Oncology On The Go

In a conversation with CancerNetwork®, Rakshanda Rahman, MD, FRCS, FACS, discussed a wide range of surgical therapy strategies and other developments in the breast cancer space, ranging from factors that should be considered for surgical decision-making to the evolution of artificial intelligence (AI) in the field.


Rahman, a professor of Breast Surgical Oncology at Texas Tech University Health Sciences Center and the medical director of UMC Cancer Center, spoke about challenges associated with barriers to treatment, stating how some patients, particularly those residing in rural counties, may not have sufficient access to the latest technologically advanced care as those in other communities. She also emphasized the value of giving early breast cancer screenings to patients to match them with appropriate systemic therapies.


“We need to keep increasing the advocacy towards screening for patients,” Rahman said. “There are still a lot of misgivings in people’s minds. They may be scared of radiation or do not have time; there are lots of reasons why people choose to not have a screening. Nothing makes a bigger difference to mortality from breast cancer like screening does. All these advancements are great, but if patients do one thing, they should get screened.”


Rahman also discussed her adoption of a genomic profiling test at her clinic to more accurately predict patients who may benefit from treatment with chemotherapy or endocrine therapy. Additionally, she spoke to the use of advanced screening technologies that allow for the detection of tiny tumors, although this may present some logistical challenges for surgically removing a tumor of that size. She also highlighted her use of MOLLI®, a magnetic device that she said has produced quicker operating times compared with a standard wire-based procedure.


With respect to AI, Rahman said that processing blood tests with an algorithm may help identify genes that could affect a patient’s disease, thereby allowing practices to discern what makes a tumor develop resistance. Additionally, certain AI tools may reduce the number of imaging tests needed for a patient, thus reducing health care costs in the process. However, Rahman cautioned that these AI programs should be used responsibly, as to not replace the “human connection” that underscores the doctor/patient relationship. 

Reference


MOLLI: precision surgery made simpler. MOLLI Surgical Inc. Accessed December 13, 2023. https://shorturl.at/mvCM6

In a recent discussion with CancerNetwork®, Joleen Hubbard, MD, research collaborator with Mayo Clinic and deputy director for clinical research at Allina Health Cancer Institute in Minneapolis, Minnesota, discussed new opportunities for patients with colorectal cancer (CRC).  

In the discussion, Hubbard highlighted the potential of trastuzumab deruxtecan-nxki (Enhertu; T-DXd) in patients with HER2-expressing metastatic CRC based on studies including the phase 2 DESTINY-CRC01 trial (NCT03384940), which assessed the efficacy and safety of the agent in those who progressed after 2 or more prior regimens.1  These trials may play a role in continuing HER2 inhibition downstream after the FDA approval of trastuzumab (Herceptin) plus tucatinib (Tukysa) in patients with metastatic HER2-positive CRC.2  

Hubbard also discussed the phase 3 MOUNTAINEER-03 study (NCT03043313) and its effects in the CRC space.3 This trial assessed the safety and efficacy of frontline tucatinib and trastuzumab in patients with treatment-refractory, RAS wild-type, HER2-positive metastatic CRC. Primary endpoints for this analysis showed a clinically meaningful overall response rate of 38.1% and a median duration of response of 12.4 months. Additionally, the treatment combination was well tolerated.  

She said she is “optimistic” that moving HER2-directed therapy to the first-line setting, as seen in the MOUNTAINEER-03 study, may help outcomes for patients with metastatic CRC. 

“It’s a very exciting space,” Hubbard said. “Because it’s only 5% to 8% of patients [who have CRC], it may not get as much attention, but there’s 150,000 new cases of [CRC] diagnosed each year. So, 5% to 8% of that is a large number of patients [whom] we need to be looking at, studying, and potentially impact with these treatments.” 

References 

CancerNetwork® spoke with Govindarajan Narayanan, MD about his practice becoming the first in the United States to successfully surgically treat a patient with a liver tumor using the Epione robot, as well as the process of transitioning from CT-based image guidance to the robotic workstation in his care.1 


Narayanan, a professor of Radiology and an interventional radiologist at Miami Cardiac and Vascular Institute and the chief of Interventional Oncology at Miami Cancer Institute, both of Baptist Health South Florida, described how the use of Epione may save significant amounts of time while performing microwave ablation, cryoablation, and irreversible electroporation (IRE). Developers designed the robotic device to simplify several probe procedures, helping make large tumors more predictable to manage.2 


According to Narayanan, Epione is suitable for use in any patient for whom his practice typically performs image-guided ablations. Additionally, the device may “level the playing field” by allowing those with less experience to give highly accurate surgery, thereby increasing the availability of physicians who can offer these treatments across multiple practices.


