Table Info

Table 3.

Immune checkpoint inhibitors + chemotherapy ± anti-VEGF antibodies for EGFR mutant NSCLC

Treatment	Study name	Setting	Drugs	Phase	Efficacy	AEs	References
Chemotherapy + IO	CheckMate012	2nd	Nivolumab + platinum doublet	I	EGFR mutated vs. wild type, ORR: 17% vs. 47%, PFS: 4.8 months vs. 7.5 months, OS: 20.5 months vs. 24.5 months.	G3–4: 50%, G5: 0%. (All patients, not only EGFR).	[50]
	IMpower130	2nd	Comparing CBDCA + nab-PTX + atezolizumab with CBDCA + nab-PTX	III	In the subgroup of EGFR/ALK, the mPFS was 7.0 months vs. 6.0 months (HR 0.75, 95% CI: 0.36–1.54).	G3–4: 81% in the combination arm. (All patients, not only EGFR).	[51]
	CheckMate722	2nd	Nivolumab plus chemotherapy vs. chemotherapy	III	PFS: 5.6 months in the nivolumab plus chemotherapy group and 5.4 months in the chemotherapy group.	G3–4: 45% in nivolumab-based therapy and 29% in chemotherapy.	[55]
	KEYNOTE789	2nd	Pembrolizumab plus chemotherapy vs. chemotherapy	III	PFS: 5.6 months in the pembrolizumab plus chemotherapy group and 5.5 months in the chemotherapy group.	G3 ≤ TRAE; 43.7%, irAE 4.5% in combination arm.	[56]
Chemotherapy + dual-IO	ILLUMINATE	2nd	Durvalumab and tremelimumab plus platinum-pemetrexed	II	The ORR was 42% in cohort 1 and 35% in cohort 2, with mPFS of 6.5 months and 4.9 months.	G3–4 colitis 8%, hepatitis 4%, ILD 1%.	[54]
Chemotherapy + IO + anti-VEGF	IMpower150	2nd	Atezolizumab, bevacizumab, carboplatin-paclitaxel (CP). Control arm: BCP, study arm: ACP, ABCP	III	ORR 70.6% for ABCP, 35.6% for ACP, 41.9% for BCP.	G3–4: 64% of ABCP, 68% of ACP, and 64% of BCP.	[57, 58]
Chemotherapy + IO + anti-VEGF	ORIENT	2nd	Scintilimab, IBI305 (bevacizumab biosimilar), pemetrexed + cisplatin (PC). Arm A: SIPC, arm B: SPC, arm C: PC→S	III	Confirmed ORR were 43.9%, 33.1%, and 25.2% in arm A, B, and C, PFS 6.9 months for arm A, 5.5 months for arm B, 4.3 months for arm C.	Grade ≥ 3 treatment-emergent AEs were 54.7% (arm A), 39.3% (arm B), and 51.0% (arm C).	[55]
Chemotherapy + IO + anti-VEGF	IMpower151	2nd	Atezolizumab, bevacizumab, carboplatin-pemetrexed. Control arm: bevacizumab + carboplatin-pemetrexed, study arm: atezolizumab + carboplatin-pemetrexed, atezolizumab + bevacizumab + carboplatin-pemetrexed. Over half of the patients had EGFR/ALK	III	In the subgroup of EGFR/ALK, the mPFS was 8.5 months (95% CI: 6.9–10.3) for atezolizumab + bevacizumab + carboplatin-pemetrexed and 8.3 months (95% CI: 6.9–10.1) for bevacizumab + carboplatin-pemetrexed (HR 0.86, 95% CI: 0.55–1.19).	G3–4: 67.1% of ABCP, G5 5.9% in ABCP.	[59]

irAE: immune-related adverse events; CP: carboplatin-paclitaxel; BCP: bevacizumab carboplatin-paclitaxel; ACP: atezolizumab carboplatin-paclitaxel; PC: pemetrexed + cisplatin; SIPC: scintilimab + IBI305 + pemetrexed + cisplatin; SPC: scintilimab + pemetrexed + cisplatin; EGFR: epidermal growth factor receptor; TRAE: treatment related adverse event; mPFS: median progression free survival; ORR: objective response rate; IO: immune-oncology; OS: overall survival; CBDCA: carboplatin; nab-PTX: nanoparticle albumin-bound paclitaxel; VEGF: vascular endothelial growth factor; NSCLC: non-small cell lung cancer; HR: hazard ratio; CI: confidence intervals; TRAE: treatment related adverse event; ILD: interstitial lung disease; ALK: anaplastic lymphoma kinase. PC→S: pemetrexed + cisplatin → sincilimab

Declarations

Author contributions

KA, TS, AI, TH, YG, NH, and MK: Writing—review & editing. KI: Writing—review & editing, Supervision. YO: Conceptualization, Data curation, Writing—review & editing. All authors read and approved the submitted version.

Conflicts of interest

YO reports personal fees from Bristol Myers Squibb, Eli Lilly, Takeda, Daiichi Sankyo, AstraZeneca, Chugai Pharma, Amgen, and Novartis, and personal fees from Taiho outside the submitted work. YG reports personal fees from Bristol Myers Squibb, Eli Lilly, Takeda, AstraZeneca, Chugai Pharma, Taiho, and Boehringer Ingelheim outside the submitted work. NH received a research grant from Boehringer Ingelheim and lecture fees from GlaxoSmithKline, AstraZeneca, Novartis, and Boehringer Ingelheim, outside the submitted work. MK received personal fees from Bristol Myers Squibb, Eli Lilly, Takeda, Daiichi Sankyo, AstraZeneca, Chugai Pharma, MSD, and Taiho outside the submitted work. KI reports personal fees from GSK, MSD, Sanofi, AstraZeneca, and Chugai Pharmaceutical Co., and he received research grants from Chugai Pharmaceutical Co. and Taiho Pharmaceutical Co. The other authors declare that they have no conflict of interest.

Ethical approval

Not applicable.

Consent to participate

Not applicable.

Consent to publication

Not applicable.

Availability of data and materials

Not applicable.

Funding

Not applicable.

Copyright

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