Get 20M+ Full-Text Papers For Less Than $1.50/day. Start a 14-Day Trial for You or Your Team.

Learn More →

ASCO 2021 highlights head and neck cancer: nasopharyngeal carcinoma

ASCO 2021 highlights head and neck cancer: nasopharyngeal carcinoma short review memo (2021) 14:331–334 https://doi.org/10.1007/s12254-021-00758-6 ASCO 2021 highlights head and neck cancer: nasopharyn- geal carcinoma Thorsten Fuereder Received: 16 August 2021 / Accepted: 11 September 2021 / Published online: 27 October 2021 © The Author(s) 2021 Summary During the ASCO 2021 virtual meeting, Metastatic NPC multiple clinically relevant studies were presented addressing open questions regarding the therapy of JUPITER-02 trial: immunotherapy with toripalimab nasopharyngeal carcinomas (NPC): Is immunother- plus chemotherapy vs. chemotherapy alone [1] apy plus chemotherapy the new first line standard of care for patients in the recurrent/metastatic setting? This multicenter randomized double-blind placebo Is adjuvant therapy with capecitabine in high risk controlled phase III study presented at the plenary NPC patients post chemoradiation (CRT) beneficial? session included 289 patients suffering from treat- Is there a role for treatment intensification by adju- ment naïve recurrent/metastatic (R/M) NPC. Patients vant metronomic capecitabine in NPC patients post were randomized to a standard of care (SoC) arm induction chemotherapy and CRT? This article sum- (143 patients) receiving chemotherapy with cisplatin/ marizes the most significant NPC studies presented gemcitabine (GP) plus placebo and to an experimen- at the ASCO 2021 virtual meeting and discusses the tal group (146 patients) receiving GP plus toripalimab, data in the context of the current literature. a humanized programmed death receptor-1 (PD-1) monoclonal antibody. Chemotherapy was given for Keywords Nasopharyngeal carcinoma · up to six cycles followed by placebo or toripalimab Immunotherapy · Adjuvant therapy · Toripalimab · maintenance. Baseline characteristics were well bal- Camrelizumab · Capecitabine anced between the arms. Of note, the majority of patients (99%) suffered from World Health Organiza- tion (WHO) type II/III NPC and were PD-L1 positive Introduction (75%). The primary endpoint was progression-free During the virtual American Society of Clinical Oncol- survival (PFS) and was met. The PFS in the GP+ tori- ogy (ASCO) 2021, scientific meeting several interest- palimab arm was 11.7 months vs. 8.0 months in the ing studies in the field of head and neck cancer were SoC group (HR: 0.52; 95% CI: 0.36–0.74; p = 0.0003). reported. In particular clinical trials conducted in lo- The benefit was seen across all subgroups includ- cally advanced and metastatic nasopharyngeal carci- ing PD-L1-negative patients (hazard ratio [HR] 0.35; noma (NPC) investigating either novel strategies in the 95% confidence interval [CI] 0.15–0.81) or patients adjuvant setting or novel compounds in stage IVB dis- with an Epstein–Barr virus (EBV) copy number above ease might be potentially practice changing in the fu- 2000 (HR 0.46; 95% CI 0.3–0.72). Overall survival ture and are reviewed in this manuscript. (OS) data are not mature yet and no statistically sig- nificant difference between the treatment arms was observed (HR 0.603; 95% CI 0.364–0.997; p = 0.0462). Apart from that, both duration of response (DoR) and overall response rate (ORR) was longer/higher in the T. Fuereder, MD () experimental arm (DoR: 10.0 vs. 5.7 months; ORR Department of Medicine I & Comprehensive Cancer Center, 77.4% vs. 66.4%). The side effect profile was well Division of Clinical Oncology, Medical University of Vienna, manageable and no new safety issues were reported. Währinger Gürtel 18–20, 1090 Vienna, Austria thorsten.fuereder@meduniwien.ac.at K ASCO 2021 highlights head and neck cancer: nasopharyngeal carcinoma 331 short review IVA NPC patients (excluding T3-4 N0 and T3N1) were CAPTAIN-1st trial: immunotherapy with eligible to receive metronomic capecitabine vs. ob- camrelizumab plus chemotherapy vs. chemotherapy servation. Primary endpoint was failure-free survival alone [2] (FFS) at 3 years. Secondary endpoints included OS, The multicenter randomized double-blind placebo- distant FFS and locoregional FFS. Prior induction controlled Chinese CAPTAIN-1st III study aimed at chemotherapy (IC) was allowed. In total 406 patients demonstrating the superiority of GP plus the