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
- Vermorken, J.B.; Mesia, R.; Rivera, F.; Remenar, E.; Kawecki, A.; Rottey, S.; Erfan, J.; Zabolotnyy, D.; Kienzer, H.-R.; Cupissol, D.; et al. Platinum-Based Chemotherapy plus Cetuximab in Head and Neck Cancer. N. Engl. J. Med. 2008, 359, 1116–1127. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Machiels, J.-P.H.; Haddad, R.I.; Fayette, J.; Licitra, L.F.; Tahara, M.; Vermorken, J.B.; Clement, P.M.; Gauler, T.; Cupissol, D.; Grau, J.J.; et al. Afatinib versus methotrexate as second-line treatment in patients with recurrent or metastatic squamous-cell carcinoma of the head and neck progressing on or after platinum-based therapy (LUX-Head & Neck 1): An open-label, randomised phase 3 trial. Lancet Oncol. 2015, 16, 583–594. [Google Scholar] [PubMed]
- Vermorken, J.B.; Trigo, J.; Hitt, R.; Koralewski, P.; Diaz-Rubio, E.; Rolland, F.; Knecht, R.; Amellal, N.; Schueler, A.; Baselga, J. Open-label, uncontrolled, multicenter phase II study to evaluate the efficacy and toxicity of cetuximab as a single agent in patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck who failed to respond to platinum-based therapy. J. Clin. Oncol. 2007, 25, 2171–2177. [Google Scholar]
- Saloura, V.; Cohen, E.E.W.; Licitra, L.; Billan, S.; Dinis, J.; Lisby, S.; Gauler, T.C. An open-label single-arm, phase II trial of zalutumumab, a human monoclonal anti-EGFR antibody, in patients with platinum-refractory squamous cell carcinoma of the head and neck. Cancer Chemother. Pharmacol. 2014, 73, 1227–1239. [Google Scholar] [CrossRef]
- Ferris, R.L. Immunology and Immunotherapy of Head and Neck Cancer. J Clin Oncol 2015, 33, 3293–3304. [Google Scholar] [CrossRef]
- Seiwert, T.Y.; Burtness, B.; Mehra, R.; Weiss, J.; Berger, R.; Eder, J.P.; Heath, K.; McClanahan, T.; Lunceford, J.; Gause, C.; et al. Safety and clinical activity of pembrolizumab for treatment of recurrent or metastatic squamous cell carcinoma of the head and neck (KEYNOTE-012): An open-label, multicentre, phase 1b trial. Lancet Oncol. 2016, 17, 956–965. [Google Scholar] [CrossRef]
- Chow, L.Q.M.; Haddad, R.; Gupta, S.; Mahipal, A.; Mehra, R.; Tahara, M.; Berger, R.; Eder, J.P.; Burtness, B.; Lee, S.-H.; et al. Antitumor Activity of Pembrolizumab in Biomarker-Unselected Patients With Recurrent and/or Metastatic Head and Neck Squamous Cell Carcinoma: Results From the Phase Ib KEYNOTE-012 Expansion Cohort. J. Clin. Oncol. 2016, 34, 3838–3845. [Google Scholar] [CrossRef]
- Mehra, R.; Seiwert, T.Y.; Gupta, S.; Weiss, J.; Gluck, I.; Eder, J.P.; Burtness, B.; Tahara, M.; Keam, B.; Kang, H.; et al. Efficacy and safety of pembrolizumab in recurrent/metastatic head and neck squamous cell carcinoma: Pooled analyses after long-term follow-up in KEYNOTE-012. Br. J. Cancer 2018, 119, 153–159. [Google Scholar] [CrossRef]
- Bauml, J.; Seiwert, T.Y.; Pfister, D.G.; Worden, F.; Liu, S.V.; Gilbert, J.; Saba, N.F.; Weiss, J.; Wirth, L.; Sukari, A.; et al. Pembrolizumab for Platinum- and Cetuximab-Refractory Head and Neck Cancer: Results From a Single-Arm, Phase II Study. J. Clin. Oncol. 2017, 35, 1542–1549. [Google Scholar] [CrossRef]
