what is new in anal cancer in the last 12 months · • ~ 70% of squamous histology • hpv...
TRANSCRIPT
![Page 1: What is new in anal cancer in the last 12 months · • ~ 70% of squamous histology • HPV infection detected in 80%-90% of cases • Only a few standard options especially when](https://reader034.vdocuments.net/reader034/viewer/2022050405/5f823d5a22ee50161a2f9667/html5/thumbnails/1.jpg)
What is new in anal cancer in the last 12 months
Michel Ducreux, MD, PhDChef du Service d’Oncologie Digestive
Département de Médecine Oncologique
![Page 2: What is new in anal cancer in the last 12 months · • ~ 70% of squamous histology • HPV infection detected in 80%-90% of cases • Only a few standard options especially when](https://reader034.vdocuments.net/reader034/viewer/2022050405/5f823d5a22ee50161a2f9667/html5/thumbnails/2.jpg)
Anal cancer: Epidemiology and treatment
• Relatively rare cancer – incidence : ~1-2 cases/100 000 worldwide1
• Increasing incidence by 1%-3% per year in developpedcountries
• ~ 70% of squamous histology• HPV infection detected in 80%-90% of cases• Only a few standard options especially when :
– The disease recurs after radio-chemotherapy– In metastatic setting
1Grulich AE et al. Sex Health 2012;9:504-82NCCN Guidelines for the treatment of Anal Canal Carcinoma
![Page 3: What is new in anal cancer in the last 12 months · • ~ 70% of squamous histology • HPV infection detected in 80%-90% of cases • Only a few standard options especially when](https://reader034.vdocuments.net/reader034/viewer/2022050405/5f823d5a22ee50161a2f9667/html5/thumbnails/3.jpg)
Active drugs in advanced anal canal cancer: an unmet need!
![Page 4: What is new in anal cancer in the last 12 months · • ~ 70% of squamous histology • HPV infection detected in 80%-90% of cases • Only a few standard options especially when](https://reader034.vdocuments.net/reader034/viewer/2022050405/5f823d5a22ee50161a2f9667/html5/thumbnails/4.jpg)
Active drugs in advanced anal canal cancer: an unmet need!
![Page 5: What is new in anal cancer in the last 12 months · • ~ 70% of squamous histology • HPV infection detected in 80%-90% of cases • Only a few standard options especially when](https://reader034.vdocuments.net/reader034/viewer/2022050405/5f823d5a22ee50161a2f9667/html5/thumbnails/5.jpg)
CHEMOTHERAPY
![Page 6: What is new in anal cancer in the last 12 months · • ~ 70% of squamous histology • HPV infection detected in 80%-90% of cases • Only a few standard options especially when](https://reader034.vdocuments.net/reader034/viewer/2022050405/5f823d5a22ee50161a2f9667/html5/thumbnails/6.jpg)
A recent review:
Morris VK and Eng C: Surg Oncol Clin N Am 2017;26:133 - 42
![Page 7: What is new in anal cancer in the last 12 months · • ~ 70% of squamous histology • HPV infection detected in 80%-90% of cases • Only a few standard options especially when](https://reader034.vdocuments.net/reader034/viewer/2022050405/5f823d5a22ee50161a2f9667/html5/thumbnails/7.jpg)
ASCO 2018: FOLFCIS• FOLFCIS, which is essentially FOLFOX with cisplatin
substituted for oxaliplatin, • 53 AC patients (48 metastatic; 5 unresectable, locally
advanced) Median age: 59 years, 32% had metastatic disease at diagnosis
• 41 AC patients underwent targeted NGS• PFS: 7.1 months (95% CI, 4.4 - 8.6) OS: 22.1 months
(95% CI, 16.9 - 28.1)• Most frequent genomic alterations consisted of
chromosome 3q amplification (17%) and mutations in PIK3CA (24%) and KMT2D (24%).