Narayanan also described some of the potential challenges associated with adopting the Epione robot in clinic, such as adapting to the physical space that it occupies in the operating room. The device may also pose a steep learning curve with respect to procedures involving multiple needles such as cryoablation and IRE, as it is necessary to set a path that won’t cause any deflections of the needle. 


Looking ahead, Narayanan said that future technological developments may allow users to operate the robot remotely, allowing patients to receive surgery at a treatment center even if a practicing physician is not physically present.


“It’s very exciting to be at the forefront of bringing such a cutting-edge technology to mainstream clinical practice,” Narayanan said. “Everything is done with one click, so it saves a significant amount of time. And because you’re not doing multiple check scans when you place the needles, you’re saving on radiation time.”

References


1.     First patient treated in the United States with Quantum Surgical’s Epione® robot. News release. Quantum Surgical. May 24, 2023. Accessed November 6, 2023. https://shorturl.at/lzH01

2.     Epione. Quantum Surgical. Accessed November 7, 2023. https://shorturl.at/dqyL6

During an overview of the current standard of care for patients with colorectal cancer (CRC), Tanios S. Bekaii-Saab, MD noted that as molecular testing becomes more important, researchers are looking into how to best personalize therapy for optimal outcomes. He spoke with CancerNetwork® as part of an Around the Practice® program focused on testing and treatment options for patients with metastatic CRC. 


When discussing the future direction of CRC care strategies, it is possible that treatment will be tailored to the individual based on mutation status, such as BRAF V600E, said Bekaii-Saab, leader of the Gastrointestinal Cancer Program and medical director of the Cancer Clinical Research Office, and vice chair and section chief for Medical Oncology in the Department of Internal Medicine at the Mayo Clinic. 


Bekaii-Saab noted that his institution is investigating select treatments in earlier lines of therapy, as chemotherapy plus or minus a biologic is the current standard of care. He also highlighted the importance of a multidisciplinary team approach, as he knows working with radiologists, and surgeons is important to provide patients with the best care. 


At the time of the interview, fruquinintib (Fruzaqla) was pending approval for patients with previously treated metastatic CRC. On November 8, 2023, fruquintinib was granted approval based on results from the phase 3 FRESCO-2 trial (NCT04322539).1,2 Investigators of the trial reported a median overall survival of 7.4 months (95% CI, 6.7-8.2) in the fruquintinib arm vs 4.8 months (95% CI, 4.0-5.8) in the placebo arm (HR, 0.66; 95% CI, 0.55-0.80; P <.0001).


Fruquintinib will now join trifluridine/tipiracil (Lonsurf) or regorafenib (Stivarga) as part of the second-line landscape and beyond for patients with previously treated CRC, Bekaii-Saab explained.


In closing, he stated that he is optimistic about the future of CRC treatment, as there is the potential for the development of new targeted therapies, immunotherapies, and gene editing therapies that will lead to more personalized and effective treatments for CRC patients.


 “The biggest takeaway from the discussion with my esteemed colleagues today relates to further understanding the complexities that have emerged with the availability of multiple targeted options in metastatic CRC,” he concluded.

References

1.     Takeda receives U.S FDA approval of Fruzaqla (fruquintinib) for previously treated metastatic colorectal cancer. News release. Takeda. November 8, 2023. Accessed November 8, 2023. https://bit.ly/3SwkD8U

2.     Dasari A, Lonardi S, Garcia-Carbonero R, et al. Fruquintinib versus placebo in patients with refractory metastatic colorectal cancer (FRESCO-2): an international, multicentre, randomised, double-blind, phase 3 study. Lancet. Published online June 15, 2023. doi:10.1016/S0140-6736(23)00772-9

Kristen K. Ciombor, MD, MSCI, an assistant professor in the Division of Hematology/Oncology in the Department of Medicine at the Vanderbilt University Medical Center, recently spoke at an Around the Practice discussion regarding updates in the world of metastatic colorectal cancer (CRC).

