Table 1.
Characteristics of the studies and participants.
| Source | Trial name | NCT # | Phase | Total pt # | Cancer type | Line of therapy | Treatment arms | Pt # | OS HR (95% CI) | Sex | Pt # | OS HR (95% CI) | Age | Pt # | OS HR (95% CI) | ECO G PS | Pt # | OS HR (95% CI) | Smoking status | Pt # | OS HR (95% CI) |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 2015-Brahmer-N Engl J Med | CheckMate 017 | NCT01642004 | 3 | 272 | Squamous | >1 | Nivolumab vs. docetaxel | 272 | 0.59 (0.44-0.78) | Male | 208 | 0.57 (0.41-0.78) | <65 | 152 | 0.52 (0.35-0.75) | 0 | 64 | 0.48 (0.24-0.99) | Current/former smoker | 250 | 0.59 (0.44-0.80) |
| Female | 64 | 0.67 (0.36-1.25) | ≥65 to <75 | 91 | 0.56 (0.34-0.91) | 1 | 206 | 0.54 (0.39-0.74) | |||||||||||||
| 2015-Borghaei-N Engl J Med | CheckMate 057 | NCT01673867 | 3 | 582 | Nonsquamous | >1 | Nivolumab vs. docetaxel | 582 | 0.75 (0.62-0.91) | Male | 319 | 0.73 (0.56-0.96) | <65 | 339 | 0.81 (0.62-1.04) | 0 | 179 | 0.64 (0.44-0.93) | Current/former smoker | 458 | 0.70 (0.56-0.86) |
| Female | 263 | 0.78 (0.58-1.04) | ≥65 to <75 | 200 | 0.63 (0.45-0.89) | 1 | 402 | 0.80 (0.63-1.00) | Never smoked | 118 | 1.02 (0.64-1.61) | ||||||||||
| 2020- Herbst- J Clin Oncol | KEYNOTE-010 | NCT01905657 | 2or3 | 1033 | NSCLC | >1 | Pembrolizumab vs. docetaxel | 1033 | 0.69 (0.60-0.80) | Male | 634 | 0.70 (0.58-0.84) | <65 | 604 | 0.62 (0.51-0.75) | 0 | 347 | 0.78 (0.60-1.01) | |||
| Female | 399 | 0.66 (0.52-0.83) | ≥65 | 429 | 0.79 (0.63-1.00) | 1 | 679 | 0.64 (0.54-0.76) | |||||||||||||
| 2017- Carbone-N Engl J Med | CheckMate 026 | NCT02041533 | 3 | 541 | NSCLC | 1 | Nivolumab vs. chemotherapy | 541 | 1.08 (0.87-1.34) | Male | 332 | 0.97 (0.74-1.26) | <65 | 281 | 1.13 (0.83-1.54) | 0 | 178 | 1.11 (0.74-1.66) | Former smoker | 368 | 1.09 (0.84–1.42) |
| Female | 209 | 1.15 (0.79-1.66) | ≥65 | 260 | 1.04 (0.77-1.41) | ≥1 | 362 | 1.02 (0.79-1.32) | Current smoker | 107 | 1.05 (0.63–1.74) | ||||||||||
| Never smoked | 59 | 1.02 (0.54–1.93) | |||||||||||||||||||
| 2017- Govindan-J Clin Oncol | NCT01285609 | 3 | 749 | Squamous | >1 | Ipilimumab+chemotherapy vs. placebo+chemotherapy | 749 | 0.91 (0.77-1.07) | Male | 635 | 0.85 (0.71-1.02) | <65 | 380 | 0.82 (0.64-1.04) | 0 | 259 | 0.99 (0.73-1.33) | Heavy smoker | 656 | 0.88 (0.73-1.05) | |
| Female | 114 | 1.33 (0.84-2.11) | ≥65 to <75 | 298 | 1.06 (0.81-1.37) | 1 | 485 | 0.86 (0.70-1.05) | Former/light/nonsmoker | 83 | 1.19 (0.71-1.99) | ||||||||||
| 2021-Corinne- J Thorac Oncol | PACIFIC | NCT02125461 | 3 | 713 | NSCLC | >1 | Durvalumab vs. placebo | 713 | 0.70 (0.57–0.86) | Male | 500 | 0.75 (0.59–0.96) | <65 | 391 | 0.64 (0.48–0.86) | 0 | 348 | 0.84 (0.62–1.15) | Smoker | 649 | 0.73 (0.59–0.91) |
| Female | 213 | 0.59 (0.40–0.87) | ≥65 | 322 | 0.77 (0.58–1.03) | ≥1 | 365 | 0.59 (0.45–0.77) | Nonsmoker | 64 | 0.42 (0.21–0.82) | ||||||||||
