Tanios Bekaii -Saab, MD

With significant advances in precision medicine in oncology, only an exceedingly small percentage of pancreatic ductal adenocarcinoma (PDAC) cases benefit from targeted therapy based on tumor biomarker selection. Over the last 2 years, emerging agents with novel molecular targets continue to show promising clinical activity.

As our knowledge of the tumor genomic landscape broadens, the ability to test for actionable genetic variants has become commonplace in our daily practice. Presently, the National Comprehensive Cancer Network (NCCN) recommends inherited (germline) mutation testing to all patients with PDAC, and somatic molecular profiling in all patients with locally advanced or metastatic disease.

With precision medicine changing the therapeutic paradigm for most solid tumors, its benefit applies to a dismally small percentage of advanced PDAC. Since the last American Society of Clinical Oncology (ASCO) update on metastatic PDAC in 2020, emerging trials with novel targeted agents continue to demonstrate encouraging results.

 gene is quasi-ubiquitously mutated in over 90% of PDAC tumors. Within this gene, an activating G12D substitution occurs most frequently in 40% of cases, followed by G12V (30%), G12R (up to 20%), and G12C (1%-3%).

 Once considered “non-druggable”, KRAS gene inhibition is making its way into clinical trials and to the clinic. With a focus on small deactivating molecules and adoptive cell therapy the number of PDAC tumors eligible for targetable therapy may exponentially grow soon.

Adagrasib (MRTX849) and sotorasib (Lumakras) are 2 oral small molecules that inhibit specifically and irreversibly 

 G12C. The efficacy of adagrasib is being evaluated by the KRYSTAL-1 trial (NCT03785249), a multicohort phase 1/2 study enrolling patients with 

Within the gastrointestinal tumor subgroup, a preliminary analysis included 12 individuals with PDAC who had received a median of 3 prior lines of therapy. Clinical activity was evaluable in 10 patients, 5 of which achieved a partial response (PR), and the remaining 5 patients attained stable disease (SD). Median progression-free survival (PFS) was 6.6 months (95% CI, 1.0-9.7) in the pancreas-specific cohort.

In another combined phase 1/2 trial (NCT03600883) with 38 patients with PDAC, sotorasib monotherapy achieved a PR in 8 (21%) patients and a SD in 24 (63.1%) patients. Median PFS and overall survival (OS) were 3.98 (95% CI, 2.8-5.6) and 6.9 months (95% CI, 4.9-9.1), respectively.

Gastrointestinal toxicities and fatigue were reported with both agents, but adagrasib also caused QTc prolongation, whereas the sotorasib study observed cases of hepatotoxicity, pleural effusion, and pulmonary embolism.5,6 Of notable significance, the identification of MRTX1133, a specific KRAS G12D inhibitor, may significantly expand the applicability of KRAS inhibition in PDAC tumors.

 The safety and efficacy of this treatment remain to be examined in ongoing clinical trials.

Adoptive cell therapy has also been employed to target specific 

 mutations in patients with PDAC. In a recent case report, autologously administered 

 G12D–reactive tumor-infiltrating lymphocytes was given to a 71-year-old patient with recurrent PDAC. Conditioning regimen to support in vivo T cell expansion included tocilizumab and cyclophosphamide prior to cell infusion, and high-dose interleukin-2 after infusion.

The patient then had a PR, with a 62% reduction of metastases at 1 month and a 72% reduction at 6 months. In the same study, the authors also reported the outcome of a second patient treated with the same product, albeit with a different manufacturing process and preconditioning regimen. This patient experienced grade 3 cytokine release syndrome and a grade 2 immune effector cell-associated neurotoxicity syndrome. However, despite persistently high levels of T cell in the peripheral blood, the patient experienced disease progression and passed at 6 months after cell infusion.

Approximately 6% to 9% of PDAC tumors harbor a germline pathogenic and likely pathogenic variant (P/LPV) of 

 Loss of BRCA1/2 function leads to deficient repair of DNA double-strand break in tumor cells. As a result, these cells experience sensitized response to DNA-damaging treatments with platinum and PARP inhibitors.

In 2019, the FDA approved olaparib (Lynparza), an oral PARP inhibitor, as maintenance therapy in patients with metastatic germline 

-mutated PDAC who had a platinum-sensitive disease, which was defined as no disease progression after 16 weeks of first-line platinum-based therapy.

