Oncology Experts Reflect on Key Takeaways from Data Presented at ASCO Annual Meeting

The 2018 ASCO Annual Meeting has wrapped, with over 40,000 people in attendance and over 5000 abstracts presented from June 1-5 in Chicago, Illinois. Data from several phase III trials in lung cancer were presented, with especially significant results in non—small cell lung cancer (NSCLC). Other areas with exciting research presented during the meeting included breast, gastrointestinal, genitourinary, and hematologic cancers.

The data presented demonstrate potential for a change in the standard of care across several settings. A major topic at ASCO included the reduction of chemotherapy in many diseases, including lung cancer, breast cancer, and follicular lymphoma.

ASCO POLL: In what area do you think the most important data came from at the 2018@ASCOAnnual Meeting? Tell us in the comments what your favorite#ASCO18abstracts were, and tag your colleagues to hear their opinions.

— Targeted Oncology (@TargetedOnc)June 5, 2018

In a Twitter poll,Targeted Oncologyfollowers were in agreement that the most important data to come out of the meeting was in the field of lung cancer. Specifically in NSCLC, some of the biggest data shared included success with agents including pembrolizumab (Keytruda), LOXO-292, and dacomitinib. Another big discussion included the results from a trial investigating the possibility of detecting lung cancer early with cell-free DNA (cfDNA) assays.

“Immunotherapy ruled the day in NSCLC at ASCO,” David R. Gandara, MD, of UC Davis Comprehensive Cancer Center, toldTargeted Oncology. “The studies presented either clarified and simplified decision-making or made it much more complex. Beauty is in the eyes of the beholder, as the saying goes.”

A change in the standard of care is expected for the treatment of (HR)-positive, HER2-negative, node-negative early-stage breast cancer. While chemoendocrine therapy has been the standard, new data from the TAILORx trial show chemotherapy may not be necessary in some patients.

Another trial also looked at metastatic triple-negative breast cancer (TNBC) and demonstrated disease control with a poly (ADP-ribose) polymerase (PARP) inhibitor and an anti-PD-1 inhibitor. Previous studies showed potential for a synergistic interaction between these 2 agents.

“The biggest takeaway is about how to de-escalate the treatment in breast cancer,” said Naoto T. Ueno, MD, PhD, FACP, of MD Anderson Cancer Center. “We are now in the era that requires both enhancing treatment efficacy as well as improving quality of life by prospective clinical studies. Any future trials are expected to meet both criteria.”

Here are some of the top abstracts presented at the 2018 ASCO Annual Meeting:

New Potential Adjuvant Standard of Care With mFOLFIRINOX in Pancreatic Cancer

Data from a phase III study demonstrated a modified FOLFIRINOX (mFOLFIRINOX) 4-drug treatment regimen dramatically improved survival in patients with resected pancreatic cancer. The median overall survival (OS) for patients receiving mFOLFIRINOX was 20 months longer than those receiving the standard of care, gemcitabine, in the postoperative setting. There was also a 36% reduction in the risk of death and a median disease-free survival 8.8 month longer than with gemcitabine.

“In the adjuvant approach to pancreatic ductal adenocarcinoma (PDAC), I think that the data in favor of FOLFIRINOX over gemcitabine are practice-changing insofar as I have never seen a median survival in PDAC of this length,” Mark A. Lewis, MD, of Intermountain Healthcare, toldTargeted Oncology.

“I think the real key will be patient selection; determining whom under their care can tolerate a triplet within months of a Whipple operation will require significant discretion by treating oncologists,” Lewis added.

Sunitinib Alone Shows Noninferiority Versus Standard of Care in mRCC

In the CARMENA trial, sunitinib (Suntent) as a monotherapy proved to be nonsuperior to the combination regimen of sunitinib plus cytoreductive nephrectomy for patients with synchronous metastatic renal cell carcinoma (mRCC). There was a median OS benefit of 18.4 months in patients treated with sunitinib alone versus the combination. These results demonstrate that nephrectomy is no longer a necessary part of treatment for these patients.

