Immunotherapy Breakthroughs in the Treatment of Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma
Abstract
:Simple Summary
Abstract
1. Introduction
2. KEYNOTE-012 Phase 1b Study: Anti-Tumor Activity of Pembrolizumab
3. Phase II and III Second Line Studies and Beyond
3.1. Phase II Studies
3.2. Phase III Studies
3.2.1. Nivolumab and the CHECKMATE-141 Study
Studies | IO Agent | Phase | Nb of Patients | ORR (95%CI) | DOR Median Mo (Extremes) | Grade ≥ 3 Related Toxicities | PFS Median Mo (95%CI) | OS Median Mo (95%CI) | 1-Year OS | Remarks |
---|---|---|---|---|---|---|---|---|---|---|
KEYNOTE-012 [6] | P | Ib Initial cohort | 60 | 18% | 53 weeks | 17% | 2 (1–4) | 13 (5-NR) | PD-L1 positive | |
KEYNOTE-012 [7] | P | Ib expansion cohort | 132 | 18% (12–26) | NR (2–11) | 9% | 2 (2–2.2) | 8 (6–10) | Wathever PD-L1, HPV stat. | |
KEYNOTE-012 [8] | P | Ib: pooled | 192 | 18% (13–24) | NR (2+–30+) | 13% | 8 (6–10) | 38% | Long term FUP | |
Study 1108 [14] | D | Ib-II | 62 | 11% (4–21) | 6 resp. ≥12 mo | 8% | 8.9 (5.4–18.8) | 42% | 79% of pt ≥3rd line | |
KEYNOTE-055 [9] | P | II | 171 | 16% (11–23) | 8 (2+–12+) | 15% | 2.1 (2.1–2.1) | 8 (6–11) | Platinum Cetuximab Refractory | |
HAWK [10] | D | II | 112 | 16.2% (9.9–24.4) | 10.3 mo | 8% | 2.1 (1.9–3.7) | 7.1 (4.9–9.9) | 33.6% | PD-L1 high |
CONDOR [11] | D T | II randomized | 267 | D + T: 7.8% D: 9.2% T: 1.6% | 9.4(4.9-NR) | 15.8% 12.3% 16.9% | 2.0 1.9 1.9 | 7.6(4.9–10.6 6(4–11.3) 5.5(3.9–7) | 37% 36% 24% | PD-L1 Low/neg. |
Studies | Number of Patients | OS: Median Mo (95%CI) | 1-Year OS (95% CI) | 2-Year OS (95%CI) | PFS Median Mo (95% CI) | ORR (95% CI) | Related Grade ≥ 3 Toxicities |
---|---|---|---|---|---|---|---|
CHECKMATE-141 [13,15] | N: 240 IC:121 | N: 7.5 (5.5–9.1) IC: 5.1 (4.0–6.0) HR, 0.70 (0.51–0.96) * p = 0.01 | N: 36% (28.5–43.4) IC: 16.6% (8.6–26.8) | N: 16.9% (12.4–22) IC: 6.0% (2.7–11.3) | N: 2.0 (1.9–2.1) IC: 2.3 (1.9–3.1) HR, 0.89 (0.7–1.13) p = 0.32 | N: 13.3% (9.3–18.3) mDOR: 9.7 mo IC: 5.8% (2.4–11.6) mDOR: 4.0 mo | N: 13.1% IC: 35.1% |
KEYNOTE-040 [16] | P: 247 IC: 248 | P: 8.4 (6.4–9.4) IC: 6.9 (5.9–8.0) HR, 0.80 (0.65–0.98) p = 0.0161 | P: 37.0% (31.0–43.1) IC: 26.5%(21.2–32.2) | P: 2.1 (2.1–2.3) IC: 2.3 (2.1–2.8) | P: 14.6% (10.4–19.6) mDOR: 18.4 mo IC: 10.6% (6.6–14.5) mDOR: 5.0 mo p = 0.061 | P: 13% IC: 36% | |
EAGLE [17] | D: 240 D + T: 247 SoC: 249 | D: 7.6 (6.1–9.8) D + T: 6.5 (5.5–8.2) SoC: 8.3 (7.3–9.2) D vs. SoC: HR, 0.88 (0.72–1.08) p = 0.20 D + T vs. SoC: HR 1.04 (0.85–1.26) p = 0.76 | D: 37% (30.9–43.1) D + T: 30.4% (24.7–36.3) SoC: 30.5% (24.7–36.4) | D: 18.4% (13.3–24.1) D + T: 13.3% (8.9–18.6) SoC: 10.3% (5.7–16.5) | D: 2.1 (1.9–3.0) D + T: 2.0 (1.9–2.3) SOC: 3.7 (3.1–3.7) | D: 17.9% (13.3–23.4), mDOR: 12.9 mo D + T: 18.2% (13.6–23.6), mDOR: 7.4 mo SoC: 17.3% (12.8–22.5), mDOR: 3.7 mo | D: 10.1% D + T: 16.3% SoC: 24.2% |
