Real-World, Long-Term Outcomes of Nivolumab Therapy for Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck and Impact of the Magnitude of Best Overall Response: A Retrospective Multicenter Study of 88 Patients
Abstract
:Simple Summary
Abstract
1. Introduction
2. Results
2.1. Patient Characteristics
2.2. Treatment Outcomes
2.3. Immune-Related Adverse Events
2.4. Impact of Background Factors on Patient Survival
2.5. Survival According to Best Overall Response
3. Discussion
4. Materials and Methods
4.1. Patients
4.2. Treatment and Follow-up
4.3. Outcomes
4.4. Immune-Relate Adverse Events
4.5. Statistical Analysis
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Characteristic | N = 88 | (%) |
---|---|---|
Sex | ||
Male | 71 | (81) |
Female | 17 | (19) |
Age | ||
<65 years | 39 | (44) |
≥65 years | 49 | (56) |
ECOG performance status | ||
0 | 59 | (67) |
1 | 24 | (27) |
≥2 | 5 | (6) |
Primary site | ||
Nasopharynx | 10 | (11) |
Oropharynx | 19 | (22) |
p16-positive | 8 | (9) |
Hypopharynx | 21 | (24) |
Larynx | 10 | (11) |
Oral cavity | 17 | (19) |
Paranasal sinus | 6 | (7) |
Salivary gland | 2 | (2) |
External auditory canal | 3 | (3) |
Histology | ||
Squamous cell carcinoma | 88 | (100) |
Smoking | ||
Ever | 61 | (69) |
Never | 26 | (30) |
Unknown | 1 | (1) |
Alcohol | ||
Ever | 69 | (78) |
Never | 17 | (19) |
Unknown | 2 | (2) |
Distant metastasis | ||
Present | 26 | (30) |
Absent | 52 | (59) |
Previous exposure to cetuximab | ||
Yes | 30 | (34) |
No | 58 | (66) |
Platinum refractoriness a | ||
Yes | 28 | (32) |
No | 60 | (68) |
Previous radiotherapy | ||
Yes | 17 | (19) |
No | 71 | (81) |
Previous number of chemotherapy regimens b | ||
1 | 37 | (42) |
2 | 35 | (40) |
≥3 | 16 | (18) |
PD-L1 expression | (0) | |
Positive (≥1%) | 37 | (42) |
Negative (<1%) | 7 | (8) |
Unknown | 44 | (50) |
Institution | (0) | |
TMU | 41 | (47) |
IUHW | 24 | (27) |
KU | 15 | (17) |
TMU/HMC | 8 | (9) |
Best Overall Response | N = 88 | (%) |
---|---|---|
Complete response (CR) | 5 | (6) |
Partial response (PR) | 11 | (13) |
Stable disease (SD) | 26 | (30) |
Progressive disease (PD) | 46 | (52) |
Response rate (CR + PR) | 16 | (18) |
Disease control rate (CR + PR + SD) | 42 | (48) |
Immune-Related Adverse Events | Any Grade | Grade 3–5 |
---|---|---|
Interstitial lung disease | 13 | 5 |
Thyroid dysfunction | 8 | 0 |
Liver dysfunction | 5 | 3 |
Skin disorders | 4 | 1 |
Enteritis | 1 | 1 |
Adrenal insufficiency | 1 | 0 |
Infusion reactions | 1 | 0 |
Myositis | 1 | 0 |
Parathyroid dysfunction | 1 | 0 |
Pituitary dysfunction | 1 | 0 |
Renal dysfunction | 1 | 0 |
Rheumatoid arthritis | 1 | 0 |
Total | 38 | 10 |
(29 patients) | (9 patients) |
Overall Survival | Progression-Free Survival | |||||||
---|---|---|---|---|---|---|---|---|
Background Factors | Crude | Adjusted a | Crude | Adjusted a | ||||
HR (95% CI) | p-Value | HR (95% CI) | p-Value | HR (95% CI) | p-Value | HR (95% CI) | p-Value | |
Sex | ||||||||
Male (Ref. Female) | 1.03 (0.54–1.98) | 0.922 | 0.54 (0.22–1.34) | 0.185 | 1.19 (0.64–2.23) | 0.581 | 0.64 (0.28–1.45) | 0.281 |
Age | ||||||||
≥65 years (Ref. < 65 years) | 1.37 (0.83–2.24) | 0.216 | 1.27 (0.76–2.14) | 0.362 | 0.97 (0.61–1.56) | 0.914 | 0.79 (0.48–1.30) | 0.354 |
ECOG performance status | ||||||||
2–3 (Ref. 0–1) | 16.91 (5.69–50.32) | <0.001 | 20.07 (6.35–63.39) | <0.001 | 6.00 (2.31–15.53) | <0.001 | 7.87 (2.77–22.35) | <0.001 |
Smoking | ||||||||
Ever (Ref. Never) | 1.17 (0.67–2.04) | 0.583 | 0.86 (0.42–1.75) | 0.669 | 1.16 (0.69–1.94) | 0.587 | 0.86 (0.45–1.66) | 0.660 |