PD-1 were randomized (204 and 202 per arm) and the inhibitor camrelizumab over GP plus placebo in un- majority was exposed to IC (77%). The study was treated R/M NPC. The study design, maintenance positive and reached all endpoints, since metronomic therapy and endpoints were similar to the afore- capecitabine improved FFS (85.3% vs. 75.7%; HR 0.5; mentioned JUPITER-02 study. In total, 263 patients 95% CI 0.32–0.79; p = 0.002), OS (93.3% vs. 88.6%; (SoC: 129 patients; camrelizumab/GP: 134 patients) HR 0.44; 95% CI 0.22–0.88; p = 0.018), distant FFS were randomized. The median PFS in the camre- (89.4% vs. 82.1%) and locoregional FFS (92.6% vs. lizumab plusGPgroup was10.8 monthsand superior 87.8%) compared to observation. A benefit across all to the PFS in the GP arm (6.9 months; HR 0.51; 95% subgroups was observed. The toxicity profile was ben- CI 0.37–0.69; p < 0.0001). Likewise, the PFS benefit eficial and hand–foot syndrome the most common was observed across all subgroups. In contrast to the adverse event (58%). JUPITER-02 study, the PD-L1 status of the study popu- lation was not reported. Addition of camrelizumab to Standard dose capecitabine as adjuvant therapy [5] SoC did not result in a statistically significant OS ben- efit yet and a longer follow-up time is needed to draw In contrast to the study outlined above, eight cycles a final conclusion (OS not reached vs. 22.6 months of standard dose (1000 mg/m bid) capecitabine were for the SoC group; HR 0.67; 95% CI 0.41–1.11). GP administered in the experimental arm of a similar ran- plus camrelizumab resulted in a higher ORR (88.1%) domizedcontrolledphase III in high-risk locally ad- compared to GP (80.6%). DoR was longer in the ex- vanced NPC patients treated with curative intent. Be- perimental arm than in the SoC arm (9.9 months vs. sides tumor stage, additional risk factors such as EBV 5.7 months; HR 0.48; 95% CI 0.34–0.68; p < 0.0001). DNA > 20,000 copies/ml, high tumor volume, multiple Toxicity was similar to what was reported in previ- neck node metastases or a maximum standard up- ous camrelizumab plus chemotherapy studies. The take value > 10 as measured by PET-CT was required high rate (up to 60%) of grade I/II reactive capillary for eligibility. Patients exposed to prior IC were ex- hemangiomas (RCEPs), which is well described for cluded. FFS at 3 years was the primary endpoint. In camrelizumab therapy, is worth mentioning despite all, 180 patients (90 per arm) were randomized. FFS being well manageable. was superior in the capecitabine arm compared to the observation group (87.7% vs. 73.3%; HR 0.52; 95% CI 0.29–0.97; p = 0.037). However, secondary endpoints Maintenance capecitabine plus best supportive care such as OS, locoregional recurrence-free survival or versus best supportive care [3] distant-metastasis-free survival were not met or are A single center open label randomized phase III study immature. evaluated the role of capecitabine (1250 mg/m bid) maintenance therapy administered after 4–6 cycles in- Discussion duction chemotherapy (cisplatin/paclitaxel) vs. best supportive care in newly diagnosed R/M NPC pa- NPC is endemic in southern China and Hong Kong tients. A total of 140 patients were randomized. The with an incidence of approximately 25 cases per primary endpoint was PFS and was met. The PFS 100,000, while it is regarded as an orphan disease in in the capecitabine arm was superior to the SoC the western world [6–8]. In the endemic regions NPC group (35.2 months vs. 9.1 months; HR 0.426; 95% CI is mainly associated with EBV infection, whereas in 0.248–0.731; p = 0.0001). Toxicity was well manageable the USA and Europe alcohol and tobacco use com- in the capecitabine group. prise the major risk factors for NPC development [9, 10]. From this background, it seems obvious why no large randomized phase III studies have been Locally advanced NPC performed outside endemic areas. The current NPC treatment guidelines are mainly based on the evi- Metronomic capecitabine as adjuvant therapy [4] dence generated by clinical trials conducted in Asia The efficacy and safety of metronomic capecitabine resulting in underrepresentation of WHO type I NPC 650 mg/m bid given for up to 1 year vs. obser- patients. vation in patients with locally advanced high-risk In the R/M setting GP is the SoC first-line approach NPC treated with curative chemoradiation was in- irrespective of the subtype resulting in a median