In this episode of the ONCOLOGY® On the Go Podcast, she discusses treatment updates, molecular testing options, and emerging targets in CRC. Ciombor also highlighted ongoing research in the space, including the phase 3 BREAKWATER (NCT04607421)1 trial and the phase 3 MOUNTAINEER-03 (NCT05253651)2 trial. She also discussed some of the most important presentations from the 2023 European Society for Medical Oncology (ESMO) Congress, including those covering the phase 2 MOUNTAINEER study (NCT03043313)3 and the phase 3 KEYNOTE-811 trial (NCT03615326).4 Additionally, she spoke about her work in the phase 2 ECOG-ACRIN trial (NCT04751370) assessing neoadjuvant nivolumab (Opdivo) plus ipilimumab (Yervoy) in patients with microsatellite instability-high or mismatch repair deficient rectal cancer.5

“I’m hoping that we see more treatment options for patients [and that] we identify more patient subtypes that we can target and find actionable alterations for,” Ciombor said.

References

1. Kopetz S, Grothey A, Yaeger R, et al. BREAKWATER: randomized phase 3 study of encorafenib (enco) + cetuximab (cetux) ± chemotherapy for first-line (1L) treatment (tx) of BRAF V600E-mutant (BRAFV600E) metastatic colorectal cancer (mCRC). J Clin Oncol. Published online May 28, 2021. doi:10.1200/jco.2021.39.15_suppl.tps3619

2. Bekaii-Saab TS, Van Cutsem E, Tabernero J, et al. MOUNTAINEER-03: phase 3 study of tucatinib, trastuzumab, and mFOLFOX6 as first-line treatment in HER2+ metastatic colorectal cancer—Trial in progress. J Clin Oncol. Published online January 24, 2023. doi:10.1200/jco.2023.41.4_suppl.tps261

3. Strickler JH, Cercek A, Siena S, et al. Tucatinib plus trastuzumab for chemotherapy-refractory, HER2-positive, RAS wild-type unresectable or metastatic colorectal cancer (MOUNTAINEER): a multicentre, open-label, phase 2 study. Lancet Oncol. Published online May 24, 2023. doi:10.1016/S1470-2045(23)00150-X 

4. Janjigian YY, Kawazoe A, Bai Y, et al. embrolizumab plus trastuzumab and chemotherapy for HER2+ metastatic gastric or gastroesophageal junction (mG/GEJ) adenocarcinoma: Survival results from the phase III, randomized, double-blind, placebo-controlled KEYNOTE-811 study. Ann Oncol. 2023;34(suppl 2):S851-S852. doi:10.1016/j.annonc.2023.09.1424

5. Ciombor KK, Hong SC, Eng C, et al. EA2201: An ECOG-ACRIN phase II study of neoadjuvant nivolumab plus ipilimumab and short course radiation in MSI-H/dMMR rectal tumors. J Clin Oncol. Published online June 2, 2022. doi:10.1200/jco.2022.40.16_suppl.tps3644

As part of an Around the Practice program, CancerNetwork® spoke with Misako Nagasaka, MD, PhD, about her current treatment strategies for patients with lung cancer as well as relevant updates and potential advancements in the non–small cell lung cancer (NSCLC) space.


Nagasaka, a thoracic oncologist and associate clinical professor at the University of California, Irvine, discussed sequencing immunotherapy and chemotherapeutic agents depending on factors including EGFR and ALK mutations as well as a patient’s PD-L1 status. She also spoke to the importance of multidisciplinary collaboration at her practice with pulmonologists and surgeons for treating patients in the neoadjuvant and adjuvant settings.


Following the FDA approval of pembrolizumab (Keytruda) plus chemotherapyfor patients with resectable NSCLC in October 2023, Nagasaka stated that she was excited to treat those who may benefit from this regimen. The regulatory agency based its approval on data from the phase 3 KEYNOTE-671 trial (NCT03425643), which assessed the regimen among 797 patients with resectable stage II, IIIA, or IIB NSCLC. 


The median overall survival was not reached (NR; 95% CI, NR-NR) among patients receiving pembrolizumab compared with 52.4 months in those receiving placebo (95% CI, 45.7-NE; HR, 0.72; 95% CI, 0.56-0.93; P = .0103). Additionally, the median event-free survival was NR (95% CI, 34.1 months to NE) vs 17.0 months (95% CI, 14.3-22.0) in each respective arm (HR, 0.58; 95% CI, 0.46-0.72; P <.0001).


Looking ahead at ongoing research efforts, Nagasaka said that her institution is assessing how the gut microbiome may influence a patient responds to treatment, as well as any adverse effects [AEs] they may experience during therapy. Additionally, she spoke about the initiation of the phase 2 PALOMA-2 trial (NCT05498428), which will evaluate amivantamab-vmjw (Rybrevant) administered subcutaneously to those with advanced or metastatic solid tumors, including a population of patients with NSCLC harboring EGFR mutations.