- Zandberg, D.P.; Algazi, A.P.; Jimeno, A.; Good, J.S.; Fayette, J.; Bouganim, N.; Ready, N.E.; Clement, P.M.; Even, C.; Jang, R.W.; et al. Durvalumab for recurrent or metastatic head and neck squamous cell carcinoma: Results from a single-arm, phase II study in patients with ≥25% tumour cell PD-L1 expression who have progressed on platinum-based chemotherapy. Eur. J. Cancer 2019, 107, 142–152. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Siu, L.L.; Even, C.; Mesía, R.; Remenar, E.; Daste, A.; Delord, J.-P.; Krauss, J.; Saba, N.F.; Nabell, L.; Ready, N.E.; et al. Safety and Efficacy of Durvalumab With or Without Tremelimumab in Patients With PD-L1–Low/Negative Recurrent or Metastatic HNSCC: The Phase 2 CONDOR Randomized Clinical Trial. JAMA Oncol. 2019, 5, 195–203. [Google Scholar] [CrossRef] [PubMed]
- Brahmer, J.; Reckamp, K.L.; Baas, P.; Crinò, L.; Eberhardt, W.E.E.; Poddubskaya, E.; Antonia, S.; Pluzanski, A.; Vokes, E.E.; Holgado, E.; et al. Nivolumab versus Docetaxel in Advanced Squamous-Cell Non–Small-Cell Lung Cancer. N. Engl. J. Med. 2015, 373, 123–135. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Ferris, R.L.; Blumenschein, G.; Fayette, J.; Guigay, J.; Colevas, A.D.; Licitra, L.; Harrington, K.; Kasper, S.; Vokes, E.E.; Even, C.; et al. Nivolumab for Recurrent Squamous-Cell Carcinoma of the Head and Neck. N. Engl. J. Med. 2016, 375, 1856–1867. [Google Scholar] [CrossRef] [PubMed]
- Segal, N.H.; Ou, S.-H.I.; Balmanoukian, A.S.; Massarelli, E.; Brahmer, J.R.; Weiss, J.; Schoffski, P.; Antonia, S.J.; Massard, C.; Zandberg, D.P.; et al. Updated safety and efficacy of durvalumab (MEDI4736), an anti-PD-L 1 antibody, in patients from a squamous cell carcinoma of the head and neck (SCCHN) expansion cohort. Ann. Oncol. 2016, 27 (Suppl.6), vi328–vi350. [Google Scholar] [CrossRef]
- Ferris, R.L.; Blumenschein, G.; Fayette, J.; Guigay, J.; Colevas, A.D.; Licitra, L.; Harrington, K.J.; Kasper, S.; Vokes, E.E.; Even, C.; et al. Nivolumab vs. investigator’s choice in recurrent or metastatic squamous cell carcinoma of the head and neck: 2-year long-term survival update of CheckMate 141 with analyses by tumor PD-L1 expression. Oral Oncol. 2018, 81, 45–51. [Google Scholar] [CrossRef]
- Cohen, E.E.W.; Soulières, D.; Le Tourneau, C.; Dinis, J.; Licitra, L.; Ahn, M.-J.; Soria, A.; Machiels, J.-P.; Mach, N.; Mehra, R.; et al. Pembrolizumab versus methotrexate, docetaxel, or cetuximab for recurrent or metastatic head-and-neck squamous cell carcinoma (KEYNOTE-040): A randomised, open-label, phase 3 study. Lancet 2019, 393, 156–167. [Google Scholar] [CrossRef]
- Ferris, R.L.; Haddad, R.; Even, C.; Tahara, M.; Dvorkin, M.; Ciuleanu, T.E.; Clement, P.M.; Mesia, R.; Kutukova, S.; Zholudeva, L.; et al. Durvalumab with or without tremelimumab in patients with recurrent or metastatic head and neck squamous cell carcinoma: EAGLE, a randomized, open-label phase III study. Ann. Oncol. 2020, 31, 942–950. [Google Scholar] [CrossRef]
- Haddad, R.; Concha-Benavente, F.; Blumenschein, G.; Fayette, J.; Guigay, J.; Colevas, A.D.; Licitra, L.; Kasper, S.; Vokes, E.E.; Worden, F.; et al. Nivolumab treatment beyond RECIST-defined progression in recurrent or metastatic squamous cell carcinoma of the head and neck in CheckMate 141: A subgroup analysis of a randomized phase 3 clinical trial. Cancer 2019, 125, 3208–3218. [Google Scholar] [CrossRef] [Green Version]