PFS vestigated in a randomized controlled phase III trial and OS of 7 and 29 months, respectively [11]. Since presented during the oral abstract session. Stage III- NPC is regarded as an immunogenic malignancy char- 332 ASCO 2021 highlights head and neck cancer: nasopharyngeal carcinoma K short review acterized by high rates of tumor-infiltrating lympho- Funding Open access funding provided by Medical University cytes, multiple single arm phase II studies evaluated of Vienna. the efficacy of immune checkpoint inhibitors such as Conflict of interest T. Fuereder is member of advisory boards pembrolizumab, nivolumab or toripalimab in the sec- and/or received honoraria from MSD, MERCK, Roche, No- ond-line R/M setting [12–16]. Based on the promising vartis, Amgen, Pfizer, BMS and Boehringer Ingelheim, and outcomes of these studies it is not surprising that at- received research funding from MSD and MERCK. tempts have been made to transfer immunotherapy Open Access This article is licensed under a Creative Com- to earlier lines and combine it with chemotherapy. mons Attribution 4.0 International License, which permits Although Jupiter-02 and Captain-1st clearly support use, sharing, adaptation, distribution and reproduction in this approach, a couple of open questions and lim- any medium or format, as long as you give appropriate credit itations remain: (1) The PFS curves overlap during to the original author(s) and the source, provide a link to concurrent immunotherapyplus chemotherapyphase the Creative Commons licence, and indicate if changes were and separate during maintenance therapy. This find- made. The images or other third party material in this article ing suggests that an active comparator such as gem- are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material citabine would have been important in the control is not included in the article’s Creative Commons licence and group. (2) OS data are immature and it is unclear your intended use is not permitted by statutory regulation or whether immunotherapy plus chemotherapy resulted exceeds the permitted use, you will need to obtain permis- in an OS benefit in R/M NPC patients compared to sion directly from the copyright holder. To view a copy of this SoC. (3) Neither toripalimab nor camrelizumab are licence, visit http://creativecommons.org/licenses/by/4.0/. approved outside of Asia and substitution of those agents by any available checkpoint inhibitor does not seem to be justified. References Therefore, the combination of immunotherapy 1. Xu R-H, Mai H-Q, Chen Q-Y, et al. JUPITER-02: Random- with chemotherapy in untreated R/M NPC remains ized,double-blind,phaseIIIstudyoftoripalimaborplacebo investigational until a more widespread regulatory plus gemcitabine and cisplatin as first-line treatment for re- approval and additional follow-up is available. current or metastatic nasopharyngeal carcinoma (NPC). As for high-risk locally advanced NPC, the SoC ap- J Clin Oncol. 2021;39:LBA2. proach (IC followed by chemoradiation [CRT] or CRT 2. Zhang L, Yang Y, Qu S, et al. Camrelizumab versus placebo followed by adjuvant chemotherapy) results in a 3- combined with gemcitabine and cisplatin for recurrent year FFS of approximately 80% [17–19]. Especially the or metastatic nasopharyngeal carcinoma: a randomized, double-blind, phase3 trial. J Clin Oncol. 2021;39:6000. role of adjuvant chemotherapy in patients who did not 3. LiuG-Y,LiW-Z,WangD-S,etal. Capecitabinemaintenance undergo IC is still a matter of debate and associated therapy after induction chemotherapy in newly diagnosed with considerable toxicity. metastatic nasopharyngeal carcinoma: an open-label, ran- Both capecitabine trials presented promising data. domized,controlled,phasetrial. JClinOncol. 2021;39:6044. However, it is surprising that the FFS in the metro- 4. Ma J, Chen Y-P, Sun Y, et al. Metronomic capecitabine as ad- nomic and standard dose capecitabine studies out- juvant therapy in locoregionally advanced nasopharyngeal lined above are comparable despite more intensive carcinoma: a phase 3, multicenter, randomized controlled trial. J Clin Oncol. 2021;39:6003. treatment with IC in the metronomic capecitabine 5. Miao J, Wang L, Tan SH, et al. Adjuvant capecitabine study. To identify patients who derive a benefit from in locoregionally advanced nasopharyngeal carcinoma: a adjuvant capecitabine, use of a predictive biomarker multicenter randomized controlled phase III trial. J Clin is highly desirable. Since a recent study investigating Oncol. 