3.2.2. Pembrolizumab and KEYNOTE-040 Study
3.2.3. Durvalumab with or without Tremelimumab vs. Standard of Care: the EAGLE Study
3.3. Conclusions for Platinum-Resistant Patients
4. First Line Studies: Platinum Sensitive Patients
4.1. Pembrolizumab (P) or Pembrolizumab + Chemotherapy (C: platinum + 5Fu) vs. EXTREME: KEYNOTE-048 Study
4.1.1. Pembrolizumab vs. EXTREME
4.1.2. Pembrolizumab (P) + Platinum/5Fu (C) vs. EXTREME
4.1.3. KEYNOTE-048 Study Conclusion
4.2. Studies Combining an Anti-PD-L1 with an Anti-CTLA-4
4.2.1. Nivolumab + Ipilimumab vs. EXTREME: CHECKMATE-651 Study (NCT02741570)
4.2.2. Durvalumab + Tremelimumab vs. Durvalumab vs. EXTREME: the KESTREL Study (NCT02551159)
5. Future Developments
5.1. New Immunotherapies and Combinations
5.1.1. GSK609: T Cells Inducible Co-Stimulatory Receptor (ICOS) Agonist
Study | IO Agents + Targeted Therapy | Pts Characteristics. | Nb of Pts | ORR (95%CI) | DCR (95%CI) | PFS Median (95% CI) | OS Median (95%CI) | Related Grade ≥ 3 Toxicity | Consecutive Phase III |
---|---|---|---|---|---|---|---|---|---|
INDUCE-1 NCT02723955 [49] | GSK 609 + pembro. | anti-PD-(L)1 naïve pretreated: 52% | 34 | 24% (10.7–41.2) | 68% (49.5–82.6) | 4.2 mo (2.4–6.2) | 13.1 mo (6.7–20) | 6% | INDUCE-3: Pembro +/− GSK609 INDUCE-4: Pembro + CT+/− GSK609 |
NCT02643550 Expansion cohort 2 [50] | Monalizumab + Cetuximab | Platinum and Anti-PD-(L)1 pretreated | 40 | 20% (10.5–34.8) | 57.5% | 42% 2% related to monalizumab | INTERLINK-1: cetuximab +/− monalizumab | ||
NCT02501096 [51] | Pembro. + lenvatinib | HNSCC cohort Phase II ≤2 prior lines | 22 | 46% (24.4–67.8) | 90.9% | 4.7 mo (4.0–9.8) | 67% | LEAP-010 study NCT04199104 |
5.1.2. Monalizumab
Monalizumab alone and in combination with durvalumab: cohort I1 and I2 of the UPSTREAM trial (NCT03088059)
Monalizumab and Cetuximab
5.2. Immunotherapy and Targeted Therapies
6. Conclusions
Funding
Conflicts of Interest
References
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Nb of Pts | All pts (ITT) | CPS ≥ 1 | CPS ≥ 20 | CPS: 1–19 | CPS < 1 | ||||||
---|---|---|---|---|---|---|---|---|---|---|---|
P | EXTREME | P | EXTREME | P | EXTREME | P | EXTREME | P | EXTREME | ||
301 | 300 | 257 | 255 | 133 | 122 | 124 | 133 | 44 | 45 | ||
OS | med. | 11.5 | 10.7 | 12.3 | 10.3 | 14.8 | 10.7 | 10.8 | 10.1 | 7.9 | 11.3 |
HR (95% CI) | 0.83 (0.70–0.99) p = 0.019 | 0.74 (0.61–0.90) p = 0.00133 | 0.58 (0.44–0.78) p = 0.00010 | 0.86 (0.66–1.12) p = 0.1282 | 1.51(0.96–2.37) p = 0.96 | ||||||
2-year | 27% | 18.8% | 28.9% | 17.4% | 35.3% | 19.1% | 20.5% | 19.0% | 15.9% | 26.7% | |
PFS | med. | 2.3 | 5.2 | 3.2 | 5.0 | 3.4 | 5.3 | 2.2 | 4.9 | 2.1 | 6.2 |
HR (95% CI) | 1.29 (1.09–1.53) p = 0.998 | 1.13 (0.94–1.36) p = 0.895 | 0.99 (0.76–1.29) p = 0.4679 | 1.25 (0.96–1.61) p = 0.95 | 4.31 (2.63–7.08) p = 1.00 | ||||||
