Syma Iqbal, MD, assistant professor, Division of Oncology, assistant program director, Fellowship Program, Department of Oncology, educational officer, Division of Oncology, co-director, Liver Cancer Program, Norris Comprehensive Cancer Center, Keck Medicine of USC, discusses determining whether to start with regorafenib (Stivarga) or trifluridine/tipiracil (TAS-102; Lonsurf) in metastatic colorectal cancer (mCRC). 

Sequencing of therapies for patients with mCRC remains a challenging decision that requires more attention, Iqbal explains. This is particularly true in the later-line settings where patients can receive regorafenib or TAS-102.

Data strongly support the use of appropriately dosed regorafenib before TAS-102 for patients with mCRC who have good performance status and adequate albumin, Iqbal says. Moreover, patients with refractory mCRC who receive regorafenib first tend to have better outcomes compared with patients who start TAS-102 first, Iqbal concludes.

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Syma Iqbal, MD, discusses determining whether to start with regorafenib (Stivarga) or trifluridine/tipiracil (TAS-102; Lonsurf) in metastatic colorectal cancer (mCRC).  



Dr. Iqbal on Determining Whether to Start With Regorafenib or TAS-102 in mCRC 

Syma Iqbal, MD, assistant professor, Division of Oncology, assistant program director, Fellowship Program, Department of Oncology, educational officer, Division of Oncology, co-director, Liver Cancer Program, Norris Comprehensive Cancer Center, Keck Medicine of USC, discusses the emergence of checkpoint inhibitors in upper gastrointestinal (GI) cancers.

After a period of negative trials, several positive studies have read out that confirm the role for checkpoint inhibitors in the frontline treatment of patients with advanced upper GI tumors irrespective of HER2 status, Iqbal says. Additionally, the checkpoint inhibitor nivolumab (Opdivo) demonstrated efficacy as adjuvant therapy for patients with completely resected esophageal or gastroesophageal junction cancer with residual pathologic disease who received neoadjuvant chemoradiotherapy. Nivolumab induced a disease-free survival of 22.4 months vs 11 months with placebo. 

Although the integration of checkpoint inhibitors in upper GI tumors represents a significant advancement, the field must adapt ongoing and developing clinical trials amid the emergence of this new standard of care, Iqbal concludes.

Syma Iqbal, MD, discusses the emergence of checkpoint inhibitors in upper gastrointestinal cancers.  



Dr. Iqbal on the Emergence of Checkpoint Inhibitors in Upper GI Cancers 

Syma Iqbal, MD, an associate professor of clinical medicine at the Keck School of Medicine, University of Southern California, discusses the need to discover more reliable biomarkers in gastric cancer.

To date, the only consistent biomarker for gastric cancer has been HER2, Iqbal says. Patients with HER2-positive disease benefit from HER2 suppression in the frontline setting with targeted agents such as trastuzumab (Herceptin). Other than HER2, the only other biomarker that has shown potential in gastric cancer has been PD-L1, which is thought to be predictive of immunotherapy response.

PD-L1 expression has been particularly effective in other diseases like lung cancer and melanoma, but there are still unanswered questions regarding its use in gastric cancer. Therefore, Iqbal says she is unsure if she’s ready to consider PD-L1 as a biomarker in routine clinical practice.

Iqbal adds that even the HER2 story has had its caveats in this space. While targeted therapy works in the frontline setting, it has yet to show any benefit for second-line treatment.

Syma Iqbal, MD, associate professor of clinical medicine, Keck School of Medicine, University of Southern California, discusses the treatment of patients with HER2-driven gastric cancer.

Dr. Iqbal on HER2-Driven Gastric Cancer

Syma Iqbal, MD, associate professor of clinical medicine, Keck School of Medicine, University of Southern California, discusses the impact of peptide receptor radionuclide therapy (PRRT) on the treatment of patients with neuroendocrine tumors (NETs).

PRRT has been the biggest advance in the treatment paradigm, says Iqbal. The randomized NETTER-1 trial compared Lutathera (lutetium Lu 177 dotatate) with octreotide (Sandostatin). Results indicated a 0.21 HR for progression-free survival which is unprecedented in the field. The therapy showed a significant benefit for patients and was well tolerated, says Iqbal. Now that it is FDA approved and has demonstrated a long-term benefit, it will be something that is used often in practice, adds Iqbal.

Now that physicians have multiple therapeutic options, they need a way of predicting response to therapy. Moreover, immunotherapy may enter the field in both in low- and high-grade tumors, though there is still a lot of research to do, Iqbal concludes.

Dr. Iqbal on the Biggest Advance in the Treatment of Neuroendocrine Tumors

Syma Iqbal, MD, associate professor of clinical medicine, Keck School of Medicine, University of Southern California, discusses second- and third-line therapies in gastric cancer.

Physicians have a lot of options in the second-line setting, following the introduction of targeted therapies such as ramucirumab (Cyramza), says Iqbal. The VEGFR-2 inhibitor was FDA approved in 2014 as a treatment for patients with unresectable gastric cancer or gastroesophageal junction (GEJ) adenocarcinoma following fluoropyrimidine- or platinum-containing therapy. In 2017, the agent was tested in combination with cisplatin and capecitabine or 5-FU (5-fluorouracil) in the frontline setting but failed to improve overall survival in patients with HER2-negative metastatic gastric or GEJ adenocarcinoma.

Moreover, immunotherapy has made an impact in the field. Currently, pembrolizumab (Keytruda) is FDA approved in the third-line setting for patients who are PD—L1 positive. These patients have about a 15% response rate, adds Iqbal. Durability has been seen in some patients, though not commonly. The goal now, says Iqbal, is to move immunotherapy into the first- and second-line settings.

Dr. Iqbal on Second- and Third-Line Therapies in Gastric Cancer

Syma Iqbal, MD, associate professor of clinical medicine, Keck School of Medicine, University of Southern California, discusses treatment options for patients with neuroendocrine tumors (NETs).

NETs used to be a very rare malignancy, but the incidence has been increasing and physicians are seeing more cases, says Iqbal. Luckily, physicians have more treatment options now than before. The introduction of somatostatin analogues and peptide receptor radionucleotide therapy (PRRT) have transformed the field, explains Iqbal. In January 2018, Lutathera (lutetium Lu 177 dotate) was FDA approved for patients with somatostatin receptor—positive gastroenteropancreatic NETs.

Moreover, clinical trials have demonstrated the activity of targeted therapies, mTOR inhibitors, and VEGF inhibitors, but physicians do not yet have a clear picture of how to sequence these therapies, says Iqbal. A patient who has well-differentiated low-grade disease is going to live a very long time, but they are probably going to go progress through multiple lines of treatment, says Iqbal, further underscoring the need to determine the best sequence of therapies.

Syma Iqbal, MD

Articles

Dr. Iqbal on Determining Whether to Start With Regorafenib or TAS-102 in mCRC

Dr. Iqbal on the Emergence of Checkpoint Inhibitors in Upper GI Cancers

Dr. Iqbal on HER2-Driven Gastric Cancer

Dr. Iqbal on the Biggest Advance in the Treatment of Neuroendocrine Tumors

Dr. Iqbal on Second- and Third-Line Therapies in Gastric Cancer

Dr. Iqbal on Treatment Options for Patients With Neuroendocrine Tumors