“I’m very excited [to initiate the PALOMA-2 trial] because from preliminary data that I’ve seen, [AE] rates are decreased. That’s really important for patients,” Nagasaka said.

Sexual dysfunction is a common problem for patients with and survivors of cancer that often remains undertreated. It can manifest in a variety of ways, including reduced libido, sexual pain, and vaginal dryness. Jennifer A. Vencill, PhD, LP, takes a biopsychosocial approach to sexual health, helping to address the psychological aspects of sexual dysfunction.

In this episode of the ONCOLOGY On the Go Podcast, Vencill, a psychologist and sex therapist from the Mayo Clinic, spoke with CancerNetwork® about the multidisciplinary approach her team takes to address sexual dysfunction in patients, which includes a psychologist/sex therapist, medical providers, nurse educators, and pelvic floor physical therapists who can provide comprehensive care and support to help patients manage sexual dysfunction and improve their quality of life.

Often, patients will avoid seeking help as there are social stigmas associated with sexual dysfunction, Vencill says. She emphasizes the importance of talking about sexual health openly to her patients and colleagues, as well as educating the public about these challenges. Sometimes these diagnoses may be overlooked, as medical oncologists do not have much time with patients during follow-up appointments, as patients and clinicians may be more concerned about treatment options or risk of recurrence than asking about sexual health. 

To help diagnose the sexual dysfunction, Vencill will refer patients to get a full body check-up to ensure there are no underlying physical issues. This is where the pelvic floor physical therapist comes into play, as they will help address any physical needs while Vencill can address mental needs. Once that is done, she will begin to treat them and help them to adapt to a “new normal” following their cancer treatment. 

Looking towards the future, Vencill hopes to see a more normalized and open dialogue about sexual health. She also encourages patients with cancer and survivors to be flexible and adaptable in their sexual relationships, as their sexual experiences may change after cancer treatment.

“[Life during or after treatment] requires some flexibility, some adaptability, some rethinking of the script that they were used to around sex,” Vencil said. “When we get stuck in those rigid scripts, we often don’t have much room for growth and exploration. The new sexual normal after cancer treatment might look very different from what you’re used to. Sometimes that's a good thing.”

During Breast Cancer Awareness Month 2023,  Rebecca M. Shulman, MD, an assistant professor in the Department of Radiation Oncology at Fox Chase Cancer Center, and Zachary Kiss, DO, a third-year resident physician in radiation oncology at Fox Chase, spoke about findings from their study, which assessed how BRCA1/2 mutations in patients with breast cancer do not appear to affect treatment outcomes with radiotherapy. 


Shulman and Kiss presented these findings as part of a poster session at the 2023 American Society for Radiation Oncology (ASTRO) Annual Meeting.


Disease-free survival (DFS) outcomes following radiation were reported to be comparable between patients with no BRCA mutations (n = 1482) and those with BRCA-mutated disease (n = 77; P = .26). Additionally, those with BRCA1/2 mutations tended to be younger (P = .004), have higher clinical stage disease (P <.006), and were more likely to undergo mastectomy (P <.001) than patients without mutated disease.


An analysis of patients with BRCA-mutated disease also indicated that those with BRCA1 mutations (n = 31) tended to be younger than those with BRCA2 mutations (n = 46; P = .006). Moreover, a higher proportion of patients with BRCA1 mutations had estrogen receptor– or progesterone receptor–negative disease (P <.001) and higher T stage (P = .032).


Shulman and Kiss also spoke about how next steps for research may include investigating potential additional mutations and other factors that may affect sensitivity to radiotherapy among patients with disease harboring BRCA mutations. They also discussed other presentations at this year’s ASTRO meeting that may support advancement towards individualized treatment approaches in patients with breast cancer. 


“Investigating the genetic and biochemical basis of cancer is a monumental task, requiring patients, ingenuity, and a continuing investment of time and resources,” Shulman said. “It’s important to communicate that progress in cancer treatment has been enormous, but that it is also incremental by nature and will require the efforts of many researchers pursuing many different ideas.”

In this episode of  the ONCOLOGY On the Go Podcast, Arvind N. Dasari, MD, and Cathy Eng, MD, speak to data supporting fruquintinib (Elunate), a VEGFR-1, -2, and -3 inhibitor as a potential treatment for patients with metastatic colorectal cancer (CRC).


