An Exceptional Responder to Nivolumab in Metastatic Non-Small-Cell Lung Cancer: A Case Report and Literature Review of Long-Term Survivors

Table 1

Long-term outcomes of patients treated with immune checkpoint inhibitors in metastatic NSCLC.

	Characteristics	Outcomes and exceptional responders
Clinical trials (5 yr data)
Phase 1 (CA 209-003)
Nivolumab; 2nd line; Ref. [6]	129 patients; Median follow-up: 58 m	Median OS 9.9 m; 5-year OS 16% (43% for PDL‐1 ≥ 50%); For 5-year survivors: 14/16 current or former smokers, 10/16 had received prior RT, 12/16 no further tx after stopping Nivo and without PD; in 7, ≥50% in 5, <1% in 3 pts
Phase Ib (Keynote 001)
Pembrolizumab; 1st line or later; Ref. [8]	101 tx naïve; 449 previously treated; Median follow-up: 60.6 m	Treatment naïve: Median DOR 16.8 m; CR 3% (3 patients); Median OS 22.3 m; 5-year OS 23.2% (29.6% for ); Previously treated: Median DOR 38.9 m; CR 1.1% (5 patients); Median OS 10.5 m (15.5 m for ); 5-year OS 15.6% (25% for )
Clinical trials (3 yr data)
Phase III (CheckMate 017, 057)
Nivolumab vs. Doc; 2nd line; Ref. [35]	854 patients; Median follow-up: 40.3 m	Median DOR 23.8 m; CR 6% for those alive at 3 years; 3-year OS: 17% (vs. 8% Doc), 8% (vs. 2%) for patients with liver metastases
Phase III (Keynote 010)
Pembrolizumab vs. Doc; 2nd line or later; Ref. [49]	1033 patients; Median follow-up: 42.6 m	: Median OS 16.9 m (vs. 8.2 m Doc); 3-year OS: 35% (vs. 13% Doc); : Median OS 11.8 m (vs. 8.4 m Doc); 3-year OS: 23% (vs. 11% Doc)
Phase II (POPLAR)
Atezolizumab vs. Doc; 2nd line; Ref. [50]	287 patients; Minimum 3-year follow-up	Median DOR: 22.3 m (vs. 7.2 m docetaxel); 3-year OS: ITT 16.6% (vs. 10% docetaxel); IHC TC3 or IC3 37.5% (vs. 14.9%); IHC TC 2/3 or IC 2/3 21.2% (vs. 9.9%)
Case reports
Nivolumab; 3rd line; Ref. [28]	67 male; squamous cell ca; TMB 87-91 Mut/Mb	Nivolumab-induced pneumonitis after 3 doses; following discontinuation of the drug, the patient continued to have complete remission for 14 months
Nivolumab; 2nd line; Ref. [29]	80 male; squamous cell ca; RT (3 months prior to Nivo)	Radiation-induced pneumonitis; CR after 6 cycles, ongoing after 2 years of continuous nivolumab
Nivolumab; 2nd line; Ref. [31]	47 male; adenocarcinoma; Current smoker; SBRT to LNs while on Nivo	PR after 6 cycles; CR after 13 cycles (10 weeks after RT); Nivo discontinued after cycle 17 due to pancreatitis; still in CR almost 2 years since discontinuation

Abbreviations: OS—overall survival; m—months; tx—treatment; DOR—duration of response; CR—complete response; PD—progressive disease; ITT—intention to treat; Nivo—nivolumab; doc—docetaxel; LN—lymph node; ca—carcinoma; NSCLC—non-small-cell lung cancer; RT—radiotherapy; SBRT—stereotactic body radiation therapy; IHC—immunohistochemistry; TC—tumor cells; IC—tumor-infiltrating immune cells; Mut/Mb—mutations per megabase; PDL-1—programmed death ligand-1.