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TRANSCRIPT
What’s left of chemotherapy?
Orazio Caffo
• From the accidental discovery of therapeuticeffect of sulfur mustards, CT was for decades theonly anticancer strategy
• The HT was discovered to be as an efficaciousalternative but only for few hormone-sensitivecancers
• Today, it appears that the maximum level of CTefficacy was reached and novel anticancerstrategies are being explored
The case of adjuvant RXs
Cancer Proposable adjuvant RXs
Breast CT / HT* / TT**
Colon/rectum CT
Lung CT
Ovary CT
Brain CT
Kidney NA
Testis CT
Prostate HT
* only ER+ pts** only HER+ pts in combination with CT
The case of “chemo-resistant”tumors:renal cancer
• In renal cancer evidences never supported the use of CT in these tumors
The case of “chemo-resistant”tumors:melanoma
• CT use in pts with melanoma produceddisappointing OS outcomes
The case of hormone-dependent tumors:breast cancer
• CT was historically considered as analternative mainly in tumors with aggressivefeatures or which were (or became) resistentto the anti-hormonal agents
The case of hormone-dependent tumors:prostate cancer
• HT was historically considered the referencetreatment for this tumor with poor OSoutcomes when the disease became“hormone-resistant”
• CT led to an OS gain in HRPC cancer
ADT
mCRPC
Enzalutamide
Cabazitaxel
Abiraterone
Abiraterone
Docetaxel
Ra 223*
nmCSPC
mCRPC
nmCRPC
mCSPC
* from 3rd line
Enzalutamide
ADT
mCRPC
Enzalutamide
Cabazitaxel
Abiraterone
Abiraterone
Docetaxel
Ra 223*
nmCSPC
mCRPC
nmCRPC
mCSPC
* from 3rd line
Enzalutamide
Docetaxel
ADT
mCRPC
Enzalutamide
Cabazitaxel
Abiraterone
Abiraterone
Docetaxel
Ra 223*
nmCSPC
mCRPC
nmCRPC
mCSPC
* from 3rd line
Enzalutamide
Enzalutamide
Apalutamide
Darolutamide
Abiraterone
Docetaxel
Enzalutamide
Apalutamide
The case of CT mildly-sensitive tumors:NSCLC
• Chemotherapy was historically the referencetreatment for this cancer
• The OS outcomes were disappointing
months
4,96
7,227,77
8,669,17
8,6
0
1
2
3
4
5
6
7
8
9
10
BSC 1995-2001 P alone PE Old Cis + no PE New Cis + Carbo +
+45,5%
+11%
+17,9%
+10,2% -11,4%
CT-related OS gains
Mhanna L et al. Curr. Treat. Options in Oncol. (2019) 20: 60
Duchemann B et al Eur Resp J 2015
Wu, SG. & Shih, JY. Mol Cancer (2018) 17: 38
The case of CT mildly-sensitive tumors:ovarian cancer
• Chemotherapy was historically the referencetreatment for this cancer
• The OS outcomes were disappointing (mainlyin platinum-refractory pts)
The case of CT mildly-sensitive tumors:colorectal cancer
• Chemotherapy was historically the referencetreatment for this cancer
• Our ability to chronicize the metastaticdisease was partially achieved
Conclusions
• Scientific achievements and regulatory enhancementshave resulted in a dramatic increase in targeted andimmunologic cancer drug approvals.
• The resulting change in clinical guidelines has causedsome to posit a chemotherapy-free future for cancertreatment.
• The realities of disease natural history, current practice,and ongoing clinical trials suggest that such a future ismuch further off.
• As long as chemotherapy remains critical to cancertreatment, additional research is needed to increase itspatient-centricity.