Dasari is an associate professor in the Department of Gastrointestinal Medical Oncology in the Division of Cancer Medicine at The University of Texas MD Anderson Cancer Center in Houston, Texas. Eng is a David H. Johnson Chair in Surgical and Medical Oncology, a professor of medicine, co-leader of the Gastrointestinal Cancer Research Program, co-director of gastrointestinal oncology, and director of the Young Adults Program at Vanderbilt-Ingram Cancer Center in Nashville, Tennessee, and co-chair of the National Cancer Institute Gastrointestinal Steering Committee.


These experts reviewed data from the phase 3 FRESCO-2 trial (NCT04322539), which assessed the efficacy of fruquintinib compared with placebo among patients with heavily pretreated metastatic, refractory CRC. The median overall survival (OS) in the fruquintinib and placebo arms, respectively, were 7.4 months (95% CI, 6.7-8.2) and 4.8 months (95% CI, 4.0-5.8), meeting the trial’s primary end point (HR, 0.66; 95% CI, 0.55-0.80; P <.0001). According to findings from a quality-of-life (QOL) analysis of the FRESCO-2 trial, QOL and time to deterioration appeared to improve in the fruquintinib arm, as well.


The discussion also focused on how fruquintinib may impact the treatment landscape if it were to receive approval from the FDA in the previously described patient population.  


“I’ve been impressed, and I am eagerly awaiting the potential approval, given the efficacy and the good [adverse effect] profile,” Dasari said. “I think [fruquintinib] will be a standard of care for patients with metastatic colorectal cancer.” 


Eng also discussed the agent’s potentially implications in select patient subgroups.


“We need to find additional treatment options for microsatellite instability [MSI]–stable patients,” Eng noted. “[Fruquintinib] just gives another opportunity to them, with good [QOL] and improved [OS]. By improving their [OS], it improves their own personal [QOL], as well as their ability to potentially participate in another clinical trial.”


The FDA granted priority review to fruquintinib for patients with previously treated metastatic CRC in May 2023. The regulatory agency set a Prescription User Fee Act date of November 30, 2023 for fruquintinib in this indication.


Don’t forget to subscribe to the “Oncology On-The-Go” podcast on Apple Podcasts, Spotify, or anywhere podcasts are available.

CancerNetwork® spoke with experts across multiple disciplines about the far-reaching impacts of the ongoing shortages of chemotherapy drugs including carboplatin and cisplatin, and how practices may be able to mitigate these challenges in the short and long term. 


Michael Ganio, PharmD, MS, BCPS, FASHP, described the causes of carboplatin and cisplatin being in short supply across the United States and how the FDA is working with Chinese manufacturers to import these chemotherapy agents. Ganio, senior director of Pharmacy Practice and Quality at the American Society of Health-System Pharmacists, stated that communication is paramount among all members of a care team to help prevent critical errors while treating patients with limited supplies of these drugs. He also spoke about how reaching out to local representatives may help address the issues resulting from these shortages.


“Advocacy is needed,” Ganio said. “Our policymakers need to know that these shortages are having a real-world impact, and that they need to be addressed.”


Brian Slomovitz, MD, MS, FACOG, spoke about how he is managing the ongoing shortages in the context of his gynecologic cancer care, including swapping one platinum-based drug for another during treatment. Slomovitz, a gynecologic oncologist, director of Gynecologic Oncology, and co-chair of the Cancer Research Committee at Mount Sinai Medical Center in Miami Beach, Florida and a professor of Obstetrics and Gynecology at Florida International University, also described the challenges many practices across the country have due to lacking platinum-based drugs altogether.


“I know there are institutions that don't have [platinum-based chemotherapy],” Slomovitz said. “There are institutions that aren't able to give their patients the best standard-of-care therapy and aren't able to enroll patients in trials because of lack of therapy.” 


Lucio N. Gordan, MD, addressed the financial impacts of these shortages, discussing how his practice has managed the rising prices of carboplatin and cisplatin in the country. Gordan, president and managing physician at Florida Cancer Specialists & Research Institute who sees patients in the state-wide practice's Gainesville Cancer Center, stated that efforts from major oncology organizations may help increase adequate access to chemotherapy drugs.


“It's very important that the large practices and institutions in the country stay united,” Gordan said. “The Community Oncology Alliance [COA], American Society of Clinical Oncology [ASCO], and others are trying to push legislation that would protect the consumer, the patients, and us to make sure that we have a proven supply.”


Don’t forget to subscribe to the “Oncology On-The-Go” podcast on Apple Podcasts, Spotify, or anywhere podcasts are available.