SAMO MASTERCLASS HEAD & NECK CANCER Nicolas Mach, PD Geneva University Hospital
Epidemiology Prevention Best treatment for localized disease Best treatment for relapsed or metastatic disease
Introduction Head & Neck cancer SCC salivary gland tumors others: sarcoma, melanoma HNSCC is often neglected compared to more trendy tumors Difficult anatomical region Patient population Treatment related toxicity Often considered poorly responsive to therapy Like most tumor early detection leads to better cure Role of primary care, GP, dentist, H&N specialist
Epidemiology H&N= >53 000 case/y >11 000 death/y USA 2013 H&N >53 000 Incidence > leukemia, lymphoma pancreas, œsophagus, stomac, kidney, thyroid, brain, bladder
Epidemiology Male >>>> Female 7th cause of cancer in men, 13th in female Types of H&N cancer are changing Less laryngeal, hypopharyngeal carcinomas More Oro-pharyngeal cancer Decrease in smoking in the USA in the last 3 decades did translate in less tobacco related H&N cancers but Incidence of HNSCC continue to rise!!!!
Epidemiology
Epidemiology Increase in oropharyngeal ca is due to HPV + tumors Increase in HPV + tumors occurs in male
Epidemiology
Epidemiology At least 2 types of HNSCC Oropharyngeal, Young Male N+ Hypopharynx Larynx Male Smoker +/- alcohol
Three News for H&N cancers 1 Bad News: More and more H&N carcinomas in young non-smokers 2 Good news: New epidemic of oropharyngeal tumors in non smokers has a much better prognostic 3 News: HPV related H&N cancers are mainly a sexually-transmitted diseases
HPV related HNSCC Many questions remains Why occuring predominatly in men not in women? Is it only a sexually transmitted disease? Very high HPV prevalence in boys <10 years old Evidence of HPV+ HNSCC in sexually non-active male Oro-oral contamination documented
HPV + tumors have a better outcome Oropharyngeal tumors treated with CRT
Prevention Tobacco exposure Alcohol consumption HPV infection: Vaccination is available for young women in some countries Not yet for men
Localized Disease Best treatment for locally advanced disease: Stage III (T1N2,T2N2, T3N0-2) or Stage IV (T4anyN, anytn3) -Radiotherapy -Chemo-radiotherapy (CRT) -Surgery followed by Radiotherapy or CRT -Radiotherapy + Cetuximab -Radiotherapy + Cisplatin + Cetuximab -Induction chemotherapy followed by CRT -Induction chemotherapy followed by radiotherapy + cetuximab
Localized Disease Meta-analysis 93 randomized studies >17000 pts treated with radiotherapy and chemotherapy Concomitant CRT is better Cisplatin is the best agent Pignon, May 2009 Radiot &Oncology
Localized Disease Increased toxicity (mucositis, xerostomia, dysphagia) Pignon, 2009
Localized Disease Which patients should receive CRT? Pignon, May 2009
Localized Disease Which patients do not benefit from CRT? < Stage III tumors, Age >70, majors co-morbidities, PS 2 Pignon, May 2009
Can EGFR targeting agents replace chemotherapy? Colorectal Lung (NSCLC) Colorectal cancer (advanced advanced)) 75--82% 75 Lung cancer (NSCLC) 40--91% 40 Head & neck cancer (SCCHN) 9090100% Gastric cancer 33--74% 33 Ovarian cancer 35--70% 35 Head & Neck (SCC) EGFR is widely expressed in H&N cancers
EGFR inhibition NEJM 2008
Localized Disease RTX + moab is better than RTX alone Increased OS Bonner, NEJM 2006 Lancet Oncology 2010
Localized Disease Increased LR control P=0.005 NEJM 2006
Localized Disease Toxicity profile is different No increase in Mucositis or radiation induced Dermatitis in this study Bonner, NEJM 2006