• Genomic alterations of the phosphatidylinositol 3-kinase pathway in PIK3CA, PTEN, or AKT2 54% of cases
Mondaca S et al J Clin Oncol 2018;36:suppl, 3567
![Page 8: What is new in anal cancer in the last 12 months · • ~ 70% of squamous histology • HPV infection detected in 80%-90% of cases • Only a few standard options especially when](https://reader034.vdocuments.net/reader034/viewer/2022050405/5f823d5a22ee50161a2f9667/html5/thumbnails/8.jpg)
IRCI anal cancer metastatic trial
![Page 9: What is new in anal cancer in the last 12 months · • ~ 70% of squamous histology • HPV infection detected in 80%-90% of cases • Only a few standard options especially when](https://reader034.vdocuments.net/reader034/viewer/2022050405/5f823d5a22ee50161a2f9667/html5/thumbnails/9.jpg)
TARGETED THERAPIES
![Page 10: What is new in anal cancer in the last 12 months · • ~ 70% of squamous histology • HPV infection detected in 80%-90% of cases • Only a few standard options especially when](https://reader034.vdocuments.net/reader034/viewer/2022050405/5f823d5a22ee50161a2f9667/html5/thumbnails/10.jpg)
Cetuximab + CT-RT in immunocompetent patients
Garg MK et al. J Clin Oncol 2017;35:718-26
![Page 11: What is new in anal cancer in the last 12 months · • ~ 70% of squamous histology • HPV infection detected in 80%-90% of cases • Only a few standard options especially when](https://reader034.vdocuments.net/reader034/viewer/2022050405/5f823d5a22ee50161a2f9667/html5/thumbnails/11.jpg)
Cetuximab + CT-RT in immunocompetent patients
• 61 patients• Approximately 20% of local regional failure versus
35%(historical control)… but
Garg MK et al. J Clin Oncol 2017;35:718-26
![Page 12: What is new in anal cancer in the last 12 months · • ~ 70% of squamous histology • HPV infection detected in 80%-90% of cases • Only a few standard options especially when](https://reader034.vdocuments.net/reader034/viewer/2022050405/5f823d5a22ee50161a2f9667/html5/thumbnails/12.jpg)
Cetuximab + RT-CT inHIV-associated anal carcinoma
Sparano JA et al. J Clin Oncol 2017;35:727-33
![Page 13: What is new in anal cancer in the last 12 months · • ~ 70% of squamous histology • HPV infection detected in 80%-90% of cases • Only a few standard options especially when](https://reader034.vdocuments.net/reader034/viewer/2022050405/5f823d5a22ee50161a2f9667/html5/thumbnails/13.jpg)
Cetuximab + RT-CT inHIV-associated anal carcinoma
• 20% LRF only but
Sparano JA et al. J Clin Oncol 2017;35:727-33
![Page 14: What is new in anal cancer in the last 12 months · • ~ 70% of squamous histology • HPV infection detected in 80%-90% of cases • Only a few standard options especially when](https://reader034.vdocuments.net/reader034/viewer/2022050405/5f823d5a22ee50161a2f9667/html5/thumbnails/14.jpg)
Cetuximab in metastatic disease: only a few series
• MD Anderson1
– 17 patients, progression after one line of treatment for metastaticdisease, cetuximab or panitumumab with different CT
– 6 / 17 radiological response (ORR = 35%)
• Manheim2
– 5 patients with Ras wild tye cancer: cetuximab with or withoutirinotecan: 3 / 5 PR
• Gustave Roussy3
– 10 patients,75% HPV+– Folfiri cetuximab in all, median previous lines: 2 [1 – 3]– Median number of cycles: 8 [1 – 23]– 9 evaluable for response : 1 CR, 4 PR (55% ORR)– Median SSP: 5.1 months, median OS: 10.8 months
1Rogers JE et al. Anticancer Drug 2016;27:804-8; 2Lukan N et al. Oncology 2009;77:293-93Malka D et al. 2017. JFHOD 2017 abstracts
![Page 15: What is new in anal cancer in the last 12 months · • ~ 70% of squamous histology • HPV infection detected in 80%-90% of cases • Only a few standard options especially when](https://reader034.vdocuments.net/reader034/viewer/2022050405/5f823d5a22ee50161a2f9667/html5/thumbnails/15.jpg)
An example of response
Patient #9
Patient #1
Patient #10
Malka D et al. 2017 JFHOD abstracts
