Approved drugs in lung oncology, 2000–2020

Chemical nameLine of therapyPhase I trial
(first author [ref.])
Trial leading to approval (first author [ref.])Sample sizeEMA approval dateApproval trial phaseHistologyClassMonoclonal antibodyRoute of administrationPrimary end-point trial leading to approval
DocetaxelSecondExtra [13]Shepherd [14]n=1036 February 2000IIINSCLCChemotherapyNoi.v.MOS
Pemetrexed SecondMcDonald [15]Hanna [16]n=57122 September 2004IIInsNSCLC#ChemotherapyNoi.v.MOS
ErlotinibSecondHidalgo [17]Shepherd [18]n=73127 June 2005IIINSCLCTargeted agentNoOralMOS
GefitinibAnyBaselga [19]Mok [20]n=12171 July 2009IIInsNSCLCTargeted agentNoOralPFS
ErlotinibFirstHidalgo [17]Rosell [21]n=1741 November 2011IIInsNSCLCTargeted agentNoOralPFS
CrizotinibSecondKwak [22]Shaw [11]n=34724 October 2012IIIROS1/ALK+NSCLC+Targeted agentNoOralPFS
AfatinibFirstYap [23]Sequist [24]n=34525 September 2013IIIEGFR+nsNSCLCTargeted agentNoOralPFS
CeritinibSecondShaw [25]Shaw [26]n=2318 May 2015IIIALK+NSCLCTargeted agentNoOralPFS
NivolumabSecondBrahmer [27]Brahmer [28]n=27220 July 2015IIISqNSCLCImmune checkpointYesi.v.MOS
CrizotinibFirstKwak [22]Solomon [29]n=34324 November 2015IIIROS1/ALK+NSCLC+Targeted agentNoOralPFS
OsimertinibSecondCross [30]Mok [31]n=4193 February 2016IIIEGFR M+NSCLCTargeted agentNoOralPFS
NivolumabSecondBrahmer [27]Borghaei [32]n=5826 April 2016IIInsNSCLCImmune checkpointYesi.v.MOS
AfatinibSecondYap [23]Thongprasert [33]n=607 April 2016IIIEGFR+NSCLCTargeted agentNoOralORR
PembrolizumabSecondGaron [34]Herbst [35]n=10342 August 2016IIIPD-L1 >1%+NSCLCImmune checkpointYesi.v.MOS PFS§
PembrolizumabFirstGaron [34]Reck [36]n=30531 January 2017IIIPD-L1 >50% NSCLCImmune checkpointYesi.v.PFS
AlectinibSecondSeto [37]Shaw [38]n=8721 February 2017IIALK+NSCLCTargeted agentNoOralORR
Dabrafenib/trametinibAnyFalchook [39]Planchard [40]n=363 April 2017IIBRAf V600E+NSCLCTargeted agentNoOralORR
AtezolizumabSecondHerbst [41]Rittmeyer [42]n=112522 September 2017IIINSCLCImmune checkpointYesi.v.MOSƒ
AlectinibFirstSeto [37]Peters [43]n=30321 December 2017IIIALK+NSCLCTargeted agentNoOralPFS
OsimertinibFirstCross [30]Soria [44]n=5568 June 2018IIIEGFR M+NSCLCTargeted agentNoOralPFS
DurvalumabConsolidationAntonia [45]Antonia [46]n=70927 July 2018IIINSCLCImmune checkpointYesi.v.MOS PFS§
BrigatinibSecondGettinger [47]Camidge [48]n=27527 November 2018IIIALK+ NSCLCTargeted agentNoOralPFS
DacomitinibFirstTakahashi [49]Wu [50]n=4523 April 2019IIIEGFR M+NSCLCTargeted agentNoOralPFS
LorlatinibSecondShaw [51]Solomon [52]n=2767 May 2019IIALK+NSCLCTargeted agentNoOralORRƒ
LarotrectinibAnyDrilon [53]Drilon [53]n=5523 September 2019IINTRK+NSCLCTargeted agentNoOralORR
BrigatinibFirstGettinger [47]Hubert [54]n=2226 April 2020IIIALK+ NSCLCTargeted agentNoOralORR

#: first approval was granted for any NSCLC but after subgroup analyses of three trials employing pemetrexed the approval was restricted to nsNSCLC for lack of efficiency in squamous NSCLC [62]. : although later approved as a targeted agent, the drug was first approved for any NSCLC without any mandatory companion diagnostic to detect a targetable mutation.

+: Pfizer [55].

§: for details please refer to full publication as alpha was split applying different statistical plans. ƒ: and intracranial tumour response. EMA: European Medicines Agency; NSCLC: nonsmall cell lung cancer; MOS: median overall survival; nsNSCLC: nonsquamous nonsmall cell lung cancer; PFS: progression free survival; ALK: anaplastic lymphoma kinase; EGFR: epidermal growth factor receptor; SqNSCLC: squamous nonsmall cell lung cancer; EGFR M+NSCLC: EGFR mutation positive NSCLC; ORR: objective response rate according to RECIST 1.1