Localized Disease Corelation between skin rash and RTX/Cetuximab efficacy Bonner, Lancet Oncol 2010
Localized Disease Who does benefit from Cetuximab! Non oropharynx Non-USA KPS<90 Age>65 Female T4 /N0 tumors RTX once daily Bonner et al 2010, Lancet Oncol update on survival Oropharynx USA KPS>90 Age<65 Male T1-3 / N1-3 RTX boost
Localized Disease RTX + Cetuximab - Better than RTX alone for oropharyngeal tumor in fit, american young, male, N+ - Is this the profile of the HPV-type HNSCC? - Ongoing study RTOG 10-16 adressing this question CRT vs RT + Cetuximab in HPV+ patients PATIENT S SUBGROUP NOT BENEFITING FROM CRT DO NOT BENEFIT FROM CETUXIMAB EITHER (>70, KPS<90, small tumors)
Localized Disease Chemo-Radiotherapy Vs Radio-Cetuximab Study 1 221 consecutive patients at MSKCC and affiliates hospitals RTX+ Cetux: older, more renal impairement, MSKCC> affiliates
Loco-regional failure All locations Oropharynx Hypopharynx /Larynx
Overall survival All locations Oropharynx Hypopharynx /Larynx
Chemo-radiotherapy Vs Radio-Cetuximab Study 2 Abstract 163 2012 Washington University Retrospective study, 63 pts Not well balanced, (older and less fit patients received Cetux) RTX was delivered similarly in both groups (97% of planned dose) Mean follow-up: 30 months Disease specific survival at 30 months: 79% for RCT vs 27% RT+Cetux Overall survival at 30 months: 72% vs 25% NO EVIDENCE THAT RTX + CETUXIMAB IS AS GOOD AS RTX + CDDP NO EVIDENCE RTX + CETUXIMAB IS FAVORABLE FOR A SUB-GROUP
Localized Disease Chemo-radiotherapy +/- Cetuximab STUDY RTOG 0522 presented ASCO 2011 not yet published 940 HNSCC stage III and IV Median follow-up: 2.4 years PFS at 2 years: 63,4 vs 64,3 % OS: 82,6 vs 79,7 % More toxicity in the Cetuximab arm (dermatitis, mucositis) CONCERT-1 similar randomized Phase 2 LRC at 2 years : Negative study NO EVIDENCE THAT ADDING CETUXIMAB OR PANITUMUMAB TO CRT IS BETTER
Localized Disease Role of Induction chemotherapy TPF vs TP followed by CRT No CRT alone arm
Localized Disease TPF is the best Induction chemotherapy
In 2012: Two Phase III studies comparing CRT with or without IC reported DeCIDE and Pardigm studies
In both studies The addition to IC failed to improved OS or PFS/RFS compaired to CRT alone The addition to IC increased toxicity Enrolment was low and planned accrual was not reached NO EVIDENCE THAT ADDING INDUCTION CHEMOTHERAPY PRIOR TO CRT IS BENEFICIAL
Radio-chemotherapy Vs Radio-Cetuximab +/- Induction No final results yet, ASCO 2013: pooled data A1+B1 vs A2+B2 identical
Relapsing or Metastatic Disease PFS data NEJM 2008
Improved Overall Survival Toxicities: rash, hypomg, allergic reactions CT + CETUXIMAB IS THE BEST TREATMENT FOR LOCAL RELAPSE OR M+ Vermorken, NEJM 2008
HNSCC are common cancers Early detection is key for curative treatment HNSCC is not a single disease Decrease in smoking-related HNSCC More Oropharyngeal tumors related to HPV exposure HPV + HNSCC is a distinct entity / better prognostic? Can we de-escalate treatment for HPV tumor??are moab equal/better than chemo in HPV + tumors?? Should we recommend HPV vaccine for men?
RTX + Cetuximab is better than RTX alone For stage III-IV: CRT is the standard of care Cetuximab can not substitute for Cisplatin Adding moab to CRT is not efficient Induction chemotherapy is not a standard of care Cetuximab + chemo. improves OS in M+/ LR setting Many ongoing trials with news compounds PI3K inhibitors, therapeutic vaccines, PD-1 /PDL-1inhibitors, etc