This approval was based on clinical benefits seen in the preliminary results from the POLO study (NCT02184195). In this double-blind randomized trial participants had platinum-sensitive stage IV PDAC and olaparib (Lynparza) showed a superior PFS compared with placebo with a median PFS of 7.4 months (95% CI, 4.1-11.0) and 3.8 months (95% CI, 3.5-4.9), respectively (HR, 0.53; 95% CI, 0.35-0.81; 

Final OS data had a 70.1% data maturity and was published in July 2022. There was no significant difference in OS between olaparib and placebo with a median OS of 19.0 and 19.2 months, respectively (HR, 0.83; 95% CI, 0.56-1.22; 

 Nevertheless, olaparib exhibited an adequate safety profile and was associated with significantly longer median time to first subsequent cancer therapy or death (HR, 0.44; 95% CI, 0.30-0.66; 

 < .0001). Moreover, the estimated 3-year survival in the olaparib arm was 33.9% compared with the placebo group at 17.8%.

Beyond olaparib, the efficacy of continuous rucaparib (Rubraca) was examined in a recent single-arm phase 2 study (NCT03140670).

As key differences to the POLO trial, inclusion criteria in this study incorporated participants with locally advanced PDAC tumors, and those with germline 

 P/PLVs, as well as germline and somatic 

 variants. In 42 patients with evaluable disease, median PFS and OS were 13.1 and 23.5 months, respectively. Overall, an objective response was seen in 15 (35.7%) patients. Three responders had a germline 

 alteration. None of the 7 patients with a germline 

 variant responded. Median duration of response was 17.3 months.

A recent phase 1b/2 study also explored maintenance immunotherapy plus PARP inhibition in platinum-sensitive PDAC tumors. Participants with advanced disease were randomized to receive niraparib with either nivolumab (Opdivo; n = 46) or ipilimumab (Yervoy; n = 45). The primary end points included PFS at 6 months, which was 20.6% (95% CI, 8.3%-32.9%) in the nivolumab doublet arm, and 59.6% (95% CI, 44.3%-74.%9) in the ipilimumab doublet group.

 Grade 3 or higher treatment-related adverse events (AEs) occurred in 22% and 50% of the participants in nivolumab and ipilimumab arms, respectively.

The most common severe AEs were hypertension, anemia, and thrombocytopenia. Of note, as allowed by the study protocol, over 80% of participants in both groups did not harbor an DNA damage repair pathway variant. Moreover, the authors did not report tumor status of microsatellite instability-high (MSI-H) and mismatch repair deficiency (dMMR), which are positive response predictors for immunotherapy.

In 2017, the FDA approved pembrolizumab as the first tissue-agnostic therapy for all tumors with MSI-H and/or dMMR.

 Two additional agents, entrectinib (Rozlytrek) and larotrectinib (Vitrakvi), received approvals for advanced solid tumors with 

 fusion regardless of the primary tumor histology.

 Presently, these agents are indicated for second-line treatment of patients with metastatic PDAC tumors. Nevertheless, the clinical benefit of these treatments is limited by the small portion of patients with qualifying molecular alterations (<1% of patients have an MSI-H/dMMR tumor, and <0.5% with a 

Two additional regimens, selpercatinib (Retevmo) and dabrafenib (Tafinlar)/trametinib (Mekinist), have received tumor-agnostic regulatory approval, albeit their use in PDAC has yet to be endorsed by the NCCN or ASCO guidelines.

Selpercatinib is an orally available highly selective RET kinase inhibitor approved for the treatment of locally advanced or metastatic solid tumors with a 

 gene amplifications and mutations occur in up to 3.7% of tumors, whereas 

 fusion are detected in less than 1% of cases.

 In LIBRETTO-001 (NCT03157128), a phase 1/2, open-label, basket trial, the authors included a tumor-agnostic sub-cohort with 45 patients with 

 fusion–positive solid tumors. Eleven out of 12 patients with PDAC had evaluable response, and of these 6 achieved a PR with an overall response rate 54.5% (95% CI, 23.4-83.3).

At data cutoff, median duration of response was not reached; 1 patient had remained on oral selpercatinib for over 40 months. The most common grade 3 or higher AEs attributed to selpercatinib were hypertension (22%), elevated alanine aminotransferase (16%), and elevated aspartate aminotransferase (13%). Dose reduction and then discontinuation were warranted in 14 (31%) and 1 (2%) of patients, respectively.

 mutation occurs in approximately 3% of all PDAC tumors, being 

V600E the most common alteration. Combined BRAF-MEKinhibition with respective dabrafenib and trametinib received FDA approval for all 

 This histology-agnostic indication in adults was supported by clinical benefit observed in 2 clinical trials, the phase 2 ROAR (Rare Oncology Agnostic Research) basket study and the NCI-MATCH (NCT02465060) study.