| 2018-Barlesi- Lancet Oncol | JAVELIN lung 200 | NCT02395172 | 3 | 529 | NSCLC | >1 | Avelumab vs. docetaxel | 529 | 0.90 (0.73-1.12) | Male | 367 | 0.83 (0.64-1.08) | <65 | 279 | 0.84 (0.63-1.13) | 0 | 187 | 0.73 (0.50-1.08) | Ever smoker | 444 | 0·83 (0·66–1·04) |
| Female | 162 | 1.08 (0.74-1.59) | ≥65 | 250 | 0.98 (0.71-1.34) | 1 | 342 | 0.99 (0.77-1.28) | Never smoker | 84 | 1·69 (0·97–2·95) | ||||||||||
| 2018- Fehrenbacher -J Thorac Oncol | OAK | NCT02008227 | 3 | 1225 | NSCLC | >1 | Atezolizumab vs. docetaxel | 1225 | 0.80 (0.70-0.92) | Male | 758 | 0.79 (0.66-0.93) | <65 | 661 | 0.84 (0.70-1.01) | 0 | 455 | 0.80 (0.63-1.02) | Current/previous smoker | 1017 | 0·78 (0·67–0·90) |
| Female | 467 | 0.81 (0.65-1.01) | ≥65 | 564 | 0.75 (0.61-0.91) | 1 | 770 | 0.77 (0.65-0.90) | Never smoked | 208 | 0·91 (0·65–1·29) | ||||||||||
| 2018-Gandhi- N Engl J Med | KEYNOTE- 189 | NCT02578680 | 3 | 616 | Nonsquamous | 1 | Pembrolizumab+chemotherapy vs. placebo+chemotherapy | 616 | 0.49 (0.38-0.64) | Male | 363 | 0.70 (0.50-0.99) | <65 | 312 | 0.43 (0.31-0.61) | 0 | 266 | 0.44 (0.28-0.71) | Current/former smoker | 543 | 0.54 (0.41–0.71) |
| Female | 253 | 0.29 (0.19-0.44) | ≥65 | 304 | 0.64 (0.43-0.95) | 1 | 346 | 0.53 (0.39-0.73) | Never smoked | 73 | 0.23 (0.10–0.54) | ||||||||||
| 2018-Paz- Ares-N Engl J Med | KEYNOTE- 407 | NCT02775435 | 3 | 559 | Squamous | 1 | Pembrolizumab+chemotherapy vs. placebo+chemotherapy | 559 | 0.64 (0.49-0.85) | Male | 455 | 0.69 (0.51-0.94) | <65 | 254 | 0.52 (0.34-0.80) | 0 | 163 | 0.54 (0.29-0.98) | |||
| Female | 104 | 0.42 (0.22-0.81) | ≥65 | 305 | 0.74 (0.51-1.07) | 1 | 396 | 0.66 (0.48-0.90) | |||||||||||||
| 2019-Mok- Lancet | KEYNOTE- 042 | NCT02220894 | 3 | 1274 | NSCLC | 1 | Pembrolizumab vs. chemotherapy (PD-L1 TPS ≥ 1%) | 1274 | 0.81 (0.71-0.93) | Male | 902 | 0.80 (0.68-0.94) | <65 | 707 | 0.81 (0.67-0.98) | 0 | 390 | 0.77 (0.58-1.05) | Never | 282 | 1.00 (0.73-1.37) |
| Female | 372 | 0.89 (0.68-1.17) | ≥65 | 567 | 0.82 (0.66-1.01) | 1 | 884 | 0.83 (0.71-0.98) | Former | 721 | 0.71 (0.59-0.86) | ||||||||||
| Current | 271 | 0.95 (0.70-1.29) | |||||||||||||||||||
| 2019-Reck-J Clin Oncol | KEYNOTE- 024 | NCT02142738 | 3 | 305 | NSCLC | 1 | Pembrolizumab vs. platinum-based chemotherapy | 305 | 0.63 (0.47-0.86) | Male | 187 | 0.54 (0.36-0.79) | <65 | 141 | 0.60 (0.38-0.96) | 0 | 107 | 0.78 (0.44-1.37) | Current | 65 | 0.81 (0.41-1.60) |
| Female | 118 | 0.95 (0.56-1.62) | ≥65 | 164 | 0.64 (0.42-0.98) | 1 | 197 | 0.56 (0.39-0.81) | Former | 216 | 0.59 (0.41-0.85) | ||||||||||
| Never | 24 | 0.90 (0.11-7.59) | |||||||||||||||||||
| 2019-ReckM- Lancet Respir Med | IMpower150 | NCT02366143 | 3 | 1202 | Nonsquamous | 1 | ABCP vs. BCP | 800 | 0.76 (0.63-0.93) | Male | 479 | 0.73 (0.57-0.93) | <65 | 441 | 0.78 (0.60-1.00) | 0 | 338 | 0.75 (0.53-1.07) | Never smoker | 159 | 0.66 (0.41-0.85) |
| Female | 321 | 0.82 (0.61-1.12) | 65-74 | 281 | 0.69 (0.49-0.96) | 1 | 456 | 0.75 (0.59-0.94) | Current/previous smoker | 641 | 0.80 (0.65-0.98) | ||||||||||
