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Printable Handouts
Navigable Slide Index
- Introduction
- Immunotherapy
- Going deep with checkpoint inhibitors
- Mutational burden in cancer
- Immunotherapy in breast cancer (1)
- Immunotherapy in breast cancer (2)
- PD-1/PD-L1 pathway
- Checkpoint inhibitor monotherapy: modest activity
- Monotherapy activity for metastatic TNBC
- Overall survival by response
- Clinical activity of Atezolizumab monotherapy
- Higher ORR and OS with higher TIL infiltration
- Checkpoint inhibitor monotherapy
- Immunotherapy in breast cancer
- How can we augment the immune response?
- Atezolizumab + nab-Paclitaxel
- IMpassion130 study design
- IMpassion130 results: PFS/OS in IIT/PD-L1+
- IMpassion130: PFS subgroup analysis
- IMpassion130: response data
- IMpassion130: safety summary
- IMpassion130: AESIs
- First FDA approval of immunotherapy in BC
- Questions that arise post IMpassion130 (1)
- TONIC trial
- Phase Ib/II study of Eribulin with Pembrolizumab
- ENHANCE-1: Eribulin + Pembrolizumab efficacy
- KN355 study schema – phase III study
- Contessa trio: study design
- Questions that arise post IMpassion130 (2)
- IMpassion130: PDL1 status
- PD-L1 IHC staining
- IMpassion130: PD-L1 expressed mainly on IC
- Atezolizumab in combination with nab-Paclitaxel
- Differences between primary and metastatic tumor
- Questions that arise post IMpassion130 (3)
- The future – novel combinations in all subtypes
- Enhancing response to checkpoint inhibition
- Combination plus immunotherapy in ER+ BC
- Mutational load by subtype: lower in ER+ disease
- Distribution of TILs in different BC subtypes
- TILs are linked to increased pCR rates
- TILs and prognosis in different subtypes
- Immune checkpoint inhibitors in HR+ disease
- I-SPY2 trial
- Immune biomarkers and response in I-SPY2
- Immune-related adverse events
- Differences in toxicity between inhibitors?
- Phase 2 study of Eribulin ± Pembrolizumab
- CDK4/6 inhibitors: trigger anti-tumor immunity
- JPCE trial
- JPCE: response summary
- Will immunotherapy have a role in HER2+ BC?
- Study design: PANACEA
- Best overall response (RECIST 1.1)
- PFS and OS
- KATE2: T-DM1 + Atezolizumab (1)
- KATE2: T-DM1 + Atezolizumab (2)
- TBCRC 045: AVIATOR Trial
- Can immunotherapy improve outcomes?
- Can immunotherapy improve activity?
- Can we use other combinations to enhance activity
- PARP may enhance immune activation
- TOPACIO study design
- TOPACIO: efficacy
- MEDIOLA: schema for third stage
- ETCTN trial: NCI 10020
- Can AKT inhibition act synergistically?
- PTEN loss associated with worse PFS and OS
- Adding AKT inhibiton
- Summary
- Case 1
- Case 2
Topics Covered
- Checkpoint inhibitor therapy in breast cancer: focus on TNBC
- Limited activity for checkpoint inhibitor monotherapy in metastatic TNBC
- Atezolizumab + Nab-Paclitaxel: standard first line therapy for patients with metastatic PDL1 and
- Combination treatment with checkpoint inhibitor therapy in HR+ and HER2+ breast cancer
- Ongoing studies evaluating other strategies in breast cancer
- The future: combination of checkpoint inhibitors and chemotherapy
Links
Series:
Categories:
Therapeutic Areas:
Talk Citation
Tolaney, S.M. (2019, July 31). Immunotherapy: insights from advanced disease [Video file]. In The Biomedical & Life Sciences Collection, Henry Stewart Talks. Retrieved December 21, 2024, from https://doi.org/10.69645/VNFJ6476.Export Citation (RIS)
Publication History
Financial Disclosures
- Dr. Sara M. Tolaney is a study(s) PI and/or consultant and/or on the advisory board of the following companies, and accordingly receiving research funding and/or honoraria from: AstraZeneca, Lilly, Merck, Nektar, Novartis, Pfizer, Genentech/Roche, Immunomedics, Exelixis, Bristol-Myers Squibb, Eisai, Nanostring, Puma, Cyclacel, Sanofi, Tesaro, Celldex, Paxman and Seattle Genetics.
Other Talks in the Series: Periodic Reports: Advances in Clinical Interventions and Research Platforms
Transcript
Please wait while the transcript is being prepared...
0:00
My name is Sara Tolaney.
I'm a breast medical oncologist at the Dana-Farber Cancer Institute.
Today I'm going to be reviewing immunotherapy for the treatment
of breast cancer, with insights from the advanced disease setting.
0:14
Immunotherapy has really been
a paradigm shift in the way that we approach treatment for cancer.
It allows us to utilize the patient's own immune system to target
their malignancy and allows for the potential for long duration responses.
It's been generally associated with lower rates of
toxicity than we've previously seen with chemotherapy,
and it allows us to utilize a smart strategy to
overcome the molecular complexity of cancer.
0:42
Immunotherapy has been successful in the treatment of both hematologic and solid tumors,
and very recently we've achieved the first FDA approval for
immunotherapy in metastatic triple-negative breast cancer,
with the combination of nab-paclitaxel and atezolizumab.
0:60
Development of immunotherapy in breast cancer has been
more challenging than it has been in some other solid tumors.
One reason for this may be that breast cancer is associated with
a lower tumor mutational burden than we've seen
in cancers where immunotherapy has been quite successful,
such as melanoma and lung cancer.
If you can see here on this chart that both melanoma and
lung cancer are associated with very high tumor mutational burdens.
Whereas breast cancer has been associated with
much lower rates of tumor mutational burden.
This may be why we see
less neoantigen production and less stimulation of the immune system.
1:39
Most of the work focusing on immunotherapy in
breast cancer has initially been in the triple-negative setting.
The reasons for this are that triple-negative breast cancer has been
associated with relatively higher mutational load compared to
hormone receptor positive and HER2 positive disease,
is associated with higher levels of
tumor infiltrating lymphocytes, and has higher rates of
PD-L1 positivity compared to the other two sub-types.