 Notably, from all 131 patients enrolled in both trials, only the latter included 3 patients with 

V600E-mutant PDAC tumors. Of these, 2 had evaluable disease including 1 case of SD and 1 had disease progression. Their response duration was not reported.

mutatedPDAC remains anecdotal. In the KYT registry, 1 patient with 

mutatedPDAC received dabrafenib/trametinib as second-line treatment and showed sustained response for eleven months. One other patient with 

 fusion remained less than one month on fourth-line dabrafenib/trametinib due to intolerance.

Prospectively, the single-arm phase 2 BrafPanc trial (NCT04390243) aims to examine the efficacy of encorafenib/binimetinib in locally advanced and metastatic 

V600E-mutant PDAC tumors, and the study is in active recruitment and is estimated to complete in December 2024.

Sacituzumab govitecan (Trodelvy), an antibody-drug conjugate targeting to trop-2, is currently approved for patients with advanced urothelial carcinoma and breast cancer.

 In the phase 1/2 IMMU-132-01 (NCT01631552) basket trial with patients with recurrent metastatic epithelial tumors; 16 patients had metastatic PDAC at enrollment. At a median follow-up of 9 months, 7 of these patients attained an SD, but the duration of response was not reached.

 In the overall safety population (n = 495), grade 3/4 neutropenia occurred in 42% of the patients, while 5% experienced febrile neutropenia, but 1 case of treatment-related death was reported due to aspiration pneumonia.

In a Chinese randomized trial with patients with locally advanced or metastatic PDAC and a wild-type 

, nimotuzumab, anti-EGFR humanized monoclonal antibody, combined gemcitabine was compared with gemcitabine or placebo. Although the ORR between the 2 groups were not statistically significant, the nimotuzumab regimen showed superior median OS compared with control at 10.9 vs 8.5 months, respectively (HR, 0.50; 95% CI, 0.06-0.94, 

 = .025). Subgroup analyses revealed additional OS benefit in patients who did not have a surgical history at 15.8 vs 6.0 months (HR, 0.40; 95% CI, 0.19-0.84) and those who did not require treatment for biliary obstruction at 11.9 vs 8.5 months (HR, 0.54; 95% CI, 0.33-0.88, 

 In the nimotuzumab arm, grade 3 AE included neutropenia (11.1%) and thrombocytopenia (6.7%), but no grade 4 AEs were reported.

Presently, cytotoxic therapy remains the foundation for the treatment of patients with PDAC tumors. However, emerging targeted therapies continue to show clinically meaningful benefit in a growing subset of PDAC tumors. Moreover, the number of trials based on PDAC tumor biomarker selection is experiencing an exponential growth, therefore, it is imperative to universally test for inherited and somatic alterations in patients diagnosed with PDAC.

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6. Bekaii-Saab T.S., Spira A, Yaeger R, et al. KRYSTAL-1: Updated activity and safety of adagrasib (MRTX849) in patients (Pts) with unresectable or metastatic pancreatic cancer (PDAC) and other gastrointestinal (GI) tumors harboring a KRASG12C mutation. Presented at: 2022 ASCO Gastrointestinal Cancers Symposium. Accessed: November 29, 2022. https://bit.ly/3gNSDNz

7. Strickler JH, Satake H, Hollebecque A, et al., First data for sotorasib in patients with pancreatic cancer with KRAS p.G12C mutation: A phase I/II study evaluating efficacy and safety. J Clin Oncol. 2022 Oct20;40(36):360490-360490. doi:10.1200/JCO.2022.40.36_suppl.360490

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13. O'Reilly EM, Lee JW, Zalupski M, et al. Randomized, Multicenter, Phase II Trial of Gemcitabine and Cisplatin With or Without Veliparib in Patients With Pancreas Adenocarcinoma and a Germline BRCA/PALB2 Mutation. J Clin Oncol. 2020 May 1;38(13):1378-1388. doi:10.1200/JCO.19.02931

14. Golan T, Hammel P, Reni M, et al. Maintenance Olaparib for Germline BRCA-Mutated Metastatic Pancreatic Cancer. N Engl J Med. 2019 Jul 25;381(4):317-327. doi:10.1056/NEJMoa1903387