2021;39:6005. the role of postradiation EBV DNA as a biomarker 6. Chang ET, Adami HO. The enigmatic epidemiology of for adjuvant chemotherapy did not show a difference nasopharyngeal carcinoma. Cancer Epidemiol Biomarkers Prev. 2006;15:1765–77. with respect to relapse-free survival, further research 7. Lee AW, Foo W, Mang O, et al. Changing epidemiology is needed and the use of EBV DNA to select patients of nasopharyngeal carcinoma in Hong Kong over a 20- for adjuvant therapy is not recommended outside year period (1980–99): an encouraging reduction in both clinical trials [20]. incidenceandmortality. IntJ Cancer. 2003;103:680–5. 8. Ono T, Azuma K, Kawahara A, et al. Prognostic stratification ofpatientswithnasopharyngealcarcinomabasedontumor Conclusion immunemicroenvironment. HeadNeck. 2018;40:2007–19. 9. Chua MLK, Wee JTS, Hui EP, Chan ATC. Nasopharyngeal Despite its chemo- and radiotherapy-sensitive tumor carcinoma. Lancet. 2016;387:1012–24. biology, the treatment of NPC remains a clinical chal- 10. Vaughan TL, Shapiro JA, Burt RD, et al. Nasopharyngeal lenge. The outcomes in the R/M setting are poor and cancer in a low-risk population: defining risk factors by adjuvant therapy after CRT is not tolerated by the ma- histological type. Cancer Epidemiol Biomarkers Prev. jority of the patients. Therefore, the immunotherapy 1996;5:587–93. and adjuvant capecitabine phase III NPC studies pre- 11. Zhang L, Huang Y, Hong S, et al. Gemcitabine plus cisplatin versus fluorouracil plus cisplatin in recurrent or metastatic sented during the virtual ASCO 2021 conference will nasopharyngeal carcinoma: a multicentre, randomised, potentially change clinical practice depending on the open-label, phase3 trial. Lancet. 2016;388:1883–92. outcomes of longer follow-up. K ASCO 2021 highlights head and neck cancer: nasopharyngeal carcinoma 333 short review 12. Khanna R, Busson P, Burrows SR, et al. Molecular character- 18. Zhang Y, Chen L, Hu GQ, et al. Gemcitabine and cisplatin ization of antigen-processing function in nasopharyngeal induction chemotherapy in nasopharyngeal carcinoma. carcinoma (NPC): evidence for efficient presentation of NEngl J Med. 2019;381:1124–35. Epstein-Barr virus cytotoxic T-cell epitopes by NPC cells. 19. Blanchard P, Lee A, Marguet S, et al. Chemotherapy and ra- Cancer Res. 1998;58:310–4. diotherapy in nasopharyngeal carcinoma: an update of the 13. Pai S, O’Sullivan B, Abdul-Jabbar I, et al. Nasopharyngeal MAC-NPCmeta-analysis. LancetOncol. 2015;16:645–55. carcinoma-associated Epstein-Barr virus-encoded onco- 20. Chan ATC, Hui EP, Ngan RKC, et al. Analysis of plasma gene latent membrane protein 1 potentiates regulatory Epstein-Barr virus DNA in nasopharyngeal cancer after T-cell function. Immunol Cell Biol. 2007;85:370–7. chemoradiation to identify high-risk patients for adjuvant 14. Hsu C, Lee SH, Ejadi S, et al. Safety and antitumor activity chemotherapy: a randomized controlled trial. J Clin Oncol. of pembrolizumab in patients with programmed death- 2018; https://doi.org/10.1200/JCO.2018.77.7847. ligand 1-positive nasopharyngeal carcinoma: results of the Publisher’s Note Springer Nature remains neutral with regard KEYNOTE-028 study. J Clin Oncol. 2017;35(36):4050–6. to jurisdictional claims in published maps and institutional 15. Ma BBY, Lim WT, Goh BC, et al. Antitumor activity of affiliations. nivolumab in recurrent and metastatic nasopharyngeal carcinoma: an international, multicenter study of the mayo clinic phase 2 consortium (NCI-9742). J Clin Oncol. 2018;36:1412–8. 16. Wang FH,Wei XL,Feng J,et al. Efficacy, safety, and 7 For latest news from interna- correlative biomarkers of toripalimab in previously treated tional oncology congresses see: recurrentormetastaticnasopharyngealcarcinoma: aphase http://www.springermedizin.at/ II clinical trial (POLARIS-02). J Clin Oncol. 2021;39:704–12. memo-inoncology 17. Sun Y,Li WF, Chen NY,et al. Induction chemother- apy plus concurrent chemoradiotherapy versus concur- rent chemoradiotherapy alone in locoregionally advanced nasopharyngeal carcinoma: a phase 3, multicentre, ran- domisedcontrolledtrial. LancetOncol. 2016;17:1509–20. 334 ASCO 2021 highlights head and neck cancer: nasopharyngeal carcinoma K http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png memo - Magazine of European Medical Oncology Springer Journals

