Table 1.
FDA-approved chemotherapy and immunotherapy combinations.
| Cancer | Line of Therapy | PD-L1 Positivity Criteria | Chemotherapy | ICI | Clinical Benefit | Trial Name |
|---|---|---|---|---|---|---|
| NSCLC-non-squamous | Metastatic, first-line | Regardless of PD-L1 tumor expression | Pemetrexed + carboplatin | Pembrolizumab | OS at 12 m: 69.2% vs. 49.4%. HR 0.49; [95% CI 0.38–0.64]; p < 0.00001 | Keynote-189 [4] |
| NSCLC-squamous | Metastatic, first-line | Regardless of PD-L1 tumor expression | Carboplatin + paclitaxel/ nab paclitaxel | Pembrolizumab | OS: 15.9 vs. 11.3 m. HR 0.64; [95% CI 0.49–0.85]; p = 0.001 | Keynote-407 [68] |
| NSCLC-non-squamous | Metastatic, first-line | Regardless of PD-L1 tumor expression | Carboplatin + paclitaxel + bevacizumab | Atezolizumab | OS: 19.2 vs. 14.7 m. HR 0.78; [95% CI 0.64–0.96]; p = 0.01 | IMpower 150 [69] |
| NSCLC-non-squamous | Metastatic, first-line | Regardless of PD-L1 tumor expression | Carboplatin + nab paclitaxel |
Atezolizumab | OS: 18.6 vs. 13.9 m. HR 0.8; [95% CI 0.64–0.99]; p = 0.03 | IMpower 130 [5] |
| NSCLC | Metastatic, first-line | Regardless of PD-L1 tumor expression | Platinum doublet | Nivolumab + ipilimumab | OS 15.6 vs. 10.9 m; HR 0.69; [95% CI 0.55–0.80]; p = 0.00065 | CheckMate-9LA [70] |
| NSCLC | Neoadjuvant | Regardless of PD-L1 tumor expression | Platinum-based chemotherapy | Nivolumab | EFS 31.6 vs. 20.8 m. HR 0.63; [97.3% CI, 0.43–0.91]; p = 0.005. pCR 24.0% vs. 2.2%. OR: 13.9; [99% CI, 3.4–55.7]; p < 0.001 | Checkmate-816 [71] |
| NSCLC | Metastatic | PD-L1 expression on ≥1% of tumor cells | Platinum-based chemotherapy + tremelimumab | Durvalumab | Reduced the risk of death by 23% HR 0.77; [95% CI 0.65 to 0.92]; p = 0.00304 |
POSEIDON Phase III trial [83] |
| NSCLC | Metastatic, first-line | Regardless of PD-L1 tumor expression | Adjuvant treatment following surgical resection and platinum-based chemotherapy | Pembrolizumab | Reduced the risk of disease recurrence or death by 27%; HR 0.73; [95% CI, 0.60 to 0.89] | KEYNOTE-091 [84] |
| SCLC | Extensive stage, first-line |
Regardless of PD-L1 tumor expression | Carboplatin + etoposide | Atezolizumab concurrent and maintenance | OS: 12.3 vs. 10.3 m. HR 0.70; [95% CI 0.54–0.91]; p = 0.006 | IMpower 133 [73] |
| SCLC | Extensive stage, first-line |
Regardless of PD-L1 tumor expression | Carboplatin + etoposide | Durvalumab | OS: 13 vs. 10.3 m. HR 0.73; [95% CI 0.59–0.91]; p = 0.0047 | CASPIAN [62] |
| HNSCC | Metastatic first-line | Regardless of PD-L1 tumor expression | Platinum + 5-FU or platinum + 5-FU + cetuximab |
Pembrolizumab | OS: 13.6 vs. 10.4 m. (CPS ≥ 1) HR 0.65; [95% CI 0.53–0.80]; p < 0.03 | Keynote-048 [77] |
| Esophagus cancer | Metastatic, first-line | Regardless of PD-L1 tumor expression | 5-fluorouracil + cisplatin | Pembrolizumab | OS: 12.4 vs. 9.8 m. HR 0.73; [CI 0.62–0.86]; p < 0.0001 | Keynote-590 [78] |
| Esophagus cancer | Metastatic, first-line | Regardless of PD-L1 tumor expression | Fluropyrimidine + platinum-based | Nivolumab | OS: 13.2 vs. 10.7 m. HR 0.74; [99.1% CI, 0.58–0.96]; p = 0.002 | Checkmate 648 [79] |
| Gastric/ esophagus cancer | Metastatic, first-line | Regardless of PD-L1 tumor expression | Capecitabine + oxaliplatin or leucovorin + fluorouracil + oxaliplatin |
Nivolumab | OS: 13.1 vs. 11.1 m. HR 0.71; [98.4% CI 0.59–0.86]; p < 0.0001 |
Check-Mate-649 [16] |
| Gastric cancer | Metastatic, first-line | Regardless of PD-L1 tumor expression | Trastuzumab + 5-fluorouracil + cisplatin or capecitabine + oxaliplatin |
Pembrolizumab | 22.7% improvement in OR [95% CI 11.2–33.7]; p = 0.00006. CR 11.3% vs. 3.1% | Keynote-811 [17] |
| TNBC | Metastatic, first-line | PD-L1 + tumor cells (CPS ≥ 10) | Nab paclitaxel or paclitaxel or carboplatin + Gemcitabine | Pembrolizumab | PFS (CPS > 10): 9.7 vs. 5.6 m. HR 0.65; [95% CI 0.49–0.86]; p = 0.0012 | Keynote 355 [74] |
| TNBC | Neoadjuvant | Regardless of PD-L1 tumor expression | Carboplatin + paclitaxel, followed by doxorubicin or epirubicin + cyclophosphamide | Pembrolizumab | 37% reduction in the risk of disease progression. HR = 0.63; [95% CI, 0.48–0.82]; p = 0.0003 | Keynote-522 [75] |
| TNBC | Metastatic, first-line | PD-L1 + tumor cells (≥1%). | Nab paclitaxel | Atezolizumab | OS: 25.0 vs. 15.5 m. PD-L1(+) HR 0.62; [95% CI 0.45–0.86] | IMpassion 130 [76] |
| Cervical cancer | Metastatic, first-line | Regardless of PD-L1 tumor expression | Paclitaxel + cisplatin or paclitaxel + carboplatin +/− bevacizumab |
Pembrolizumab | ORR 68% vs. 50%. Median of duration response 18.0 vs. 10.4 m | Keynote-826 [82] |
| Biliary tract cancer | Metastatic, first-line | Regardless of PD-L1 tumor expression | Gemcitabine + cisplatin | Durvalumab | Reduced the risk of death by 20% HR 0.80; [95% CI 0.66–0.97]; p = 0.021 | TOPAZ-1 [81] |
| Bladder cancer | Metastatic, first-line maintenance | Regardless of PD-L1 tumor expression | Gemcitabine + cisplatin/carboplatin | Avelumab | OS 21.4 vs. 14.3 m; HR 0.69; [95% CI 0.56 to 0.86]; p = 0.001 | JAVELIN Bladder 100 [80] |
NSCLC: Non-Small Cell Lung Cancer; SCLC: Small Cell Lung Cancer; HNSCC: Head and Neck Squamous Cell Carcinoma; TNBC: Triple Negative Breast Cancer; ICI: Immune Checkpoint Inhibitor; OS: Overall Survival; m: month; HR: Hazard Ratio; CI: Confidence Interval; CPS: Combined Positive Score; EFS Event Free survival; pCR: pathological Complete Response.