15. Brown TJ, Reiss KA. PARP Inhibitors in Pancreatic Cancer. Cancer J. 2021 Nov-Dec 01;27(6):465-475. doi:10.1097/PPO.0000000000000554

16. Kindler HL, Hammel P, Reni M, et al. Overall Survival Results From the POLO Trial: A Phase III Study of Active Maintenance Olaparib Versus Placebo for Germline BRCA-Mutated Metastatic Pancreatic Cancer. J Clin Oncol. 2022 Dec 1;40(34):3929-3939. doi:10.1200/JCO.21.01604

17. Reiss KA, Mick R, O'Hara MH, et al. Phase II Study of Maintenance Rucaparib in Patients With Platinum-Sensitive Advanced Pancreatic Cancer and a Pathogenic Germline or Somatic Variant in BRCA1, BRCA2, or PALB2. J Clin Oncol. 2021 Aug 1;39(22):2497-2505. doi:10.1200/JCO.21.00003

18. FDA grants accelerated approval to pembrolizumab for first tissue/site agnostic indication. FDA. 2017 May 30, 2017. https://bit.ly/2lDQSG0

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29. FDA grants accelerated approval to sacituzumab govitecan for advanced urothelial cancer. April 13, 2021. Accessed: November 29, 2022. https://bit.ly/3gQ6HpK

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Articles

The landscape for patients with pancreatic ductal adenocarcinoma has shifted due to novel targeted therapies that are opening new options for patients. 

Pancreatic Cancer Awareness Month: Novel Targeted Therapy in PDAC

Tanios S. Bekaii-Saab, MD, FACP, medical oncologist, medical director, Cancer Clinical Research Office, vice chair and section chief, Medical Oncology, Department of Internal Medicine, Mayo Clinic, discusses the unmet needs that are hoped to be filled by the phase 1/2 KRYSTAL-1 study (NCT03785249).

To be enrolled in the KRYSTAL-1 study, patients need to have a solid tumor with a 

 G12C mutation and unresectable or metastatic non-small cell lung cancer which progressed on or after treatment with a PD-1/PD-L1 inhibitor in combination with or following chemotherapy.

In part 1 of the study, the dose escalation of adagrasib (MRTX849) was reviewed, determining the maximum-tolerated dose to be 600 mg twice a day. Adagrasib at this dosage demonstrated a clinical benefit rate of 96% in the phase 1/1b trial and progressed to be the recommended phase 2 dose.

Because adagrasib showed promising clinical activity in this patient population, Bekaii-Saab hopes this study will help to fill some of the unmet needs that continue to exist in this space.

 KRYSTAL-1 is a study that's built as a phase 1, phase 1B and phase 2 study. The key criteria for entry on the study is essentially to have a 

 G12C mutation. Phase 1 was essentially dose escalation that primarily looked at trying to determine the maximum tolerated dose, 600 mg twice a day. That ultimately went into expansion and included some rational combinations. Phase 2 was monotherapy and combination. Phase 1B for example, had an added grasp for all solid tumors and for brain metastases, since it has that CNS penetration. They looked at lung cancers, both treatment naive and those that were exposed to prior 

 In colon cancer, these G12C inhibitors don't appear to have much activity on their own. That is because of a feedback loop mechanism that essentially creates that adaptive resistance and activates 

. In colon cancer, most of the follow through development was with adagrasib and cetuximab (Erbitux), which is what's being developed right now in a large study called KRYSTAL-10, a phase 3 randomized study looking specifically at adagrasib plus cetuximab plus chemotherapy in second-line colon cancer.

In pancreas cancer, they expanded from a single agent which is still ongoing but also to look at cetuximab plus. The phase 2 had a single agent in colon cancer plus cetuximab in colon cancer, then pancreas cancer plus cetuximab. The data I presented was on the other solid tumor basket. At the time, we presented with 42 patients with adagrasib, a single agent, and then there are lung cancer lung cancer cohorts, both single agents and one that includes the 

 mutations. There’s quite a bit of data that has been presented prior to the presentation I did at ASCO GI that included showing activity in lung cancer, colon cancer, the few patients with pancreas, ovarian, endometrial, phalangeal, you name it. Every cancer where this agent has been looked at, as long as they harbor the 

 G12C mutation, there has been evidence of activity.

Videos

Tanios S. Bekaii-Saab, MD, FACP, discusses the unmet needs that are hoped to be filled by the phase 1/2 KRYSTAL-1 study.