ASCO 2021 highlights head and neck cancer: nasopharyngeal carcinoma

Download PDF
4 pages

Loading next page...
 
/lp/springer-journals/asco-2021-highlights-head-and-neck-cancer-nasopharyngeal-carcinoma-W0h9XzdF7h

References (30)

Publisher
Springer Journals
Copyright
2021 The Author(s)
ISSN
1865-5041
eISSN
1865-5076
DOI
10.1007/s12254-021-00758-6
Publisher site
See Article on Publisher Site

Abstract

short review memo (2021) 14:331–334 https://doi.org/10.1007/s12254-021-00758-6 ASCO 2021 highlights head and neck cancer: nasopharyn- geal carcinoma Thorsten Fuereder Received: 16 August 2021 / Accepted: 11 September 2021 / Published online: 27 October 2021 © The Author(s) 2021 Summary During the ASCO 2021 virtual meeting, Metastatic NPC multiple clinically relevant studies were presented addressing open questions regarding the therapy of JUPITER-02 trial: immunotherapy with toripalimab nasopharyngeal carcinomas (NPC): Is immunother- plus chemotherapy vs. chemotherapy alone [1] apy plus chemotherapy the new first line standard of care for patients in the recurrent/metastatic setting? This multicenter randomized double-blind placebo Is adjuvant therapy with capecitabine in high risk controlled phase III study presented at the plenary NPC patients post chemoradiation (CRT) beneficial? session included 289 patients suffering from treat- Is there a role for treatment intensification by adju- ment naïve recurrent/metastatic (R/M) NPC. Patients vant metronomic capecitabine in NPC patients post were randomized to a standard of care (SoC) arm induction chemotherapy and CRT? This article sum- (143 patients) receiving chemotherapy with cisplatin/ marizes the most significant NPC studies presented gemcitabine (GP) plus placebo and to an experimen- at the ASCO 2021 virtual meeting and discusses the tal group (146 patients) receiving GP plus toripalimab, data in the context of the current literature. a humanized programmed death receptor-1 (PD-1) monoclonal antibody. Chemotherapy was given for Keywords Nasopharyngeal carcinoma · up to six cycles followed by placebo or toripalimab Immunotherapy · Adjuvant therapy · Toripalimab · maintenance. Baseline characteristics were well bal- Camrelizumab · Capecitabine anced between the arms. Of note, the majority of patients (99%) suffered from World Health Organiza- tion (WHO) type II/III NPC and were PD-L1 positive Introduction (75%). The primary endpoint was progression-free During the virtual American Society of Clinical Oncol- survival (PFS) and was met. The PFS in the GP+ tori- ogy (ASCO) 2021, scientific meeting several interest- palimab arm was 11.7 months vs. 8.0 months in the ing studies in the field of head and neck cancer were SoC group (HR: 0.52; 95% CI: 0.36–0.74; p = 0.0003). reported. In particular clinical trials conducted in lo- The benefit was seen across all subgroups includ- cally advanced and metastatic nasopharyngeal carci- ing PD-L1-negative patients (hazard ratio [HR] 0.35; noma (NPC) investigating either novel strategies in the 95% confidence interval [CI] 0.15–0.81) or patients adjuvant setting or novel compounds in stage IVB dis- with an Epstein–Barr virus (EBV) copy number above ease might be potentially practice changing in the fu- 2000 (HR 0.46; 95% CI 0.3–0.72). Overall survival ture and are reviewed in this manuscript. (OS) data are not mature yet and no statistically sig- nificant difference between the treatment arms was observed (HR 0.603; 95% CI 0.364–0.997; p = 0.0462). Apart from that, both duration of response (DoR) and overall response rate (ORR) was longer/higher in the T. Fuereder, MD () experimental arm (DoR: 10.0 vs. 5.7 months; ORR Department of Medicine I & Comprehensive Cancer Center, 77.4% vs. 66.4%). The side effect profile was well Division of Clinical Oncology, Medical University of Vienna, manageable and no new safety issues were reported. Währinger Gürtel 18–20, 1090 Vienna, Austria thorsten.fuereder@meduniwien.ac.at K ASCO 2021 highlights head and neck cancer: nasopharyngeal carcinoma 331 short review IVA NPC patients (excluding T3-4 N0 and T3N1) were CAPTAIN-1st trial: immunotherapy with eligible to receive metronomic capecitabine vs. ob- camrelizumab plus chemotherapy vs. chemotherapy servation. Primary endpoint was failure-free survival alone [2] (FFS) at 3 years. Secondary endpoints included OS, The multicenter randomized double-blind placebo- distant FFS and locoregional FFS. Prior induction controlled Chinese CAPTAIN-1st III study aimed