What’s left of chemotherapy?
Orazio Caffo
• From the accidental discovery of therapeutic effect of sulfur mustards, CT was for decades the only anticancer strategy
• The HT was discovered to be as an efficacious alternative but only for few hormone-sensitive cancers
• Today, it appears that the maximum level of CT efficacy was reached and novel anticancer strategies 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 produced disappointing OS outcomes
The case of hormone-dependent tumors:
breast cancer
• CT was historically considered as an alternative mainly in tumors with aggressive features or which were (or became) resistent to the anti-hormonal agents
The case of hormone-dependent tumors:
prostate cancer
• HT was historically considered the reference treatment for this tumor with poor OS outcomes 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 3rdline Enzalutamide
ADT
mCRPC
Enzalutamide
Cabazitaxel
Abiraterone Abiraterone
Docetaxel
Ra 223*
nmCSPC
mCRPC nmCRPC
mCSPC
* from 3rdline Enzalutamide
Docetaxel
ADT
mCRPC
Enzalutamide
Cabazitaxel
Abiraterone Abiraterone
Docetaxel
Ra 223*
nmCSPC
mCRPC nmCRPC
mCSPC
* from 3rdline Enzalutamide
Enzalutamide
Apalutamide
Darolutamide
Abiraterone
Docetaxel
Enzalutamide
Apalutamide
The case of CT mildly-sensitive tumors:
NSCLC
• Chemotherapy was historically the reference treatment for this cancer
• The OS outcomes were disappointing
months
4,96
7,22 7,77
8,66 9,17
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 reference treatment for this cancer
• The OS outcomes were disappointing (mainly in platinum-refractory pts)
The case of CT mildly-sensitive tumors:
colorectal cancer
• Chemotherapy was historically the reference treatment for this cancer
• Our ability to chronicize the metastatic disease was partially achieved
Conclusions
• Scientific achievements and regulatory enhancements have resulted in a dramatic increase in targeted and immunologic cancer drug approvals.
• The resulting change in clinical guidelines has caused some to posit a chemotherapy-free future for cancer treatment.
• The realities of disease natural history, current practice, and ongoing clinical trials suggest that such a future is much further off.
• As long as chemotherapy remains critical to cancer treatment, additional research is needed to increase its patient-centricity.