KRYSTAL-1 May Fill Unmet Needs in KRAS G12C mutated GI Cancers

: Which factors affect the treatment of patients with colorectal cancer (CRC)? Which tests do you usually order in this setting?

BEKAII-SAAB: The patient’s characteristics and age are important; whether they had prior adjuvant therapy; comorbidities; tumor burden. Is this a disease that you want to hit hard? Is this potentially resectable? It seems next-generation sequencing [is being done quite] liberally, but if you are limited by your choices, the first 4 [markers] you want on hand would be 

, microsatellite instability [MSI] high, and then HER2 amplifications. HER2 amplifications not only lead to HER2-targeted therapies at some point but also help eliminate the need for EGFR inhibitors, because 

amplifications predict for lack of efficacy of EGFR inhibitors. And, of course, patient preference [is also an important factor].

Which therapies do the National Comprehensive Cancer Network (NCCN) guidelines suggest?

The NCCN guidelines are a hodgepodge of [choices], and they really don’t limit you to 1 or 2 options. Pembrolizumab [Keytruda] is a first-line option for patients with MSI-high CRC given the results from KEYNOTE-177 [NCT02563002] that were presented at the American Society of Clinical Oncology [plenary session] and are now published as a paper in the 

What is your impression of this patient’s case so far?

It’s reasonable to do FOLFOX, although the preference would be for FOLFIRI [folinic acid, fluorouracil, and irinotecan]. Twenty percent to 30% will have a response, regardless of prior exposure, to oxaliplatin, as long as it’s been a while.

The patient started developing peripheral neuropathy—not too bad, though. But at this point, the patient has had enough oxaliplatin to consider the response as plateaued.

An old paper suggests that it doesn’t matter how you sequence FOLFOX or FOLFIRI; you get about the same benefit, and the same is true today.

What are the data supporting the use of regorafenib (Stivarga) for patients with CRC?

The phase 3 CORRECT trial [NCT01103323] was the initial study with regorafenib, which showed a median overall survival [OS] of 6.4 months [with regorafenib] versus 5.0 months for placebo [HR, 0.77; 95% CI, 0.64-0.94; 

 But the toxicities came early. In the first 2 weeks, you start seeing hand-foot syndrome, fatigue, and other toxicities like hypertension, which have limited the use. There have been a number of attempts to clinically [decrease these toxicities]; physicians have been using regorafenib every way they [could], starting with 80 mg or 120 mg, [to get to] 160 mg. There were not many data to help us understand a strategy to optimize the dose.

Some refer to [the ReDOS] study [NCT02368886] that we published in 

 in 2019, and it was a large phase 2 randomized study looking at regorafenib.

 It was [increased] from 80 mg to 120 mg to 160 mg on a weekly basis, weeks 1, 2, and 3, and then with a week off versus 160 mg [daily for] 3 weeks on, 1 week off. The study’s primary end point was a composite end point of efficacy and tolerability. In other words, patients were accounted for if they essentially got to cycle 3 and then continued beyond cycle 3. It means that they tolerated the drug [well] enough and they responded well enough.

The primary end point of the study was positive, where the dose-escalation strategy was superior to the standard-dose strategy. The OS was surprising; this was a secondary end point, [and we] thought survival wasn’t going to look much better, but it did look better with the dose-escalation strategy versus the standard dose, at 10 months versus 6 months, [respectively; HR, 0.72; 95% CI, 0.47-1.10; 

This changed the NCCN guidelines, and [regorafenib was added] as an option. Not only has this become the preferred way to give regorafenib in the United States, but it has become adopted across most of the world.

Can you discuss the trials for TAS-102 (trifluridine/tipiracil; Lonsurf)?

TAS-102 came on the heels of the RECOURSE study [NCT01607957] randomizing patients to TAS-102 versus placebo, with a primary end point of OS.

 There were similar trends with RECOURSE OS and progression-free survival [PFS] to what we’ve seen with regorafenib. There has never been a formal head-to-head comparison, but the results look similar.

The toxicity profile was a bit different. You see mostly neutropenia. In fact, 4% of patients [on regorafenib] had febrile neutropenia. I had a couple of patients over the past few years who ended up with febrile neutropenia and were admitted to the hospital. We often think about oral medications as less toxic from that standpoint.

