Table 1.
Approved indications and diagnostic devices for PD‐[L]1 inhibitors
| Indications | PD‐1/PD‐L1 drugs approved (p denotes pediatric indication as well) | Companion diagnostics | Complementary diagnostics | Approved combinations |
|---|---|---|---|---|
| Dermatologic | ||||
| Advanced/metastatic melanoma | Atezolizumab (1st L‐C), nivolumab (1st L‐M; 1st L‐C), pembrolizumab (1st L‐M) | Nonea | None | Atezolizumab + vemurafenib + cobimetinib, 1st L if positive for BRAF V600E/K mutation; nivolumab + ipilimumab, 1st L |
| Adjuvant melanoma | Nivolumab (M), pembrolizumab (M) | None | None | None |
| Merkel cell, metastatic | Avelumab (1st L)p; pembrolizumab (1st L)p | None | None | None |
| Cutaneous SCC | Cemiplimab‐rwlc (M), pembrolizumab (M) | None | None | None |
| Thoracic | ||||
| Advanced/metastatic NSCLC | Atezolizumab (1st L‐M; 1st L‐C, 2nd L‐M)*, nivolumab (1st L‐C; 2nd L‐M)*, pembrolizumab (1st L‐M; 1st L‐C; 2nd L‐M)*, *2nd L: after platinum | Atezolizumab: 1st L‐M for patients with no EGFR or ALK aberrations AND either TC ≥50% or IC ≥10% (Ventana SP142); nivolumab: 1st L‐C for patients with no EGFR or ALK aberrations AND TC ≥1% (Dako 28–8); pembrolizumab: 1st L‐M for with no EGFR or ALK aberrations AND TPS ≥1% (Dako 22C3), 2nd L‐M for TPS ≥1% (Dako 22C3) | Nivolumab: TC ≥1%, 5%, 10% (Dako 28–8); atezolizumab: TC ≥1% or IC ≥1% (Ventana SP142) | Atezolizumab + bevacizumab + carboplatin + paclitaxel for nonsquamous, 1st L; nivolumab, 1st L: with ipilimumab (for patients with PD‐L1 TC ≥1%), with ipilimumab and 2 cycles platinum doublet (regardless of PD‐L1 expression); pembrolizumab, 1st L: with carboplatin and either paclitaxel or nab‐paclitaxel, for squamous, with pemetrexed and platinum, for nonsquamous, non‐EGFR/‐ALK mutated |
| Post‐chemoradiation NSCLC | Durvalumab (for stage III following platinum‐based chemoRT without progression, for ≤12 months) (M) | None | None | None |
| Small cell lung cancer | Atezolizumab (1st L‐C); durvalumab (1st L‐C); nivolumab (3rd L)*b; pembrolizumab (3rd L)*b; *3rd L: after platinum and at least 1 other line of therapy | None | None | Atezolizumab + carboplatin + etoposide, 1st L; durvalumab + [carbo/cis]platin + etoposide, 1st L |
| Head and neck squamous cell carcinoma | Nivolumab (2nd L‐M after platinum); pembrolizumab (1st L‐C; 1st L‐M; 2nd L‐M) | Pembrolizumab 1st L‐M for CPS ≥1 (Dako 22C3) | Nivolumab: TC ≥1%, 5%, 10% (Dako 28–8) | Pembrolizumab + platinum +5FU, 1st L |
| Genitourinary | ||||
|
Advanced urothelial |
Atezolizumab (1st L‐M, 2nd L‐M): 1st L platinum‐ineligible, 1st L cisplatin‐ineligible if PD‐L1+ IC ≥5%, 2nd L after platinumc; avelumab (maintenance, 2nd L‐M) maintenance following 1st L platinum, 2nd L after platinum; durvalumab (2nd L‐M)c; nivolumab (2nd L‐M); pembrolizumab (1st L‐M, 2nd L‐M) 1st L platinum‐ineligible; 1st L cisplatin‐ineligible PD‐L1 CPS ≥10% 2nd L (progressed ≤1 year after platinum) | Atezolizumab, cisplatin‐ineligible IC ≥5% (Ventana SP142); pembrolizumab, cisplatin‐ineligible CPS ≥10 (Dako 22C3) | Durvalumab: TC ≥25%; or ICP >1% with PD‐L1+ IC ≥25%; or ICP 1% with PD‐L1+ IC = 100% (Ventana SP 263); nivolumab: TC ≥1% (Dako 28–8) | None |