at chemotherapy (IC) was allowed. In total 406 patients demonstrating the superiority of GP plus the PD-1 were randomized (204 and 202 per arm) and the inhibitor camrelizumab over GP plus placebo in un- majority was exposed to IC (77%). The study was treated R/M NPC. The study design, maintenance positive and reached all endpoints, since metronomic therapy and endpoints were similar to the afore- capecitabine improved FFS (85.3% vs. 75.7%; HR 0.5; mentioned JUPITER-02 study. In total, 263 patients 95% CI 0.32–0.79; p = 0.002), OS (93.3% vs. 88.6%; (SoC: 129 patients; camrelizumab/GP: 134 patients) HR 0.44; 95% CI 0.22–0.88; p = 0.018), distant FFS were randomized. The median PFS in the camre- (89.4% vs. 82.1%) and locoregional FFS (92.6% vs. lizumab plusGPgroup was10.8 monthsand superior 87.8%) compared to observation. A benefit across all to the PFS in the GP arm (6.9 months; HR 0.51; 95% subgroups was observed. The toxicity profile was ben- CI 0.37–0.69; p < 0.0001). Likewise, the PFS benefit eficial and hand–foot syndrome the most common was observed across all subgroups. In contrast to the adverse event (58%). JUPITER-02 study, the PD-L1 status of the study popu- lation was not reported. Addition of camrelizumab to Standard dose capecitabine as adjuvant therapy [5] SoC did not result in a statistically significant OS ben- efit yet and a longer follow-up time is needed to draw In contrast to the study outlined above, eight cycles a final conclusion (OS not reached vs. 22.6 months of standard dose (1000 mg/m bid) capecitabine were for the SoC group; HR 0.67; 95% CI 0.41–1.11). GP administered in the experimental arm of a similar ran- plus camrelizumab resulted in a higher ORR (88.1%) domizedcontrolledphase III in high-risk locally ad- compared to GP (80.6%). DoR was longer in the ex- vanced NPC patients treated with curative intent. Be- perimental arm than in the SoC arm (9.9 months vs. sides tumor stage, additional risk factors such as EBV 5.7 months; HR 0.48; 95% CI 0.34–0.68; p < 0.0001). DNA > 20,000 copies/ml, high tumor volume, multiple Toxicity was similar to what was reported in previ- neck node metastases or a maximum standard up- ous camrelizumab plus chemotherapy studies. The take value > 10 as measured by PET-CT was required high rate (up to 60%) of grade I/II reactive capillary for eligibility. Patients exposed to prior IC were ex- hemangiomas (RCEPs), which is well described for cluded. FFS at 3 years was the primary endpoint. In camrelizumab therapy, is worth mentioning despite all, 180 patients (90 per arm) were randomized. FFS being well manageable. was superior in the capecitabine arm compared to the observation group (87.7% vs. 73.3%; HR 0.52; 95% CI 0.29–0.97; p = 0.037). However, secondary endpoints Maintenance capecitabine plus best supportive care such as OS, locoregional recurrence-free survival or versus best supportive care [3] distant-metastasis-free survival were not met or are A single center open label randomized phase III study immature. evaluated the role of capecitabine (1250 mg/m bid) maintenance therapy administered after 4–6 cycles in- Discussion duction chemotherapy (cisplatin/paclitaxel) vs. best supportive care in newly diagnosed R/M NPC pa- NPC is endemic in southern China and Hong Kong tients. A total of 140 patients were randomized. The with an incidence of approximately 25 cases per primary endpoint was PFS and was met. The PFS 100,000, while it is regarded as an orphan disease in in the capecitabine arm was superior to the SoC the western world [6–8]. In the endemic regions NPC group (35.2 months vs. 9.1 months; HR 0.426; 95% CI is mainly associated with EBV infection, whereas in 0.248–0.731; p = 0.0001). Toxicity was well manageable the USA and Europe alcohol and tobacco use com- in the capecitabine group. prise the major risk factors for NPC development [9, 10]. From this background, it seems obvious why no large randomized phase III studies have been Locally advanced NPC performed outside endemic areas. The current NPC treatment guidelines are mainly based on the evi- Metronomic capecitabine as adjuvant therapy [4] dence generated by clinical trials conducted in Asia The efficacy and safety of metronomic capecitabine resulting in underrepresentation of WHO type I NPC 650 mg/m bid given for up to 1 year vs. obser- patients. vation in patients with locally advanced high-risk In the R/M setting GP is the SoC first-line approach NPC treated with curative chemoradiation was