- Even, C.; Daste, A.; Saada-Bouzid, E.; Lefebvre, G.; Fayette, J.; Zanetta, S.; Kaminsky, M.-C.; Cupissol, D.; Prevost, A.; Vauleon, E.; et al. A safety study of nivolumab in patients with recurrent and/or metastatic platinum-refractory squamous cell carcinoma of the head and neck (R/M SCCHN): Interim analysis on 199 patients—The TOPNIVO study on behalf of the GORTEC and the Unicancer Head & Neck Group. J. Clin. Oncol. 2019, 37, 6032. [Google Scholar] [CrossRef]
- Li, W.; Wildsmith, S.; Ye, J.; Si, H.; Morsli, N.; He, P.; Shetty, J.; Yovine, A.J.; Holoweckyj, N.; Raja, R.; et al. Plasma-based tumor mutational burden (bTMB) as predictor for survival in phase III EAGLE study: Durvalumab (D) ± tremelimumab (T) versus chemotherapy (CT) in recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC) after platinum failure. J. Clin. Oncol. 2020, 38, 6511. [Google Scholar] [CrossRef]
- Hanna, G.J.; Lizotte, P.; Cavanaugh, M.; Kuo, F.C.; Shivdasani, P.; Frieden, A.; Chau, N.G.; Schoenfeld, J.D.; Lorch, J.H.; Uppaluri, R.; et al. Frameshift events predict anti–PD-1/L1 response in head and neck cancer. JCI Insight 2018, 3. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Cristescu, R.; Mogg, R.; Ayers, M.; Albright, A.; Murphy, E.; Yearley, J.; Sher, X.; Liu, X.Q.; Lu, H.; Nebozhyn, M.; et al. Pan-tumor genomic biomarkers for PD-1 checkpoint blockade-based immunotherapy. Science 2018, 362, eaar3593. [Google Scholar] [CrossRef] [Green Version]
- Merlano, M.C. The EAGLE study: Two is not always better than one. Ann. Oncol. 2020, 31, 830–831. [Google Scholar] [CrossRef] [PubMed]
- Wang, Q.; Ju, X.; Wang, J.; Fan, Y.; Ren, M.; Zhang, H. Immunogenic cell death in anticancer chemotherapy and its impact on clinical studies. Cancer Lett. 2018, 438, 17–23. [Google Scholar] [CrossRef]
- Economopoulou, P.; Kotsantis, I.; Psyrri, A. The promise of immunotherapy in head and neck squamous cell carcinoma: Combinatorial immunotherapy approaches. ESMO Open 2016, 1, e000122. [Google Scholar] [CrossRef] [PubMed]
- Gandhi, L.; Rodríguez-Abreu, D.; Gadgeel, S.; Esteban, E.; Felip, E.; Angelis, F.D.; Domine, M.; Clingan, P.; Hochmair, M.J.; Powell, S.F.; et al. Pembrolizumab plus Chemotherapy in Metastatic Non–Small-Cell Lung Cancer. N. Engl. J. Med. 2018, 378, 2078–2092. [Google Scholar] [CrossRef]
- Socinski, M.A.; Jotte, R.M.; Cappuzzo, F.; Orlandi, F.; Stroyakovskiy, D.; Nogami, N.; Rodríguez-Abreu, D.; Moro-Sibilot, D.; Thomas, C.A.; Barlesi, F.; et al. Atezolizumab for First-Line Treatment of Metastatic Nonsquamous NSCLC. N. Engl. J. Med. 2018, 378, 2288–2301. [Google Scholar] [CrossRef]
- Horn, L.; Mansfield, A.S.; Szczęsna, A.; Havel, L.; Krzakowski, M.; Hochmair, M.J.; Huemer, F.; Losonczy, G.; Johnson, M.L.; Nishio, M.; et al. First-Line Atezolizumab plus Chemotherapy in Extensive-Stage Small-Cell Lung Cancer. N. Engl. J. Med. 2018, 379, 2220–2229. [Google Scholar] [CrossRef]
- Schmid, P.; Adams, S.; Rugo, H.S.; Schneeweiss, A.; Barrios, C.H.; Iwata, H.; Diéras, V.; Hegg, R.; Im, S.-A.; Shaw Wright, G.; et al. Atezolizumab and Nab-Paclitaxel in Advanced Triple-Negative Breast Cancer. N. Engl. J. Med. 2018, 379, 2108–2121. [Google Scholar] [CrossRef]
