Lajos Pusztai, M.D, D.Phil. Professor of Medicine Director, Breast Cancer Translational Research Co-Director, Yale Cancer Center Genetics and Genomics Program Yale Cancer Center Yale School of Medicine

Breast Cancer: Cost-Effectiveness of Neoadjuvant-Adjuvant Treatment Strategies

MedicalResearch.com Interview with:

Lajos Pusztai, M.D, D.Phil. Professor of Medicine Director, Breast Cancer Translational Research Co-Director, Yale Cancer Center Genetics and Genomics Program Yale Cancer Center Yale School of Medicine

Dr. Pusztai

Lajos Pusztai, M.D, D.Phil.
Professor of Medicine
Director, Breast Cancer Translational Research
Co-Director, Yale Cancer Center Genetics and Genomics Program
Yale Cancer Center
Yale School of Medicine

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: In HER2-positive early stage (stage I-II) breast cancer, several different preoperative (also called neoadjuvant) chemotherapy options exist, each of these is associated with a different rate of complete eradication of cancer from the breast and lymph nodes (called pathologic complete response or pCR). Patients who experience pCR have excellent long term survival. The complete response rates range from 20% to 80%, the rates are higher with regimens that include several different chemotherapy drugs and dual HER2 blockade. Unfortunately, these highly effective multi-drug treatment regimens are also more toxic and more expensive. We also learned that patients who do not achieve pCR after preoperative therapy, have high rates of recurrence, but the recurrence rate can be improved by administering postoperative adjuvant therapy.

These two observations together, (1) different regimens with different toxicities and costs resulting in different pCR rates, and (2) existence of effective postoperative therapies for patients with residual cancer after preoperative therapy, sets the stage for combining various pre- and post-operative treatment strategies. Starting with a shorter, less toxic and less expensive neoadjuvant regimen would allow a substantial minority (20-45%) of patients who archive pCR to be spared of longer and more toxic regimens, whereas those with residual disease could receive the remaining part of the currently most effective regimens post-operatively as adjuvant therapy.

In this study we examined the cost effectiveness of different neoadjuvant followed by adjuvant treatment strategies from a healthcare payer perspective.

MedicalResearch.com: What should readers take away from your report?

Response: In our analyses, we assumed that

(i) breaking up a sequential, multi-drug regimen into a pre- and a post-operative component will result in the same overall outcome as administering all the treatment preoperatively,

(ii) patients who achieve a pCR will have similarly good prognosis regardless of what regimen, or component of a regimen, induced the pCR.

We examined the cost effectiveness of several treatment strategies that employ clinically relevant and practically doable treatments.

We considered 4 neoadjuvant treatment regimen including

(1): HP: trastuzumab (H)+pertuzumab (P);
(2) THP: paclitaxel (T)+H+P triplet;
(3) ddAC/THP: dose dense anthracycline/cyclophosphamide (ddAC)+THP;
(4) TCHP: docetaxel (T)+carboplatin (C)+HP,

and 4 adjuvant treatments for patients with residual disease:

  1. H alone;
  2. T-DM1;
  3. ddAC/THP+T-DM1;
  4. ddAC+T-DM1.

All patients with pCR received adjuvant H, patients with RD received the following therapies depending on neoadjuvant therapy:
1: neoadjuvant-ddAC/THP+adjuvant-H;
2: neoadjuvant-ddAC/THP+adjuvant-T-DM1;
3: neoadjuvant-THP+adjuvant-ddAC+T-DM1;
4: neoadjuvant-HP+adjuvant-ddAC/THP+T-DM1;
5: neoadjuvant-TCHP+adjuvant-T-DM1.

We estimated costs and quality-adjusted life years (QALYs) over a lifetime for each treatment strategy, and an incremental cost-effectiveness ratio (ICER), from a US healthcare payer perspective.

We found that, in a HER2-positive patient population, neoadjuvant THP followed by adjuvant ddAC and T-DM1 for residual disease and trastuzumab only for pCR is the most effective and least costly treatment regimen that produces clinical outcome similar to most expensive and more toxic (at the patient population level) treatment strategies.

MedicalResearch.com: What recommendations do you have for future research as a result of this study?

Response: Not all pre- and post-operative combinations that we examined in the study have been tested in clinical trials, for these clinical strategies we made assumptions about clinical outcomes based on extrapolations. There are clinical trials underway that test the outcome with some of these yet untested strategies.

MedicalResearch.com: Is there anything else you would like to add?

Response: These results inform what clinical trials will need to be conducted to safely select the most cost effective, least toxic therapy without compromising patient outcome , in a disease where many effective treatment strategies exist.

Any disclosures? Natalia Kunst has no financial conflicts to disclose. I received consulting fees and honoraria from Seattle Genetics, Pfizer, Astra Zeneca, Merck, Novartis, Bristol-Myers Squibb, Pfizer, Genentech, Eisai, Pieris, Immunomedics, Clovis, Syndax, H3Bio, Radius Health, and Daiichi. My institution receives clinical trial and research funding from Seattle Genetics, AstraZeneca, Merck, Pfizer and Bristol Myers Squibb for studies where I serve as the principal investigator.

Citation:

Kunst N, Wang S, Hood A, et al. Cost-Effectiveness of Neoadjuvant-Adjuvant Treatment Strategies for Women With ERBB2 (HER2)–Positive Breast Cancer. JAMA Netw Open. 2020;3(11):e2027074. doi:10.1001/jamanetworkopen.2020.27074

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