Shubham Pant, MD, associate medical director of the Clinical & Translational Research Center, associate professor in the Department of Gastrointestinal Medical Oncology at The University of Texas MD Anderson Cancer Center, discusses the role of genetic testing in pancreatic cancer.

Genetic testing has been a welcome addition to the pancreatic cancer armamentarium, says Pant.

Germline genetic testing can identify key inherited mutations within a patient’s blood, explains Pant. Conversely, somatic genetic testing identifies aberrations within the tumor.

Germline and somatic testing results can inform whether a patient is a candidate for targeted therapy, Pant says.

Currently, the National Comprehensive Cancer Network and the ASCO guidelines recommend that all patients with pancreatic cancer undergo germline testing to identify 

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Shubham Pant, MD, discusses the role of genetic testing in pancreatic cancer.  



Dr. Pant on the Role of Genetic Testing in Pancreatic Cancer 

Shubham Pant, MD, associate medical director of the Clinical & Translational Research Center, associate professor in the Department of Gastrointestinal Medical Oncology at The University of Texas MD Anderson Cancer Center, discusses targeting 

 mutations in advanced or metastatic solid tumors.

An ongoing, phase 1 first-in-human trial (NCT04111458) is evaluating the novel pan-KRAS inhibitor BI 1701963, which binds to son of sevenless homolog 1 (SOS1), alone and in combination with the MEK inhibitor trametinib (Mekinist) in patients with advanced 

 was thought to be an undruggable target, Pant explains. However, targeting 

 mutations are present in multiple tumor types including lung cancer, colorectal cancer, cholangiocarcinoma, and pancreatic cancer.

 phosphorylation and prevents activation of the 

 pathway. Ultimately, this may starve the tumor of its growth signal, explains Pant. Additionally, combining BI 1701963 with trametinib could block the RAS/RAF/MEK pathway to provide a more pronounced antitumor effect, concludes Pant. 

Shubham Pant, MD, discusses targeting KRAS mutations in advanced or metastatic solid tumors.  



Dr. Pant on Targeting KRAS Mutations in Metastatic Solid Tumors 

Shubham Pant, MD, associate medical director of the Clinical & Translational Research Center, associate professor, Department of Gastrointestinal Medical Oncology and Department of Investigational Cancer Therapeutics, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, discusses choosing therapy for the frontline and beyond in pancreatic cancer.

Treatment for patients with pancreatic cancer need to be selected on an individual level. Typically, the 2 frontline regimens are modified FOLFIRINOX or the combination of gemcitabine and nab-paclitaxel (Abraxane). FOLFIRINOX is typically used in more robust patients with a better performance status whereas gemcitabine/nab-paclitaxel is used in patients who have a performance status of 2.

Pancreatic cancer is a debilitating disease; often, patients cannot receive second-line therapy. The question of whether a patient is strong enough to receive second-line treatment must be considered carefully. Will the treatment improve the quantity or quality of their life? If yes, second-line therapy should be considered, concludes Pant.

Shubham Pant, MD, discusses choosing therapy for the frontline and beyond in pancreatic cancer.

Dr. Pant on Choosing Therapy for Frontline and Beyond in Pancreatic Cancer

Shubham Pant, MD, associate medical director of the Clinical & Translational Research Center, associate professor, Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, discusses exciting data with PARP inhibitors in pancreatic cancer.

Olaparib (Lynparza) was recently approved for use as maintenance therapy in patients with germline 

 mutations following 4 months of platinum-based therapy. The approval was based on data from the phase III POLO trial, which showed an improvement in progression-free survival and overall survival with olaparib versus placebo, says Pant.  

Investigators are actively pursuing other alterations within the DNA damage repair (DDR) pathway in order to expand the utility of PARP inhibitors to other patients. The DDR pathway encompasses several genes. There are some initial data on 

, which is a DDR gene. Other DDR genes might not be so affected by PARP, but trials are ongoing right now. Clinical trials are also evaluating 

, which is one of the other DDR genes in addition to ATR inhibitors, which target resistance mechanisms to PARP. These agents will be evaluated as monotherapy and in combination with other PARP agents, concludes Pant.

Shubham Pant, MD, discusses exciting data with PARP inhibitors in pancreatic cancer.

Dr. Pant on Exciting Data With PARP Inhibitors in Pancreatic Cancer

Shubham Pant, MD, associate medical director of the Clinical & Translational Research Center, associate professor, Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, discusses combination immunotherapies and upcoming developments in pancreatic cancer.

There is a lot of interest in immunotherapy in the field of oncology; however, this has been more of a challenge in pancreatic cancer, says Pant. However, combination immunotherapies, especially agents that target tumor microenvironments and create a less immune suppressive microenvironment, look promising.

A few different agents are in development to improve the performance status of these patients while they are getting chemotherapy. There are also ongoing trials that measure performance status while they are being treated with chemotherapy and if it improves while receiving active therapy or targeted therapy. These data are being tracked with Fitbits and other devices, concludes Pant.

Shubham Pant, MD, discusses combination immunotherapies and upcoming developments in pancreatic cancer.
 

Dr. Pant on Immunotherapy Combos and Upcoming Developments in Pancreatic Cancer

Shubham Pant, MD, associate medical director of the Clinical & Translational Research Center, associate professor, Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, discusses ongoing efforts in metastatic colorectal cancer (mCRC) and his hope for the future treatment landscape.

The future looks very promising. Pant notes that years ago, lung cancer was divided into non—small cell lung cancer, adenocarcinoma, squamous cell carcinoma, etc. Now, diagnoses are becoming more specific to 

The hope is to be able to stratify CRCs the same way. Right now, there are microsatellite instability-high, and 

-mutated cancers. Additionally, patients with 

 mutations need new therapies. KRAS inhibitors are in development. Combination approaches with translocations downstream of KRAS, such as RAS, RAF, MEK, ERK may be worth investigating.

Dr. Pant on the Future of mCRC Treatment

Shubham Pant, MD, associate professor, The University of Texas MD Anderson Cancer Center, discusses the third-line setting for patients with metastatic colorectal cancer (CRC).

According to Pant, there are not many options for patients with CRC in the third-line setting. Currently, regorafenib (Stivarga) and TAS-102 are the only options for this setting.

Next-generation sequencing is important to determine targets for treatment, explains Pant.

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Dr. Pant on the Third-Line Setting for Metastatic CRC

Shubham Pant, MD, associate professor, The University of Texas MD Anderson Cancer Center, discusses the current treatment landscape of colorectal cancer (CRC).

Patients with CRC need more options, says Pant. In a disease with a high varitey of mutations, treatments need to be developed in order to find the optimal therapy for each patient population.

Shubham Pant, MD, associate professor, The University of Texas MD Anderson Cancer Center, discusses the current treatment landscape of colorectal cancer.

Shubham Pant, MD