- Burtness, B.; Harrington, K.J.; Greil, R.; Soulières, D.; Tahara, M.; de Castro, G.; Psyrri, A.; Baste Rotllan, N.; Neupane, P.C.; Bratland, Å.; et al. KEYNOTE-048: Phase III study of first-line pembrolizumab (P) for recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC). Ann. Oncol. 2018, 29 (Suppl. 8), 729. [Google Scholar] [CrossRef]
- Rischin, D.; Harrington, K.J.; Greil, R.; Soulieres, D.; Tahara, M.; de Castro, G.; Psyrri, A.; Baste, N.; Neupane, P.C.; Bratland, A.; et al. Protocol-specified final analysis of the phase 3 KEYNOTE-048 trial of pembrolizumab (pembro) as first-line therapy for recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC). J. Clin. Oncol. 2019, 37 (Suppl.15), 6000. [Google Scholar] [CrossRef]
- Burtness, B.; Harrington, K.J.; Greil, R.; Soulières, D.; Tahara, M.; de Castro, G.; Psyrri, A.; Basté, N.; Neupane, P.; Bratland, Å.; et al. Pembrolizumab alone or with chemotherapy versus cetuximab with chemotherapy for recurrent or metastatic squamous cell carcinoma of the head and neck (KEYNOTE-048): A randomised, open-label, phase 3 study. The Lancet 2019, 394, 1915–1928. [Google Scholar] [CrossRef]
- European Medicines Agency: Committee for Medicinal Products for Human Use (CHMP). Public Assessment Report, Keytruda, October 2019. Available online: https://www.ema.europa.eu/en/documents/variation-report/keytruda-h-c-3820-ii-0065-epar-assessment-report-variation_en.pdf (accessed on 23 August 2020).
- Borcoman, E.; Kanjanapan, Y.; Champiat, S.; Kato, S.; Servois, V.; Kurzrock, R.; Goel, S.; Bedard, P.; Le Tourneau, C. Novel patterns of response under immunotherapy. Ann. Oncol. 2019, 30, 385–396. [Google Scholar] [CrossRef] [PubMed]
- Saâda-Bouzid, E.; Defaucheux, C.; Karabajakian, A.; Coloma, V.P.; Servois, V.; Paoletti, X.; Even, C.; Fayette, J.; Guigay, J.; Loirat, D.; et al. Hyperprogression during anti-PD-1/PD-L1 therapy in patients with recurrent and/or metastatic head and neck squamous cell carcinoma. Ann. Oncol. 2017, 28, 1605–1611. [Google Scholar] [CrossRef]
- Harrington, K.J.; Rischin, D.; Greil, R.; Soulieres, D.; Tahara, M.; Castro, G.; Psyrri, A.; Baste, N.; Neupane, P.C.; Bratland, Å.; et al. KEYNOTE-048: Progression after the next line of therapy following pembrolizumab (P) or P plus chemotherapy (P + C) vs. EXTREME (E) as first-line (1L) therapy for recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC). J. Clin. Oncol. 2020, 38 (Suppl.15), 6505. [Google Scholar] [CrossRef]
- Guigay, J.; Fayette, J.; Mesia, R.; Saada-Bouzid, E.; Lafond, C.; Geoffrois, L.; Martin, L.; Capitain, O.; Cupissol, D.; Castanie, H.; et al. TPExtreme randomized trial: Quality of Life (QoL) and survival according to second-line treatments in patients with recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC). J. Clin. Oncol. 2020, 38 (Suppl.15), 6507. [Google Scholar] [CrossRef]
- Saleh, K.; Daste, A.; Martin, N.; Pons-Tostivint, E.; Auperin, A.; Herrera-Gomez, R.G.; Baste-Rotllan, N.; Bidault, F.; Guigay, J.; Le Tourneau, C.; et al. Response to salvage chemotherapy after progression on immune checkpoint inhibitors in patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck. Eur. J. Cancer 2019, 121, 123–129. [Google Scholar] [CrossRef]
- Rotte, A. Combination of CTLA-4 and PD-1 blockers for treatment of cancer. J. Exp. Clin. Cancer Res. 2019, 38, 255. [Google Scholar] [CrossRef]
