COMMENTARY

Best of the 2017 ASCO Live Blog: Breast, Lung, Colon and Prostate Cancer

David L. Graham, MD; Kevin Kalinsky, MD, MS; Alok A. Khorana, MD; H. Jack West, MD

Disclosures

June 13, 2017

Throughout ASCO 2017, experts across a wide range of tumor types and research interests contributed their perspectives on the meeting to Medscape's ASCO 2017 Live Blog. Here is a compilation of the most important live blog posts from the meeting, including perspectives on a number of studies that will probably change practice immediately.

Breast Cancer

Kevin Kalinsky, MD, MS: An important topic in breast cancer at ASCO this year was poly ADP ribose polymerase (PARP) inhibition. There have been significant ups and downs in the PARP story before ASCO 2017. PARP inhibitors and synthetic lethality generated a great deal of clinical enthusiasm at ASCO meetings dating back to 2009, with the reporting of the phase 2 study of iniparib in metastatic triple-negative breast cancer. This study included patients with and without germline BRCA mutations.

Unfortunately, the subsequent randomized phase 3 trial was negative. Of note, investigators have subsequently argued that iniparib was not a true PARP inhibitor.

Since then, clinical data with PARP inhibitors have been mixed. For instance, veliparib/carboplatin graduated with a high probability of success from the I-SPY study and was published in New England Journal of Medicine. On the other side, adding veliparib to chemotherapy did not lead to a statistically significant improvement in progression-free or overall survival in a phase 2 trial of patients with metastatic breast cancer who had germline BRCA1/2 mutations, as reported at the 2016 San Antonio Breast Cancer Symposium.[1]

At the ASCO 2017 plenary session, the results of the OlympiAD trial were presented (also published online in the New England Journal of Medicine). This phase 3 trial compared olaparib monotherapy 300 mg twice daily versus physician choice chemotherapy in a 2:1 fashion in patients with germline BRCA mutations and HER2-negative metastatic breast cancer. Of note, if prior platinum had been given, no evidence of progression during treatment in the advanced setting was allowed with the platinum, and at least 12 months must have passed since platinum therapy.

With a median follow-up of approximately 14 months, there was a significant improvement in progression-free survival with olaparib versus chemotherapy (7.0 months vs 4.2 months), as well as a prespecified improvement in time to second progression or death (13.2 months vs 9.3 months).

So, why the differences with PARP studies?

First, not all PARP inhibitors are created the same. For instance, there are differences in biochemical trapping of PARP1 by the various PARP inhibitors, including olaparib, rucaparib, niraparib, veliparib, and talazoparib.

Second, the designs vary among the studies—most notably, whether patients have previously received or are concomitantly being administered a platinum. This has been demonstrated in other trials presented at this meeting. In an exploratory analysis of the final reporting of the ABRAZO trial—a phase 2 study of talazoparib following platinum or multiple cytotoxic regimens in metastatic BRCA1/BRCA2 mutations—among those who received talazoparib after platinum-based therapy, anticancer activity appeared to be greater in patients who were further away from receiving platinum therapy.

Also, in a phase 3 neoadjuvant trial presented at the ASCO 2017 poster discussion, there was no statistical difference in pathologic complete response when veliparib was added to neoadjuvant carboplatin plus paclitaxel followed by doxorubicin and cyclophosphamide in high-risk triple-negative breast cancer. Thus, timing of other DNA-damaging agents, including platinum, is an important consideration.

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