 This study essentially was an indirect comparison, a network meta-analysis. What we found, essentially, is what you would expect. If you look at regorafenib 160 mg versus TAS-102, it’s pretty much a wash. OS and PFS hazard ratios were very similar, not much difference between the 2 [OS HR, 1.00; PFS HR, 0.93]. We also took the regorafenib schedule, the 80-plus mg, and compared it indirectly with historical best supportive care to confirm that it will maintain that value. The hazard ratios are impressive with this [OS HR, 0.44; PFS HR, 0.37]. When we compared regorafenib 80-plus mg with 160 mg from all randomized studies, regorafenib 80-plus mg maintained its advantage versus regorafenib 160 [OS HR, 0.65; PFS HR, 0.89]. We compared 80-plus mg with TAS-102—the 

 values were not positive, so it was just a numerical improvement with the 80-plus mg. Our conclusion was that there is definitely a trend for improved survival when you look at regorafenib 80 mg, 120 mg, and 160 mg versus regorafenib 160 mg or TAS-102, to be confirmed in larger trials, if that ever happens.

1. André T, Shiu KK, Kim TW, et al; KEYNOTE-177 Investigators. Pembrolizumab in microsatellite-instability-high advanced colorectal cancer. N Engl J Med. 2020;383(23):2207-2218. doi:10.1056/NEJMoa2017699

2. Tournigand C, André T, Achille E, et al. FOLFIRI followed by FOLFOX6 or the reverse sequence in advanced colorectal cancer: a randomized GERCOR study. J Clin Oncol. 2004;22(2):229-237. doi:10.1200/JCO.2004.05.113

3. Grothey A, Van Cutsem E, Sobrero A, et al; CORRECT Study Group. Regorafenib monotherapy for previously treated metastatic colorectal cancer (CORRECT): an international, multicentre, randomised, placebo-controlled, phase 3 trial. Lancet. 2013;381(9863):303-312. doi:10.1016/S0140-6736(12)61900-X

4. Bekaii-Saab TS, Ou FS, Ahn DH, et al. Regorafenib dose-optimisation in patients with refrac- tory metastatic colorectal cancer (ReDOS): a randomised, multicentre, open-label, phase 2 study. Lancet Oncol. 2019;20(8):1070-1082. doi:10.1016/S1470-2045(19)30272-4

5. Mayer RJ, Van Cutsem E, Falcone A, et al; RECOURSE Study Group. Randomized trial of TAS-102 for refractory metastatic colorectal cancer. N Engl J Med. 2015;372(20):1909-1919. doi:10.1056/NEJMoa1414325

6. Sonbol MB, Benkhadra R, Wang Z, et al. A systematic review and network meta- analysis of regorafenib and TAS-102 in refractory metastatic colorectal cancer. Oncologist. 2019;24(9):1174-1179. doi:10.1634/theoncologist.2019-0189

During a virtual Targeted Oncology Case-Based Peer Perspectives event, Dr. Tanios Bekaii-Saab discussed the chemotherapy and targeted treatment options available for the treatment of patients with metastatic colorectal cancer with participating oncologists. 

Bekaii-Saab Explores Chemotherapies and Targeted Treatment Options in Metastatic CRC

Tanios S. Bekaii-Saab, MD, consultant, Division of Hematology/Oncology, Department of Internal Medicine, Mayo Clinic, discusses genetic testing and emerging precision medicine strategies in the field of colorectal cancer (CRC).

As part of the Academic and Community Cancer Research United (ACCRU) research consortium, multiple clinical trials are using genetic information obtained from roughly 6,000 patients with CRC across 16 centers. The study known as COLOMATE utilizes both liquid and tissue biopsy to identify genetic alterations in patients with CRC, say Bekaii-Saab. Other research includes the PULSE study (NCT03992456) of panitumumab (Vectibix), regorafenib (Stivarga), or TAS-102 (Lonsurf) as treatment of patients with metastatic and/or unresectable RAS wild-type disease. Finally, the MOUNTAINEER study (NCT03043313) of tucatinib trastuzumab in patients with HER2-positive disease is also underway as part of ACCRU. Presentations on these studies occurred during the 2021 Gastrointestinal Cancers Symposium.

Outside of these studies, Bekaii-Saab says there are basket trials that cover 

G12C-mutated disease. The hope is that the landscape continues to expand and CRC will become classified as multiple diseases based on the genetic alterations found in patients.

Tanios S. Bekaii-Saab, MD, discusses genetic testing and emerging precision medicine strategies in the field of colorectal cancer.

Tanios Bekaii -Saab, MD | Authors

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