Pant Provides Insight on Key ASCO 2020 Data in Gastrointestinal Malignancies

Shubham Pant, MD

The 2020 ASCO Virtual Scientific Program provided a wealth of practice-changing information in the field of gastrointestinal (GI) malignancies, explained Shubham Pant, MD.

For example, the phase 3 MK-3475/KEYNOTE-177 trial demonstrated encouraging results with the checkpoint inhibitor pembrolizumab (Keytruda) when compared with standard-of-care chemotherapy in patients with microsatellite instability–high (MSI-H) or mismatch repair deficient stage IV colorectal cancer (CRC).

Additionally, the phase 2 ESPAC-5F and SWOG S1505 trials shed light on the role of neoadjuvant treatment in borderline resectable and resectable pancreatic cancer, respectively.

In an interview with OncLive, Pant, an associate professor in the Department of Investigational Cancer Therapeutics and Gastrointestinal Medical Oncology, and associate director of the Department of Sheihk Ahmed Center for Early Phase Drug Development of Pancreatic Cancer Research in the Division of Cancer Medicine at The University of Texas MD Anderson Cancer Center, discussed key data that emerged in the GI oncology space from the 2020 ASCO Virtual Scientific Program.

OncLive: Could you discuss the ESPAC-5F trial and explain its clinical impact on patients with pancreatic cancer?

Pant: ESPAC-5F is an interesting trial in patients with borderline resectable pancreatic cancer. It was a 4-arm, prospective, multicenter, phase 2 clinical trial that randomized patients to receive surgery up front or neoadjuvant chemotherapy. Patients could have received gemcitabine/capecitabine (Xeloda), FOLFIRINOX [leucovorin, fluorouracil (5-FU), irinotecan, oxaliplatin] or chemoradiation. Borderline resectable pancreatic cancer means that the cancer touches some vessels without incasing the vessels.

Patients with borderline resectable pancreatic cancer did much better with neoadjuvant therapy. The 1-year survival rate with up-front surgery was around 40% compared with 77% with neoadjuvant therapy. That is a great result. The numbers are small; 32 patients underwent up-front surgery, 20 received gemcitabine/capecitabine, 20 received FOLFIRINOX, and 16 received chemoradiation.

Pancreatic cancer is a systemic disease, and we need to kill the micrometastases before patients go in for surgery. Neoadjuvant therapy should be [given] to most, if not all, patients who [present] with borderline resectable pancreatic cancer. That is what we have been doing in the clinic; [the trial has] been a great validation of the strategy.

Switching gears to the SWOG S1505 study, what were the important takeaways from that trial?

The phase 2 SWOG S1505 study enrolled patients with resectable pancreatic cancer and randomized them to gemcitabine and nab-paclitaxel (Abraxane) or modified FOLFIRINOX. Patients received half of [their treatment] before surgery.

The take-home message from that study is that we still do not know which regimen to use in the frontline setting as there was no statistical difference between treatments. We know that both regimens can be used in the neoadjuvant setting. Interestingly, if we look at the adjuvant data, there was a positive trial of FOLFIRINOX versus gemcitabine. The trial of gemcitabine plus nab-paclitaxel versus gemcitabine alone was not positive.

We feel like the majority of patients should receive some kind of neoadjuvant therapy. Choosing between FOLFIRINOX or gemcitabine/nab-paclitaxel [could be based on] individual patient characteristics.

What are the next steps regarding these data? Based on these data, what is the role of neoadjuvant therapy in pancreatic cancer?

Essentially, the next steps would be to look at the data again when it matures more. Additionally, perhaps future trials could look at biomarkers. For example, we know that patients who have BRCA1/2 germline mutations tend to do better with platinum-based therapy. In those patients who have [BRCA mutations], perhaps starting them on platinum-based regimens like modified FOLFIRINOX or a cisplatin-based therapy [is optimal].

A presentation at the 2020 Gastrointestinal Cancers Symposium in metastatic pancreatic cancer with capecitabine and cisplatin showed encouraging response rates. In patients who are BRCA1/2 positive, a platinum-based neoadjuvant treatment approach is appropriate.

Other than that, we don’t know. Hopefully we’ll identify more biomarkers that will allow us to focus the right treatment on the right patient in the future.

Were there any other key trials that are important to highlight?

The last trial that everybody has talked about is the phase 3 MK-3475/KEYNOTE-177 trial. This study randomized patients with MSI-H stage IV CRC to pembrolizumab or [standard-of-care] chemotherapy. The bottom line is that these findings were practice changing for our patients who have MSI-H stage IV CRC.

We should be doing MSI testing for patients with any stage of CRC. [In KEYNOTE-177, we saw] that the disease-free survival curves were far apart, meaning that patients who have MSI-H CRC can derived a lot of benefit with a checkpoint inhibitor, specifically pembrolizumab in this case, compared with chemotherapy. This is exciting because it can spare patients the toxicities of chemotherapy in the frontline setting.