![Page 16: What is new in anal cancer in the last 12 months · • ~ 70% of squamous histology • HPV infection detected in 80%-90% of cases • Only a few standard options especially when](https://reader034.vdocuments.net/reader034/viewer/2022050405/5f823d5a22ee50161a2f9667/html5/thumbnails/16.jpg)
IMMUNOTHERAPY
![Page 17: What is new in anal cancer in the last 12 months · • ~ 70% of squamous histology • HPV infection detected in 80%-90% of cases • Only a few standard options especially when](https://reader034.vdocuments.net/reader034/viewer/2022050405/5f823d5a22ee50161a2f9667/html5/thumbnails/17.jpg)
Nivolumab: only one phase II study
• Nivolumab: 3 mg/kg/15 jours• Population :
– 37 patients, – 12 men, 25 women, – 1 to 8 lines of previous treatment, – HPV and/or HIV positivity allowed
Morris VK et al Lancet Oncol 2017;18:446-53
![Page 18: What is new in anal cancer in the last 12 months · • ~ 70% of squamous histology • HPV infection detected in 80%-90% of cases • Only a few standard options especially when](https://reader034.vdocuments.net/reader034/viewer/2022050405/5f823d5a22ee50161a2f9667/html5/thumbnails/18.jpg)
Phase II nivolumab: Patients characteristics
![Page 19: What is new in anal cancer in the last 12 months · • ~ 70% of squamous histology • HPV infection detected in 80%-90% of cases • Only a few standard options especially when](https://reader034.vdocuments.net/reader034/viewer/2022050405/5f823d5a22ee50161a2f9667/html5/thumbnails/19.jpg)
Efficacy results
Morris VK et al Lancet Oncol 2017;18:446-53
RESPONSE RATE:• 9 / 37; 24%• 95%CI: [15 – 33]
![Page 20: What is new in anal cancer in the last 12 months · • ~ 70% of squamous histology • HPV infection detected in 80%-90% of cases • Only a few standard options especially when](https://reader034.vdocuments.net/reader034/viewer/2022050405/5f823d5a22ee50161a2f9667/html5/thumbnails/20.jpg)
Efficacy results
Morris VK et al Lancet Oncol 2017;18:446-53
![Page 21: What is new in anal cancer in the last 12 months · • ~ 70% of squamous histology • HPV infection detected in 80%-90% of cases • Only a few standard options especially when](https://reader034.vdocuments.net/reader034/viewer/2022050405/5f823d5a22ee50161a2f9667/html5/thumbnails/21.jpg)
Survival
Progression-free survivalMedian = 4.1 months
Overall survivalMedian = 11.5 months
Morris VK et al Lancet Oncol 2017;18:446-53
![Page 22: What is new in anal cancer in the last 12 months · • ~ 70% of squamous histology • HPV infection detected in 80%-90% of cases • Only a few standard options especially when](https://reader034.vdocuments.net/reader034/viewer/2022050405/5f823d5a22ee50161a2f9667/html5/thumbnails/22.jpg)
KEYNOTE-028: Phase 1b multicohortstudy of pembrolizumab for PDL1+
advanced solid tumors
• Response assessment: every 8 weeks for the first 6 months; every 12 weeks thereafter
• Primary endpoint: ORR per RECIST v1.1• Secondary endpoints: PFS, OS, duration of response, and safety
Ott P et al. Ann Oncol 2017;28:1036-41
![Page 23: What is new in anal cancer in the last 12 months · • ~ 70% of squamous histology • HPV infection detected in 80%-90% of cases • Only a few standard options especially when](https://reader034.vdocuments.net/reader034/viewer/2022050405/5f823d5a22ee50161a2f9667/html5/thumbnails/23.jpg)
Analysis of PD-L1 expression
• Tumor samples: archival or newly obtained core or excisionalbiopsy of non irradiated lesion
• Immunohistochemistry: assessed at a central laboratory• Positivity: membranous PD-L1 expression in >1% of cells in
tumor and stroma
Ott P et al. Ann Oncol 2017;28:1036-41
![Page 24: What is new in anal cancer in the last 12 months · • ~ 70% of squamous histology • HPV infection detected in 80%-90% of cases • Only a few standard options especially when](https://reader034.vdocuments.net/reader034/viewer/2022050405/5f823d5a22ee50161a2f9667/html5/thumbnails/24.jpg)
PD-L1 screening Keynote 28
Ott P et al. Ann Oncol 2017;28:1036-41