Alcohol consumption | ||||||||
Ever (Ref. Never) | 1.51 (0.77–2.98) | 0.230 | 1.64 (0.67–4.03) | 0.278 | 1.61 (0.84–3.08) | 0.149 | 1.60 (0.71–3.60) | 0.257 |
Distant metastasis | ||||||||
Present (Ref. Absent) | 0.94 (0.57–1.55) | 0.818 | 0.95 (0.59–1.53) | 0.844 | ||||
Previous exposure to cetuximab | ||||||||
Yes (Ref. No) | 1.43 (0.84–2.45) | 0.188 | 1.71 (1.02–2.88) | 0.042 | ||||
Platinum refractoriness | ||||||||
Yes (Ref. No) | 1.69 (0.98–2.91) | 0.060 | 1.55 (0.80–3.01) | 0.196 | 1.80 (1.07–3.05) | 0.028 | 1.78 (0.96–3.30) | 0.067 |
Previous radiotherapy | ||||||||
Yes (Ref. No) | 1.05 (0.56–1.96) | 0.883 | 0.83 (0.46–1.50) | 0.539 | ||||
Previous number of chemotherapy regimens | ||||||||
two or more (Ref. 1) | 1.05 (0.63–1.73) | 0.860 | 1.12 (0.70–1.80) | 0.640 | ||||
PD-L1 expression | ||||||||
Positive (Ref. Negative) | 0.58 (0.25–1.35) | 0.203 | 0.50 (0.21–1.19) | 0.117 | ||||
p16 expression | ||||||||
Positive (Ref. Negative or Unknown) | 0.66 (0.28–1.53) | 0.332 | 0.76 (0.35–1.66) | 0.490 | ||||
Immune-related adverse events | ||||||||
Yes (Ref. No) | 0.60 (0.35–1.03) | 0.065 | 0.54 (0.31–0.96) | 0.036 | 0.59 (0.35–0.98) | 0.040 | 0.53 (0.31–0.92) | 0.023 |
Overall Survival | |||||||||||
Crude | |||||||||||
N = 88 | (%) | median (months) | (95% CI) | 1-year OS (%) | (95% CI) | 2-year OS (%) | (95% CI) | HR | (95% CI) | p-value | |
CR/PR | 16 | (18) | NR | 94 | (63–99) | 94 | (63–99) | 0.02 | (0.003–0.15) | <0.001 | |
SD | 26 | (30) | 11.1 | (8.6–20.7) | 46 | (27–64) | 27 | (12–45) | 0.37 | (0.21–0.65) | 0.001 |
PD | 46 | (52) | 6.4 | (3.3–9.0) | 17 | (8–30) | 0 | (NA-NA) | 1 (reference) | ||
Progression-Free Survival | |||||||||||
Crude | |||||||||||
N = 88 | (%) | median (months) | (95% CI) | 1-year PFS (%) | (95% CI) | 2-year PFS (%) | (95% CI) | HR | (95% CI) | p-value | |
CR/PR | 16 | (18) | NR | (22.1-NA) | 88 | (59–97) | 78 | (44–93) | 0.02 | (0.005–0.06) | <0.001 |
SD | 26 | (30) | 7.0 | (4.3–12.4) | 34 | (16–52) | 17 | (5–34) | 0.10 | (0.05–0.22) | <0.001 |
PD | 46 | (52) | 1.5 | (1.1–2.5) | NA | (NA-NA) | 0 | (NA-NA) | 1 (reference) |
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Matsuki, T.; Okamoto, I.; Fushimi, C.; Takahashi, H.; Okada, T.; Kondo, T.; Sato, H.; Ito, T.; Tokashiki, K.; Tsukahara, K.; et al. Real-World, Long-Term Outcomes of Nivolumab Therapy for Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck and Impact of the Magnitude of Best Overall Response: A Retrospective Multicenter Study of 88 Patients. Cancers 2020, 12, 3427. https://doi.org/10.3390/cancers12113427
Matsuki T, Okamoto I, Fushimi C, Takahashi H, Okada T, Kondo T, Sato H, Ito T, Tokashiki K, Tsukahara K, et al. Real-World, Long-Term Outcomes of Nivolumab Therapy for Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck and Impact of the Magnitude of Best Overall Response: A Retrospective Multicenter Study of 88 Patients. Cancers. 2020; 12(11):3427. https://doi.org/10.3390/cancers12113427
Chicago/Turabian StyleMatsuki, Takashi, Isaku Okamoto, Chihiro Fushimi, Hideaki Takahashi, Takuro Okada, Takahito Kondo, Hiroki Sato, Tatsuya Ito, Kunihiko Tokashiki, Kiyoaki Tsukahara, and et al. 2020. "Real-World, Long-Term Outcomes of Nivolumab Therapy for Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck and Impact of the Magnitude of Best Overall Response: A Retrospective Multicenter Study of 88 Patients" Cancers 12, no. 11: 3427. https://doi.org/10.3390/cancers12113427