- Antonia, S.; Goldberg, S.B.; Balmanoukian, A.; Chaft, J.E.; Sanborn, R.E.; Gupta, A.; Narwal, R.; Steele, K.; Gu, Y.; Karakunnel, J.J.; et al. Safety and antitumour activity of durvalumab plus tremelimumab in non-small cell lung cancer: A multicentre, phase 1b study. Lancet Oncol. 2016, 17, 299–308. [Google Scholar] [CrossRef] [Green Version]
- Motzer, R.J.; Tannir, N.M.; McDermott, D.F.; Arén Frontera, O.; Melichar, B.; Choueiri, T.K.; Plimack, E.R.; Barthélémy, P.; Porta, C.; George, S.; et al. Nivolumab plus Ipilimumab versus Sunitinib in Advanced Renal-Cell Carcinoma. N. Engl. J. Med. 2018, 378, 1277–1290. [Google Scholar] [CrossRef]
- Wolchok, J.D.; Kluger, H.; Callahan, M.K.; Postow, M.A.; Rizvi, N.A.; Lesokhin, A.M.; Segal, N.H.; Ariyan, C.E.; Gordon, R.-A.; Reed, K.; et al. Nivolumab plus ipilimumab in advanced melanoma. N. Engl. J. Med. 2013, 369, 122–133. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Study of Nivolumab in Combination With Ipilimumab Versus Nivolumab in Combination With Ipilimumab Placebo in Patients With Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck (CheckMate 714). Available online: https://clinicaltrials.gov/ct2/show/NCT02823574 (accessed on 23 August 2020).
- Hutloff, A.; Dittrich, A.M.; Beier, K.C.; Eljaschewitsch, B.; Kraft, R.; Anagnostopoulos, I.; Kroczek, R.A. ICOS is an inducible T-cell co-stimulator structurally and functionally related to CD28. Nature 1999, 397, 263–266. [Google Scholar] [CrossRef] [PubMed]
- Mayes, P.A.; Hance, K.W.; Hoos, A. The promise and challenges of immune agonist antibody development in cancer. Nat. Rev. Drug Discov. 2018, 17, 509–527. [Google Scholar] [CrossRef] [PubMed]
- Brett, S.; Yadavilli, S.; Seestaller-Wehr, L.; Bhattacharya, S.; Jackson, H.; Bi, M.; Willoughby, J.; Zhang, T.; Liu, Y.-B.; Katlinskaya, Y.K.; et al. Preclinical evaluation of a non-depleting, first-in-class humanized IgG4 agonist anti-ICOS antibody. Ann. Oncol. 2018, 29 (Suppl. 8), viii652–viii653. [Google Scholar] [CrossRef]
- Yadavilli, S.; Zhang, T.; Hahn, A.; Seestaller-Wehr, L.M.; Shi, H.; Liu, Y.-B.; de Young, M.P.; Kilian, D.J.; Bi, M.; Adam, M.P.; et al. Abstract 1637: ICOS agonism induces potent immune activation and anti-tumor response in non-clinical models. Cancer Res. 2017, 77, 1637. [Google Scholar]
- Rischin, D.; Groenland, S.L.; Lim, A.M.L.; Martin-Liberal, J.; Moreno, V.; Perez, J.M.T.; Tourneau, C.L.; Mathew, M.; Cho, D.C.; Hansen, A.R.; et al. Inducible T cell costimulatory (ICOS) receptor agonist, GSK3359609 (GSK609) alone and in combination with pembrolizumab (pembro): Preliminary results from INDUCE-1 expansion cohorts (EC) in head and neck squamous cell carcinoma (HNSCC). Ann. Oncol. 2019, 30, v454–v455. [Google Scholar] [CrossRef]
- Angevin, E.; Groenland, S.L.; Lim, A.M.L.; Martin-Liberal, J.; Moreno, V.; Trigo, J.M.; Le Tourneau, C.; Mathew, M.; Cho, D.C.; Hansen, A.R.; et al. Updated analysis of the inducible T-cell co-stimulatory receptor (ICOS) agonist, GSK3359609 (GSK609), combination with pembrolizumab (PE) in patients (pts) with anti-PD-1/L1 treatment-naïve head and neck squamous cell carcinoma (HNSCC). J. Clin. Oncol. 2020, 38 (Suppl. 15), 6517. [Google Scholar] [CrossRef]