in- irrespective of the subtype resulting in a median PFS vestigated in a randomized controlled phase III trial and OS of 7 and 29 months, respectively [11]. Since presented during the oral abstract session. Stage III- NPC is regarded as an immunogenic malignancy char- 332 ASCO 2021 highlights head and neck cancer: nasopharyngeal carcinoma K short review acterized by high rates of tumor-infiltrating lympho- Funding Open access funding provided by Medical University cytes, multiple single arm phase II studies evaluated of Vienna. the efficacy of immune checkpoint inhibitors such as Conflict of interest T. Fuereder is member of advisory boards pembrolizumab, nivolumab or toripalimab in the sec- and/or received honoraria from MSD, MERCK, Roche, No- ond-line R/M setting [12–16]. Based on the promising vartis, Amgen, Pfizer, BMS and Boehringer Ingelheim, and outcomes of these studies it is not surprising that at- received research funding from MSD and MERCK. tempts have been made to transfer immunotherapy Open Access This article is licensed under a Creative Com- to earlier lines and combine it with chemotherapy. mons Attribution 4.0 International License, which permits Although Jupiter-02 and Captain-1st clearly support use, sharing, adaptation, distribution and reproduction in this approach, a couple of open questions and lim- any medium or format, as long as you give appropriate credit itations remain: (1) The PFS curves overlap during to the original author(s) and the source, provide a link to concurrent immunotherapyplus chemotherapyphase the Creative Commons licence, and indicate if changes were and separate during maintenance therapy. This find- made. The images or other third party material in this article ing suggests that an active comparator such as gem- are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material citabine would have been important in the control is not included in the article’s Creative Commons licence and group. (2) OS data are immature and it is unclear your intended use is not permitted by statutory regulation or whether immunotherapy plus chemotherapy resulted exceeds the permitted use, you will need to obtain permis- in an OS benefit in R/M NPC patients compared to sion directly from the copyright holder. To view a copy of this SoC. (3) Neither toripalimab nor camrelizumab are licence, visit http://creativecommons.org/licenses/by/4.0/. approved outside of Asia and substitution of those agents by any available checkpoint inhibitor does not seem to be justified. References Therefore, the combination of immunotherapy 1. Xu R-H, Mai H-Q, Chen Q-Y, et al. JUPITER-02: Random- with chemotherapy in untreated R/M NPC remains ized,double-blind,phaseIIIstudyoftoripalimaborplacebo investigational until a more widespread regulatory plus gemcitabine and cisplatin as first-line treatment for re- approval and additional follow-up is available. current or metastatic nasopharyngeal carcinoma (NPC). As for high-risk locally advanced NPC, the SoC ap- J Clin Oncol. 2021;39:LBA2. proach (IC followed by chemoradiation [CRT] or CRT 2. Zhang L, Yang Y, Qu S, et al. Camrelizumab versus placebo followed by adjuvant chemotherapy) results in a 3- combined with gemcitabine and cisplatin for recurrent year FFS of approximately 80% [17–19]. Especially the or metastatic nasopharyngeal carcinoma: a randomized, double-blind, phase3 trial. J Clin Oncol. 2021;39:6000. role of adjuvant chemotherapy in patients who did not 3. LiuG-Y,LiW-Z,WangD-S,etal. Capecitabinemaintenance undergo IC is still a matter of debate and associated therapy after induction chemotherapy in newly diagnosed with considerable toxicity. metastatic nasopharyngeal carcinoma: an open-label, ran- Both capecitabine trials presented promising data. domized,controlled,phasetrial. JClinOncol. 2021;39:6044. However, it is surprising that the FFS in the metro- 4. Ma J, Chen Y-P, Sun Y, et al. Metronomic capecitabine as ad- nomic and standard dose capecitabine studies out- juvant therapy in locoregionally advanced nasopharyngeal lined above are comparable despite more intensive carcinoma: a phase 3, multicenter, randomized controlled trial. J Clin Oncol. 2021;39:6003. treatment with IC in the metronomic capecitabine 5. Miao J, Wang L, Tan SH, et al. Adjuvant capecitabine study. To identify patients who derive a benefit from in locoregionally advanced nasopharyngeal carcinoma: a adjuvant capecitabine, use of a predictive biomarker multicenter randomized controlled phase III trial. J Clin is highly desirable. Since a recent study investigating Oncol. 