What is new in anal cancer in the last
12 months
Michel Ducreux, MD, PhD
Chef du Service d’Oncologie Digestive
Département de Médecine Oncologique
Anal cancer: Epidemiology and
treatment
• Relatively rare cancer – incidence : ~1-2 cases/100 000
worldwide1
• Increasing incidence by 1%-3% per year in developped
countries
• ~ 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
Active drugs in advanced anal
canal cancer: an unmet need!
CHEMOTHERAPY
A recent review:
Morris VK and Eng C: Surg Oncol Clin N Am 2017;26:133 - 42
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
IRCI anal cancer metastatic trial
TARGETED THERAPIES
Cetuximab + CT-RT in
immunocompetent patients
Garg MK et al. J Clin Oncol 2017;35:718-26
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
Cetuximab + RT-CT inHIV-
associated anal carcinoma
Sparano JA et al. J Clin Oncol 2017;35:727-33
Cetuximab + RT-CT inHIV-
associated anal carcinoma
• 20% LRF only but
Sparano JA et al. J Clin Oncol 2017;35:727-33
Cetuximab in metastatic disease:
only a few series
• MD Anderson1
– 17 patients, progression after one line of treatment for metastatic
disease, cetuximab or panitumumab with different CT
– 6 / 17 radiological response (ORR = 35%)
• Manheim2
– 5 patients with Ras wild tye cancer: cetuximab with or without
irinotecan: 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. Anicancer Drug 2016;27:804-8; 2Lukan N et al. Oncology 2009;77:293-93Malka D et al. 2017. JFHOD 2017 abstracts
An example of response
Paient #9
Paient #1
Paient #10
Malka D et al. 2017 JFHOD abstracts
IMMUNOTHERAPY
Nivolumab: only one phase II study
• Nivolumab: 3 mg/kg/15 jours
• Populaion :
– 37 paients,
– 12 men, 25 women,
– 1 to 8 lines of previous treatment,
– HPV and/or HIV posiivity allowed
Morris VK et al Lancet Oncol 2017;18:446-53
Phase II nivolumab: Patients
characteristics
Efficacy results
Morris VK et al Lancet Oncol 2017;18:446-53
RESPONSE RATE:
• 9 / 37; 24%• 95%CI: [15 – 33]
Efficacy results
Morris VK et al Lancet Oncol 2017;18:446-53
Survival
Progression-free survival
Median = 4.1 months
Overall survival
Median = 11.5 months
Morris VK et al Lancet Oncol 2017;18:446-53
KEYNOTE-028: Phase 1b multicohort study of
pembrolizumab for PDL1+ advanced solid
tumors
• Response assessment: every 8 weeks for the irst 6 months; every 12
weeks thereater
• Primary endpoint: ORR per RECIST v1.1
• Secondary endpoints: PFS, OS, duraion of response, and safety
Ot P et al. Ann Oncol 2017;28:1036-41
Analysis of PD-L1 expression
• Tumor samples: archival or newly obtained core or excisional
biopsy of non irradiated lesion
• Immunohistochemistry: assessed at a central laboratory
• Posiivity: membranous PD-L1 expression in >1% of cells in
tumor and stroma
Ot P et al. Ann Oncol 2017;28:1036-41
PD-L1 screening Keynote 28
Ot P et al. Ann Oncol 2017;28:1036-41
Baseline characteristics
Characterisics N=25
Median age, years (range) 63 (46 – 82)
Female 23 (92)
RaceWhiteBlack or African AmericanNot speciied
19 (76)1 (4)
5 (20)
ECOG performance status01
5 (20)20 (80)
Histology at baseline, n (%)Squamous cell carcinomaPerineal epidermoid carcinoma
24 (96)
1 (4)
Characterisics 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 advanced disease5FU + mitomycin5FU + plainum + otherGemcitabine + plainum + otherChk-1 inhibitorEirinotecan pegolOther
15 (60)12 (48)4 (16)2 (8)2 (8)
10 (40)
Ot P et al. Ann Oncol 2017;28:1036-41
Toxicity
Ot P et al. Ann Oncol 2017;28:1036-41
Efficacy data
• 4 parial response, ORR = 17%
• 10 stable disease (42%)
• 1 not assessed
Ot P et al. Ann Oncol 2017;28:1036-41
Longitudinal change from Baseline
in Tumor Size
Ot P et al. Ann Oncol 2017;28:1036-41
BIOLOGY…
Comprehensive genomic profiling of metastatic
squamous cell carcinoma of the anal canal
Morris V et al. Mol Cancer Res 2017;15:1542-50
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?