![Page 25: What is new in anal cancer in the last 12 months · • ~ 70% of squamous histology • HPV infection detected in 80%-90% of cases • Only a few standard options especially when](https://reader034.vdocuments.net/reader034/viewer/2022050405/5f823d5a22ee50161a2f9667/html5/thumbnails/25.jpg)
Baseline characteristicsCharacteristics N=25
Median age, years (range) 63 (46 – 82)
Female 23 (92)
RaceWhiteBlack or AfricanAmericanNot specified
19 (76)1 (4)
5 (20)
ECOG performance status01
5 (20)20 (80)
Histology at baseline, n (%)Squamous cell carcinomaPerineal epidermoidcarcinoma
24 (96)
1 (4)
Characteristics N=25
Adjuvant or neoadjuvant systemic therapy, n (%)
6 (24)
Prior lines of therapy for advanced disease
012>3Unknown
3 (12)7 (28)6 (24)7 (28)2 (8)
Prior therapies for advanceddisease5FU + mitomycin5FU + platinum + otherGemcitabine + platinum + otherChk-1 inhibitorEtirinotecan pegolOther
15 (60)12 (48)4 (16)2 (8)2 (8)
10 (40)
Ott P et al. Ann Oncol 2017;28:1036-41
![Page 26: What is new in anal cancer in the last 12 months · • ~ 70% of squamous histology • HPV infection detected in 80%-90% of cases • Only a few standard options especially when](https://reader034.vdocuments.net/reader034/viewer/2022050405/5f823d5a22ee50161a2f9667/html5/thumbnails/26.jpg)
Toxicity
Ott P et al. Ann Oncol 2017;28:1036-41
![Page 27: What is new in anal cancer in the last 12 months · • ~ 70% of squamous histology • HPV infection detected in 80%-90% of cases • Only a few standard options especially when](https://reader034.vdocuments.net/reader034/viewer/2022050405/5f823d5a22ee50161a2f9667/html5/thumbnails/27.jpg)
Efficacy data
• 4 partial response, ORR = 17%• 10 stable disease (42%)• 1 not assessed
Ott P et al. Ann Oncol 2017;28:1036-41
![Page 28: What is new in anal cancer in the last 12 months · • ~ 70% of squamous histology • HPV infection detected in 80%-90% of cases • Only a few standard options especially when](https://reader034.vdocuments.net/reader034/viewer/2022050405/5f823d5a22ee50161a2f9667/html5/thumbnails/28.jpg)
Longitudinal change from Baseline in Tumor Size
Ott P et al. Ann Oncol 2017;28:1036-41
![Page 29: What is new in anal cancer in the last 12 months · • ~ 70% of squamous histology • HPV infection detected in 80%-90% of cases • Only a few standard options especially when](https://reader034.vdocuments.net/reader034/viewer/2022050405/5f823d5a22ee50161a2f9667/html5/thumbnails/29.jpg)
Longitudinal change from Baseline in Tumor Size
Ott P et al. Ann Oncol 2017;28:1036-41
![Page 30: What is new in anal cancer in the last 12 months · • ~ 70% of squamous histology • HPV infection detected in 80%-90% of cases • Only a few standard options especially when](https://reader034.vdocuments.net/reader034/viewer/2022050405/5f823d5a22ee50161a2f9667/html5/thumbnails/30.jpg)
BIOLOGY…
![Page 31: What is new in anal cancer in the last 12 months · • ~ 70% of squamous histology • HPV infection detected in 80%-90% of cases • Only a few standard options especially when](https://reader034.vdocuments.net/reader034/viewer/2022050405/5f823d5a22ee50161a2f9667/html5/thumbnails/31.jpg)
Comprehensive genomic profiling of metastatic squamous cell carcinoma of
the anal canal
Morris V et al. Mol Cancer Res 2017;15:1542-50
![Page 32: What is new in anal cancer in the last 12 months · • ~ 70% of squamous histology • HPV infection detected in 80%-90% of cases • Only a few standard options especially when](https://reader034.vdocuments.net/reader034/viewer/2022050405/5f823d5a22ee50161a2f9667/html5/thumbnails/32.jpg)
Conclusion
• Nothing has recently changed in the treatment of metastatic anal canal cancer
• But changes are coming…– New backbone of chemotherapy??– A role to define for targeted therapies
• Anti-EGFR: small series, promising results in metastatic disease
– Role of immunotherapy++++• 25 to 30% of refractory patients benefit from anti PD1• Selection of these patients?