“CARMENA was a well-designed, clinically important, and difficult to perform study,” Scott T. Tagawa, MS, MD, of Weill Cornell Medicine, said. “This is important in that it changes the standard of care for the average patient that is initially diagnosed with RCC in the setting of metastatic disease. Though we can’t conclude superiority based upon the non-inferiority design, it appears that patients without initial nephrectomy actually did better for progression-free and overall survival.”

KEYNOTE-042 Data Suggest Survival Improvement With Pembrolizumab in NSCLC

OS was improved by 4 to 8 months in patients with NSCLC when treated with frontline pembrolizumab versus the standard of care, chemotherapy. Patients receiving pembrolizumab also experienced significantly less AEs (17.8%) when compared to chemotherapy treatment (41%).

Early Stage Lung Cancer Detected with cfDNA Assays

Initial results from a study investigating 3 prototype sequencing assays utilizing cfDNA demonstrated high degrees of specificity in identifying signs of early stage lung cancer. These findings suggest it may be possible to detect lung cancer in the future with a noninvasive screening, such as a blood sample, during a routine doctor visit.

LOXO-292 Induces 77% ORR in RET-Positive Tumors

In the phase I LIBRETTO-001 trial, 77% of patients with RET fusion-positive non—small cell lung cancer (NSCLC) who received LOXO-292, a highly-selective RET inhibitor, had a response. Also, no patients experienced progressive disease as of the April 2018 data cutoff. The treatment was also well tolerated, with mostly grade 1 treatment-emergent adverse events (TEAEs) and only 2 grade 3 TEAEs. Enrollment will continue for this trial until August 2019, the primary completion date.

Dacomitinib Proves Superior to Gefitinib as Frontline Treatment for EGFR-Mutant NSCLC

Updated findings from the phase III ARCHER 1050 trial showed an improved median OS of 34.1 months in patients with advanced, EGFR-mutant NSCLC when treated with the tyrosine kinase inhibitor (TKI) dacomitinib, in comparison to 26.8 months with gefitinib (Iressa). These agents were compared in the frontline setting, where dacomitinib demonstrated potential as a frontline treatment forEGFRmutation-positive NSCLC.

Adjuvant Endocrine Therapy Noninferior to Chemoendocrine Therapy for Intermediate Risk Breast Cancer

The phase III TAILORx trialdemonstrated that adjuvant endocrine therapy was noninferior to chemoendocrine therapy for patients with HR-positive, HER2-negative, node-negative early-stage breast cancer. While this is one of the most common types of breast cancer, this data can potentially save thousands of women from overtreatment with chemotherapy. For women with a greater risk of recurrence, it is still recommended they receive some form of chemotherapy.

“The TAILORx study is a game changer study,” Ueno said.  “Many patients will be spared from receiving adjuvant chemotherapy for those who have intermediate risk score with ER+/HER2- node negative primary breast cancer.”

Activity in Relapsed Progressive TNBC With Niraparib Plus Pembrolizumab

In a trial investigating the combination of the PARP inhibitor niraparib (Zejula) and PD-1 inhibitor pembrolizumab, 13 of 46 patients with metastatic TNBC had objective responses. Ten patients also had stable disease and clinical activity was observed in patients with germlineBRCAmutations.

Promise in First-Line Setting for Follicular Lymphoma

According to the phase III RELEVANCE trial investigating combination rituximab (Rituxan) plus lenalidomide (Revlimid), similar efficacy was found with this chemotherapy-free treatment as rituximab plus chemotherapy for treatment-naïve patients with follicular lymphoma. There was, however, a more favorable toxicity profile with the chemotherapy-free regimen, which shows this may be a promising new combination for these patients.  

IMPACT Study Shows Benefit of Matched Targeted Therapies for Hard-to-Treat Cancers

Data from the IMPACT trial showed improved OS with personalized therapy based on tumor molecular profiling in patients with advanced, hard-to-treat cancers. OS rates were more favorable in a group of patients receiving matched targeted therapy versus those that did not receive precision therapy at both the 3-year (15% vs. 7%) and the 10-year mark (6% vs. 1%), respectively. Matched therapy also had a superior progression-free survival.

The cancers included in this study were gastrointestinal (24.2%), gynecologic (19.4%), breast (13.5%), melanoma (11.9%), and lung (8.7%). These results are being tested further in the ongoing IMPACT2 trial, as well as ASCO’s TAPUR trial.

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