| ACP vs. BCP | 802 | 0.85 (0.71-1.03) | Male | 480 | 0.82 (0.64-1.04) | <65 | 449 | 0.76 (0.59-0.98) | 0 | 359 | 0.85 (0.61-1.18) | Never smoker | 154 | 0.96 (0.62-1.49) | |||||||
| Female | 322 | 0.88 (0.65-1.19) | 65-74 | 284 | 0.97 (0.71-1.32) | 1 | 440 | 0.84 (0.67-1.06) | Current/previous smoker | 648 | 0.82 (0.66-1.01) | ||||||||||
| 2019-West- Lancet Oncol | IMpower130 | NCT02367781 | 3 | 679 | Nonsquamous | 1 | Atezolizumab+carboplatin+nab-paclitaxel vs. chemotherapy | 679 | 0·79 (0·64–0·98) | Male | 400 | 0.87 (0.66-1.15) | <65 | 341 | 0.79 (0.58-1.08) | 0 | 280 | 0·85 (0·59–1·22) | Never smoker | 65 | 0·55 (0·26–1·19) |
| Female | 279 | 0.66 (0.46-0.93) | ≥65 | 338 | 0·78 (0·58–1·05) | 1 | 397 | 0·77 (0·58–1·00) | Current/previous smoker | 614 | 0·81 (0·65–1·02) | ||||||||||
| 2020-Jotte-J Thorac Oncol | IMpower131 | NCT02367794 | 3 | 1021 | Squamous | 1 | Atezolizumab+carboplatin+nab-paclitaxel vs. carboplatin+nab-paclitaxel | 683 | 0·88 (0·73–1·05) | Male | 557 | 0·91 (0·75–1·12) | <65 | 326 | 0·89 (0·68–1·15) | 0 | 225 | 0·96 (0·69–1·34) | Never smoker | 55 | 0·85 (0·43–1·68) |
| Female | 126 | 0·68 (0·44–1·04) | 65-74 | 279 | 0·84 (0·63–1·13) | 1 | 456 | 0·82 (0·66–1·02) | Current/previous smoker | 627 | 0·87 (0·72–1·05) | ||||||||||
| 2019-Hellmann-N Engl J Med | CheckMate 227 | NCT02477826 | 3 | 1739 | NSCLC | 1 | Nivolumab+ipilimumab vs. chemotherapy | 1166 | 0.73 (0.64–0.84) | Male | 778 | 0.68 (0.57–0.80) | <65 | 611 | 0.70 (0.58–0.85) | 0 | 395 | 0.70 (0.54–0.89) | Never smoker | 157 | 0.96 (0.66–1.41) |
| Female | 388 | 0.89 (0.70–1.12) | ≥65 | 442 | 0.76 (0.61–0.95) | 1 | 763 | 0.77 (0.65–0.90) | Current/previous smoker | 996 | 0.72 (0.62–0.84) | ||||||||||
| 2020-Herbst -N Engl J Med | IMpower110 | NCT02409342 | 3 | 572 | NSCLC | 1 | Atezolizumab vs. chemotherapy (high PD-L1 expression) | 205 | 0.59 (0.40–0.89) | Male | 143 | 0.57 (0.35–0.93) | <65 | 102 | 0.59 (0.34–1.04) | 0 | 73 | 0.42 (0.20–0.92) | Never | 24 | 1.83 (0.63–5.31) |
| Female | 62 | 0.69 (0.34–1.39) | 65-74 | 80 | 0.63 (0.34–1.19) | 1 | 132 | 0.69 (0.43–1.10) | Current | 49 | 0.35 (0.14–0.88) | ||||||||||
| Previous | 132 | 0.60 (0.36–1.00) | |||||||||||||||||||
| 2021-Nishio-J Clin Oncol | IMpower132 | NCT02657434 | 3 | 578 | Nonsquamous | 1 | Atezolizumab+carboplatin/cisplatin+pemetrexed vs. carboplatin/cisplatin+pemetrexed | 578 | 0.86 (0.71, 1.06) | Male | 384 | 0.93 (0.73, 1.18) | <65 | 321 | 0.88 (0.67, 1.16) | 0 | 240 | 0.76 (0.55, 1.04) | Never smoker | 67 | 0.78 (0.42, 1.43) |
| Female | 194 | 0.76 (0.54, 1.09) | ≥65 | 257 | 0.84 (0.63, 1.13) | 1 | 336 | 0.99 (0.76, 1.27) | Current/former smoker | 511 | 0.89 (0.72, 1.09) |
Abbreviations: HR = hazard ratio; OS = overall survival; ABCP =atezolizumab plus bevacizumab plus carboplatin plus paclitaxel; ACP =atezolizumab plus carboplatin plus paclitaxel; BCP =bevacizumab plus carboplatin plus paclitaxel.