2021;39:6005. the role of postradiation EBV DNA as a biomarker 6. Chang ET, Adami HO. The enigmatic epidemiology of for adjuvant chemotherapy did not show a difference nasopharyngeal carcinoma. Cancer Epidemiol Biomarkers Prev. 2006;15:1765–77. with respect to relapse-free survival, further research 7. Lee AW, Foo W, Mang O, et al. Changing epidemiology is needed and the use of EBV DNA to select patients of nasopharyngeal carcinoma in Hong Kong over a 20- for adjuvant therapy is not recommended outside year period (1980–99): an encouraging reduction in both clinical trials [20]. incidenceandmortality. IntJ Cancer. 2003;103:680–5. 8. Ono T, Azuma K, Kawahara A, et al. Prognostic stratification ofpatientswithnasopharyngealcarcinomabasedontumor Conclusion immunemicroenvironment. HeadNeck. 2018;40:2007–19. 9. Chua MLK, Wee JTS, Hui EP, Chan ATC. Nasopharyngeal Despite its chemo- and radiotherapy-sensitive tumor carcinoma. Lancet. 2016;387:1012–24. biology, the treatment of NPC remains a clinical chal- 10. Vaughan TL, Shapiro JA, Burt RD, et al. Nasopharyngeal lenge. The outcomes in the R/M setting are poor and cancer in a low-risk population: defining risk factors by adjuvant therapy after CRT is not tolerated by the ma- histological type. Cancer Epidemiol Biomarkers Prev. jority of the patients. Therefore, the immunotherapy 1996;5:587–93. and adjuvant capecitabine phase III NPC studies pre- 11. Zhang L, Huang Y, Hong S, et al. Gemcitabine plus cisplatin versus fluorouracil plus cisplatin in recurrent or metastatic sented during the virtual ASCO 2021 conference will nasopharyngeal carcinoma: a multicentre, randomised, potentially change clinical practice depending on the open-label, phase3 trial. Lancet. 2016;388:1883–92. outcomes of longer follow-up. K ASCO 2021 highlights head and neck cancer: nasopharyngeal carcinoma 333 short review 12. Khanna R, Busson P, Burrows SR, et al. Molecular character- 18. Zhang Y, Chen L, Hu GQ, et al. Gemcitabine and cisplatin ization of antigen-processing function in nasopharyngeal induction chemotherapy in nasopharyngeal carcinoma. carcinoma (NPC): evidence for efficient presentation of NEngl J Med. 2019;381:1124–35. Epstein-Barr virus cytotoxic T-cell epitopes by NPC cells. 19. Blanchard P, Lee A, Marguet S, et al. Chemotherapy and ra- Cancer Res. 1998;58:310–4. diotherapy in nasopharyngeal carcinoma: an update of the 13. Pai S, O’Sullivan B, Abdul-Jabbar I, et al. Nasopharyngeal MAC-NPCmeta-analysis. LancetOncol. 2015;16:645–55. carcinoma-associated Epstein-Barr virus-encoded onco- 20. Chan ATC, Hui EP, Ngan RKC, et al. Analysis of plasma gene latent membrane protein 1 potentiates regulatory Epstein-Barr virus DNA in nasopharyngeal cancer after T-cell function. Immunol Cell Biol. 2007;85:370–7. chemoradiation to identify high-risk patients for adjuvant 14. Hsu C, Lee SH, Ejadi S, et al. Safety and antitumor activity chemotherapy: a randomized controlled trial. J Clin Oncol. of pembrolizumab in patients with programmed death- 2018; https://doi.org/10.1200/JCO.2018.77.7847. ligand 1-positive nasopharyngeal carcinoma: results of the Publisher’s Note Springer Nature remains neutral with regard KEYNOTE-028 study. J Clin Oncol. 2017;35(36):4050–6. to jurisdictional claims in published maps and institutional 15. Ma BBY, Lim WT, Goh BC, et al. Antitumor activity of affiliations. nivolumab in recurrent and metastatic nasopharyngeal carcinoma: an international, multicenter study of the mayo clinic phase 2 consortium (NCI-9742). J Clin Oncol. 2018;36:1412–8. 16. Wang FH,Wei XL,Feng J,et al. Efficacy, safety, and 7 For latest news from interna- correlative biomarkers of toripalimab in previously treated tional oncology congresses see: recurrentormetastaticnasopharyngealcarcinoma: aphase http://www.springermedizin.at/ II clinical trial (POLARIS-02). J Clin Oncol. 2021;39:704–12. memo-inoncology 17. Sun Y,Li WF, Chen NY,et al. Induction chemother- apy plus concurrent chemoradiotherapy versus concur- rent chemoradiotherapy alone in locoregionally advanced nasopharyngeal carcinoma: a phase 3, multicentre, ran- domisedcontrolledtrial. LancetOncol. 2016;17:1509–20. 334 ASCO 2021 highlights head and neck cancer: nasopharyngeal carcinoma K

Journal

memo - Magazine of European Medical Oncology – Springer Journals

Published: Dec 1, 2021

Keywords: oncology; medicine/public health, general

There are no references for this article.