Upload
others
View
6
Download
0
Embed Size (px)
Citation preview
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?