1-year | 17.6% | 15% | 20.6% | 13.6% | 23.5% | 15.1% | 24.2% § | 41.4% § | 11.4% § | 56% § | |
RESPONSE | ORR | 16.9% | 36.0% | 19.1% | 34.9% | 23.3% | 36.1% | 14.5% | 33.8% | 4.5% | 42.2% |
SD | 27.2% | 34.0% | 28.0% | 32.9% | 30.1% | 35.2% | |||||
PD | 40.5% | 12.3% | 38.9% | 12.9% | 31.6% | 9.8% | |||||
DOR | 22.6 (1.5–43) | 4.5 (1.2–38.7+) | 23.4 (1.5–43+) | 4.5 (1.2–38.7+) | 22.6 (2.7–43+) | 4.2 (1.2–31.5) | NR (1.5+–38.9+) | 5.0 (1.4+–38.7+) | 2.6 (2.2–3.0) | 7.8 (2.0–38.6+) | |
≥6 mo. | 77.8% | 38.8% | 81.1% | 36% | 83.5% | 34.8% | 76.5% | 36.6% | 0% | 52.7% |
Nb of Pts | All pts (ITT) | CPS ≥ 1 | CPS ≥ 20 | CPS: 1–19 | CPS < 1 | ||||||
---|---|---|---|---|---|---|---|---|---|---|---|
P + C | EXTREME | P + C | EXTREME | P + C | EXTREME | P + C | EXTREME | P + C | EXTREME | ||
281 | 278 | 242 | 235 | 126 | 110 | 116 | 125 | 39 | 43 | ||
OS | med. | 13.0 | 10.7 | 13.6 | 10.4 | 14.7 | 11.0 | 12.7 | 9.9 | 11.3 | 10.7 |
HR (95% CI) | 0.72 (0.60–0.87) p = 0.00025 | 0.65 (0.53–0.80) p = 0.00002 | 0.60 (0.45–0.82) p = 0.00044 | 0.71 (0.54–0.94) p = 0.00726 | 1.21 (0.76–1.94) p = 0.78 | ||||||
2-year | 29.4% | 18.2% | 30.8% | 16.8% | 35.4% | 19.4% | 25.9% | 14.5% | 20.5% | 25.6% | |
PFS | med. | 2.3 | 5.2 | 5.1 | 5.0 | 5.8 | 5.3 | 4.9 | 4.9 | 4.7 | 6.2 |
HR (95% CI) | 1.29 (1.09–1.53) p = 0.998 | 0.84 (0.69–1.02) p = 0.0369 | 0.76 (0.58–1.01) p = 0.0295 | 0.93 (0.71–1.21) p = 0.29 | 1.46 (0.93–2.30) p = 0.94 | ||||||
1-year | 17.6% | 15% | 19.7% | 12.5% | 23.9% | 14.0% | 40.1% § | 40.0% § | 43.6% § | 53.8% § | |
RESPONSE | ORR | 35.6% | 36.3% | 36.4% | 35.7% | 42.9% | 38.2% | 29.3% | 33.6% | 30.8% | 39.5% |
SD | 27.8% | 34.2% | 26.4% | 32.8% | 23.0% | 34.5% | |||||
PD | 17.1% | 11.9% | 17.4% | 12.3% | 15.1% | 8.2% | |||||
DOR | 6.7 (1.67–39.07) | 4.3 (1.2+–31.5+) | 6.7 (1.6+–39.0+) | 4.5 (1.2–38.7+) | 7.1 (2.1+–39.0+) | 4.2 (1.2+–31.5+) | 5.6 (1.6+–25.6+) | 5.(1.4+–38.7+) | 5.7 (2.6–20.6+) | 4.3 (2.0–31.2+) | |
≥6 mo. | 53.5% | 36.8% | 54.3% | 34.3% | 60.2% | 34.0% | 44.3% | 34.0% | 46.9% | 49.0% |
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Borel, C.; Jung, A.C.; Burgy, M. Immunotherapy Breakthroughs in the Treatment of Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma. Cancers 2020, 12, 2691. https://doi.org/10.3390/cancers12092691
Borel C, Jung AC, Burgy M. Immunotherapy Breakthroughs in the Treatment of Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma. Cancers. 2020; 12(9):2691. https://doi.org/10.3390/cancers12092691
Chicago/Turabian StyleBorel, Christian, Alain C. Jung, and Mickaël Burgy. 2020. "Immunotherapy Breakthroughs in the Treatment of Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma" Cancers 12, no. 9: 2691. https://doi.org/10.3390/cancers12092691