Treatments | Patients | Method |
|---|
| KEYNOTE-001, 2014 | intravenous pembrolizumab at 2 mg/kg every 3 weeks (n=89) vs. intravenous pembrolizumab at 10 mg/kg every 3 weeks (n=84) | patients (aged ¡Ý18 years) with advanced melanoma whose disease had progressed after at least two ipilimumab doses | open-label Parallel groups Sample size: 89/84 Primary endpoint: ORR FU duration: | | KEYNOTE-006 (every 2W), 2015 | pembrolizumab (at a dose of 10 mg per kilogram of body weight) every 2 weeks or every 3 weeks (n=-9) vs. four doses of ipilimumab (at 3 mg per kilogram) every 3 weeks (n=-9) 3 arms: pembrolizumab (at a dose of 10 mg per kilogram of body weight) every 2 weeks or every 3 weeks or four doses of ipilimumab (at 3 mg per kilogram) every 3 weeks | patients with advanced melanoma who had received no more than one previous systemic therapy for advanced disease 12% of second line patients was included | open-label Parallel groups Sample size: -9/-9 Primary endpoint: PFS, OS FU duration: | | KEYNOTE-054, 2018 | Pembrolizumab (Participants receive pembrolizumab 200 mg intravenously (IV) on Day 1 of each 21-day cycle for up to 1 year)
(n=514) vs. placebo (n=505) | patients with complete Resection of High-Risk Stage III Melanoma | double-blind Parallel groups Sample size: 514/505 Primary endpoint: Recurrence-free survival , FU duration: 15 months (median) | | KEYNOTE 002 (2mg/kg Q3W), 2015 | Pembrolizumab 2 mg/kg IV Q3W (n=180) vs. investigator-choice
chemotherapy (paclitaxel plus carboplatin, paclitaxel, carboplatin, dacarbazine, or oral temozolomide) (n=179) 3 arms ntravenous pembrolizumab 2 mg/kg or 10 mg/kg every 3 weeks or investigator-choice
chemotherapy | patients with unresectable or metastatic melanoma and disease progression following ipilimumab and, if BRAFV600 mutation positive, a BRAF inhibitor | open design Parallel groups Sample size: 180/179 Primary endpoint: PFS FU duration: phase 2 | | KEYNOTE-006 (every 3W), 2015 | Pembrolizumab Every 3 Weeks
(n=277) vs. Ipilimumab (Participants receive ipilimumab, 3 mg/kg IV, once every 3 weeks for a total oPembrolizumab Every 2 Weeks (Participants receive pembrolizumab, 10 mg intravenously (IV), once every 2 weeks for up to 2 years)
2/ Pembrolizumab Every 3 Weeks (P (n=278) 3 arms: pembrolizumab (at a dose of 10 mg per
kilogram of body weight) every 2 weeks or every 3 weeks or four doses of ipilimumab
(at 3 mg per kilogram) every 3 weeks.
| patients with unresectable stage III or IV advanced melanoma and who had received no more than one previous
systemic therapy for advanced disease
12% of second line patients was included | open label Parallel groups Sample size: 277/278 Primary endpoint: PFS, OS FU duration: | | KEYNOTE 002 (10mg/kg Q3W), 2015 | intravenous pembrolizumab 10 mg/kg every 3 weeks (n=181) vs. investigator-choice
chemotherapy (paclitaxel plus carboplatin, paclitaxel, carboplatin, dacarbazine, or oral temozolomide)
(n=179) 3 arms ntravenous pembrolizumab 2 mg/kg or 10 mg/kg every 3 weeks or investigator-choice
chemotherapy
| patients with unresectable or metastatic melanoma and disease progression following ipilimumab and, if BRAFV600 mutation positive, a BRAF inhibitor
| open design Parallel groups Sample size: 181/179 Primary endpoint: PFS FU duration: phase 2
|
|
| multiple myeloma | All results are NS for efficacy inferior to lenalidomide, dexamethasone in terms of PFS in KEYNOTE-183, 2018 (rrMM patients) | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| KEYNOTE-183, 2018 | vs lenalidomide, dexamethasone | | PFS 1.53 [1.05; 2.22] median 7.8 mo vs. 8.6 mo | OS 1.61 [0.91; 2.85] median NR vs. 15.2 mo | | KEYNOTE-185, 2018 | vs lenalidomide, dexamethasone | | | |
| Trial | Treatments | Patients | Method |
|---|
| KEYNOTE-183, 2018 | pembrolizumab, Pomalidomide and low-dose Dexamethasone (n=125) vs. Pomalidomide and low-dose Dexamethasone (n=124) | refractory or relapsed and refractory Multiple Myeloma (rrMM) | open-design Parallel groups Sample size: 125/124 Primary endpoint: FU duration: 7.8 mo / 8.6 mo (median) | | KEYNOTE-185, 2018 | (n=151) vs. lenalidomide and low-dose dexamethasone (n=150) | newly diagnosed and treatment naïve Multiple Myeloma who are ineligible for autologous stem cell transplant Only 301 of the 640 planned had been enrolled when the trial was halted | open-design Parallel groups Sample size: 151/150 Primary endpoint: FU duration: |
|
| urothelial carcinoma (advanced) | All results are NS for efficacy | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| KEYNOTE-045, 2017 | vs chemotherapy | OS 0.73 [0.59; 0.91] median 10.3 months vs. 7.4 months | | PFS 0.98 [0.81; 1.19] | | Keynote 361 monotherapy | vs chemotherapy | | | | | KEYNOTE-052, 2017 | vs chemotherapy | | | |
| Trial | Treatments | Patients | Method |
|---|
| KEYNOTE-045, 2017 | pembrolizumab (n=270) vs. investigator's choice of chemotherapy with paclitaxel, docetaxel, or vinflunine (n=272) | patients with advanced urothelial cancer that recurred or progressed after platinum-based chemotherapy | open-label Parallel groups Sample size: 270/272 Primary endpoint: OS FU duration: | | Keynote 361 monotherapy | pembrolizumab 200 mg every 3 weeks (Q3W) (n=990) vs. chemotherapy alone (n=0) 3 arms: pembrolizumab ± chemotherapy versus chemotherapy | patients with histologically or cytologically confirmed unresectable/metastatic urothelial carcinoma | Sample size: 990/0 Primary endpoint: FU duration: | | KEYNOTE-052, 2017 | intravenous pembrolizumab 200 mg every 3 weeks (n=374) vs. (n=-9) | cisplatin-ineligible patients with advanced urothelial cancer who had not been previously treated with systemic chemotherapy | open-design Single-arm study Sample size: 374/-9 Primary endpoint: ORR FU duration: 5 months (median) phase 2, single arm |
|