- Cohen, R.B.; Bauman, J.R.; Salas, S.; Colevas, A.D.; Even, C.; Cupissol, D.; Posner, M.R.; Lefebvre, G.; Saada-Bouzid, E. Maureen Bernadach, Seiwert, T. Y. (2020). Combination of monalizumab and cetuximab in recurrent or metastatic head and neck cancer patients previously treated with platinum-based chemotherapy and PD-(L) 1 inhibitors. J. Clin. Oncol. 2020, 38, 6516. [Google Scholar] [CrossRef]
- Taylor, M.H.; Lee, C.-H.; Makker, V.; Rasco, D.; Dutcus, C.E.; Wu, J.; Stepan, D.E.; Shumaker, R.C.; Motzer, R.J. Phase IB/II Trial of Lenvatinib Plus Pembrolizumab in Patients With Advanced Renal Cell Carcinoma, Endometrial Cancer, and Other Selected Advanced Solid Tumors. J. Clin. Oncol. 2020, 38, 1154–1163. [Google Scholar] [CrossRef]
- Van Hall, T.; André, P.; Horowitz, A.; Ruan, D.F.; Borst, L.; Zerbib, R.; Narni-Mancinelli, E.; van der Burg, S.H.; Vivier, E. Monalizumab: Inhibiting the novel immune checkpoint NKG2A. J. Immunother. Cancer 2019, 7, 263. [Google Scholar] [CrossRef]
- Galot, R.; Tourneau, C.L.; Saada-Bouzid, E.; Daste, A.; Even, C.; Debruyne, P.R.; Henry, S.; Zanetta, S.; Rutten, A.; Licitra, L.F.; et al. A phase II study of monalizumab in patients with recurrent/metastatic (RM) squamous cell carcinoma of the head and neck (SCCHN): Results of the I1 cohort of the EORTC-HNCG-1559 trial (UPSTREAM). Ann. Oncol. 2019, 30, v449–v450. [Google Scholar] [CrossRef]
- André, P.; Denis, C.; Soulas, C.; Bourbon-Caillet, C.; Lopez, J.; Arnoux, T.; Bléry, M.; Bonnafous, C.; Gauthier, L.; Morel, A.; et al. Anti-NKG2A mAb Is a Checkpoint Inhibitor that Promotes Anti-tumor Immunity by Unleashing Both T and NK Cells. Cell 2018, 175, 1731–1743.e13. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Cohen, R.B.; Lefebvre, G.; Posner, M.R.; Bauman, J.R.; Salas, S.; Even, C.; Saada-Bouzid, E.; Seiwert, T.; Colevas, D.; Calmels, F.; et al. 1134P-Monalizumab in combination with cetuximab in patients (pts) with recurrent or metastatic (R/M) head and neck cancer (SCCHN) previously treated or not with PD-(L)1 inhibitors (IO): 1-year survival data. Ann. Oncol. 2019, 30 (Suppl. 5), v460. [Google Scholar] [CrossRef]
- Ott, P.A.; Hodi, F.S.; Buchbinder, E.I. Inhibition of Immune Checkpoints and Vascular Endothelial Growth Factor as Combination Therapy for Metastatic Melanoma: An Overview of Rationale, Preclinical Evidence, and Initial Clinical Data. Front. Oncol. 2015, 5, 202. [Google Scholar] [CrossRef] [Green Version]
- Kato, Y.; Bao, X.; Macgrath, S.; Tabata, K.; Hori, Y.; Tachino, S.; Matijevici, M.; Funahashi, Y.; Matsui, J. 2PD-Lenvatinib mesilate (LEN) enhanced antitumor activity of a PD-1 blockade agent by potentiating Th1 immune response. Ann. Oncol. 2016, 27, vi1. [Google Scholar] [CrossRef]
- Siu, L.L.; Burtness, B.; Cohen, E.E.W.; Harrington, K.J.; Licitra, L.F.; Rischin, D.; Zhu, Y.; Lee, C.P.; Pinheiro, C.; Swaby, R.F.; et al. Phase III LEAP-010 study: First-line pembrolizumab with or without lenvatinib in recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC). J. Clin. Oncol. 2020. [Google Scholar] [CrossRef]
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% |
© 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
Share and Cite
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
APA StyleBorel, C., Jung, A. C., & Burgy, M. (2020). Immunotherapy Breakthroughs in the Treatment of Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma. Cancers, 12(9), 2691. https://doi.org/10.3390/cancers12092691