| Nonmuscle invasive bladder cancer | Pembrolizumab (BCG‐unresponsive carcinoma in situ with or without papillary tumors, cystectomy‐ineligible) (M) | None | None | None |
| RCC | Nivolumab intermediate‐/poor‐risk: 1st L‐C with ipi, 2nd L‐M after antiangiogenic therapy; pembrolizumab (1st L‐C); avelumab (1st L‐C) | None | None |
Nivolumab + ipilimumab, 1st L pembrolizumab + axitinib, 1st L avelumab + axitinib, 1st L |
| Gastrointestinal | ||||
| HCC | Atezolizumab (1st L‐C); nivolumab (2nd L‐C, 2nd L‐M after sorafenib); pembrolizumab (2nd L‐M after sorafenib) | None | None | Atezolizumab + bevacizumab, 1st L; nivolumab + ipilimumab, 2nd L |
| MSI‐H CRC | Nivolumab (3rd L‐M after 5FU, oxaliplatin, and irinotecan; or 3rd L‐C w/ ipilimumab)p; pembrolizumab (1st L‐M) | None | None | None |
| Gastric/GE junction | Pembrolizumab (after at least 5FU and platinum) (2nd L‐M) | Pembrolizumab CPS ≥1 (Dako 22C3) | None | None |
| Esophageal SCC | Nivolumab (2nd L‐M); pembrolizumab (2nd L‐M) | Pembrolizumab CPS ≥10 (Dako 22C3) | ||
| Gynecologic/breast | ||||
| Cervical SCC | Pembrolizumab (2nd L‐M) | Pembrolizumab CPS ≥1 (Dako 22C3) | ||
| Endometrial | Pembrolizumab (2nd L‐C) | None | None | Pembrolizumab + lenvatinib, 2nd L |
| TNBC | Atezolizumab (1st L‐C) | Atezolizumab IC ≥1 (Ventana SP142) | Atezolizumab + nab‐paclitaxel | |
| Hematologic | ||||
| Classic Hodgkin lymphoma | Nivolumab (relapsed/refractory to autoSCT and brentuximab, or 4th L‐M after autoSCT); pembrolizumab (4th L‐M)p | None | None | None |
| PMBCL | Pembrolizumab (3rd L‐M)p | None | None | None |
| MSI‐H tissue‐agnostic | Pembrolizumab (progressed following prior treatment and no satisfactory alternatives)p (M) | None; PMCs pending for MSI and MMR | None | None |
| TMB‐high tissue‐agnostic | Pembrolizumab (≥10 mutations/megabase, progressed following prior treatment and no satisfactory alternatives)p (M) | FoundationOneCDx assay | None | None |
Note: all indications are in advanced (unresectable or metastatic) disease unless otherwise noted.
BRAF kit (THxID) is used to select BRAF+ patients for the combination of atezolizumab with vemurafenib plus cobimetinib.
Nivolumab indication was withdrawn by the sponsor on December 29, 2020. Pembrolizumab indication was withdrawn by the sponsor on March 1, 2021.
Durvalumab indication was withdrawn by the sponsor on February 22, 2021. Atezolizumab indication was drawn by the sponsor on March 7, 2021.
Abbreviations: 5FU, fluoropyrimidine; autoSCT, autologous stem cell transplant; C, combination; chemoRT, concurrent chemotherapy and radiation therapy; CPS, combined proportion/positive score; IC, immune cell; ipi, ipilimumab; L, line (e.g., 2nd L, 2nd line); M, monotherapy (e.g., 3rd L‐M, 3rd‐line monotherapy); p, pediatric; PMC, postmarketing commitment; PMLBCL, primary mediastinal large B‐cell lymphoma; RFS, recurrence‐free survival; TMB, tumor mutation burden; TC, tumor cell; TPS, tumor proportion score; TNBC, triple‐negative breast cancer.