Jason Broderick

Data from a recent study demonstrated that increased prostate-specific antigen (PSA) screening was associated with improved outcomes in younger Black patients with prostate cancer.

Among this patient population, an increased frequency of PSA screening was linked to a nearly 25% reduction in prostate cancer–specific mortality and an approximately 40% lower risk of having metastatic disease at the time of a prostate cancer diagnosis.

“We found that PSA screening was associated with a decreased risk of … metastatic disease at diagnosis, as well as prostate cancer–specific mortality. Taken together, these results would suggest that [increased] PSA screening may improve cancer outcomes for young African American men,” said lead study author Edmund M. Qiao, of the University of California San Diego, during a presentation of the data on a news briefing held ahead of the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting.

A blood test and PSA screening may indicate the presence of prostate cancer. However, other conditions, such as an inflamed prostate, can increase PSA levels, which is why there is conflicting advice involving screening.

Overall, the study included 4,726 Black men (mean age, 51.8 years) diagnosed with prostate cancer. The “high PSA screening” group had received an average of three prior screening tests and the “low PSA screening” group had received an average of 0.5 prior screening tests.

Regarding disease severity at diagnosis, all important metrics showed that the high PSA screening group had lower severity. The rate of metastatic disease at diagnosis was 4.2% versus 1.4%, respectively, translating to a 39% risk reduction.

“In our statistical model, controlling for the confounders, we found that PSA screening was associated with about a 25% reduction in prostate cancer–specific mortality,” noted Qiao. The confounding factors controlled for in the statistical model included primary care visit rate, age at diagnosis, year of diagnosis, employment, marital status, college education and income.

Black men have the highest mortality rate in prostate cancer, Qiao noted. Prior to this research, he highlighted, there has been limited data on PSA screening in this patient population.

“The data for PSA screening includes very few African American men (in general) and no young African American men between the ages of 40 and 55,” he said. “This has led to discordant PSA screening recommendations for these patients and as a result, young African American men are an at-risk group that needs additional research to help guide their clinicians and themselves when deciding when to start PSA screening.”

In 2012, the U.S. Preventive Services Task Force (USPSTF) issued a grade D recommendation against the use of PSA screening in the general U.S. population, regardless of age. The current USPSTF PSA screening policy is slightly changed, with a grade C recommendation for men aged 55 to 69 years, meaning in this population, an individual decision on screening should be made based on a physician-clinician discussion of the potential benefits and risks.

While the USPSTF acknowledges that family history and Black race are two of the most significant risk factors for developing prostate cancer, the panel maintains that there is insufficient evidence to issue individualized screening recommendations in any age group based on those factors.

“We know African American men are nearly one-and-a-half times more likely to develop prostate cancer and more than twice as likely to die from prostate cancer as White patients,” ASCO President Dr. Lori J. Pierce said during the news briefing. “And despite this, young African American men are poorly represented in PSA studies from which evidence-based guidelines are developed. So, this really limits proper PSA guidance screening guidance for African American patients, especially for those who are younger than 55. And so, because we don't have adequate screening data, there are differences in opinion as to what the guidelines should be. And so, this abstract makes a very strong statement to discuss screening at a younger age in African American men.”

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The study results lend strength to discuss prostate cancer screening in younger Black men, according to an expert.

Increased Screening Associated with Improved Outcomes in Younger Black Patients with Prostate Cancer

Sprycel (dasatinib), an oral medication that helps reduce the production of damaged white blood cells in the body, has been approved by the Food and Drug Administration (FDA) for the treatment of pediatric patients with Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia (CML) in chronic phase (CP).

The approval is based on results with Sprycel demonstrated in 97 pediatric patients with CP-CML enrolled across two studies, an open-label, nonrandomized, single-arm phase 2 trial and an open-label, nonrandomized, dose-ranging phase 1 trial. Fifty-one patients (all from the single-arm trial) were newly diagnosed, and the remaining 46 (29 from the single-arm study and 17 from the dose-ranging trial) were intolerant or resistant to prior Gleevec (imatinib).

At a median follow-up of 4.5 years, more than half of the responding patients in the treatment-naïve cohort had not progressed at the time of the data cutoff, so the median duration of complete cytogenetic response (CCyR), major cytogenetic response (MCyR), and major molecular response (MMR) could not be estimated. The same was true at the median follow-up time of 5.2 years for the previously treated cohort.

The range of duration of response (DOR) for the newly diagnosed patients was 2.5+ to 66.5+ months for CCyR, 1.4 to 66.5+ months for MCyR, 5.4+ to 72.5+ months for patients who achieved MMR by month 24, and 0.03+ to 72.5+ months for patients who achieved MMR at any time. The ‘+’ denotes a censored observation. Among the Gleevec-intolerant cohort, the DOR ranges were 2.4 to 86.9+ months for CCyR, 2.4 to 86.9+ months for MCyR, and 2.6+ to 73.6+ months for MMR.

“Options for pediatric patients with chronic myeloid leukemia are limited, and it is challenging to conduct clinical trials investigating potential new treatments in this small patient population,” Lia Gore, M.D., University of Colorado School of Medicine and Children’s Hospital Colorado, said in a statement. “Dasatinib is an important new option to help address the unmet needs of children with Philadelphia chromosome-positive CML in chronic phase.”

The 3-, 6-, 12- and 24-month CCyR rates among newly diagnosed patients were 43.1 percent, 66.7 percent, 96.1 percent and 96.1 percent, respectively. In the previously treated group, the corresponding rates were 45.7 percent, 71.7 percent, 78.3 percent and 82.6 percent, respectively.

The 3-, 6-, 12- and 24-month MCyR rates among treatment-naive patients were 60.8 percent, 90.2 percent, 98.0 percent and 98.0 percent, respectively. The corresponding rates in the Gleevec-intolerant group were 60.9 percent, 82.6 percent, 89.1 percent and 89.1 percent, respectively.

The 3-, 6-, 12- and 24-month MMR rates among newly diagnosed patients were 7.8 percent, 31.4 percent, 56.9 percent and 74.5 percent, respectively. The corresponding rates in the previously treated group were 15.2 percent, 26.1 percent, 39.1 percent and 52.2 percent, respectively.

Across both patient groups, 14.4 percent experienced treatment-related serious adverse events (AEs). AEs occurring in 15 percent or more of patients included myelosuppression, headache, nausea, diarrhea, skin rash, pain in extremity and abdominal pain.

“While chronic myeloid leukemia is rare in children, accounting for less than three percent of all pediatric leukemias, it is often more aggressive in younger patients than in adults and until recently, there have been few available treatment options,” Vickie Buenger, President, Coalition Against Childhood Cancer, said in a statement. “The FDA’s decision to approve the expanded use of Sprycel in children with Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase may bring new hope to these patients and their families.”

Sprycel (dasatinib), an oral medication that helps reduce the production of damaged white blood cells, has been approved by the Food and Drug Administration for the treatment of pediatric patients with Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase.
 

Sprycel Approved for CML Subset

The FDA has granted an accelerated approval to Tecentriq (atezolizumab) as a frontline treatment for patients with locally advanced or metastatic urothelial carcinoma (mUC) who are not eligible for cisplatin chemotherapy. The approval was announced by Genentech, the immunotherapy drug’s manufacturer.

“It is encouraging to see continued progress in the treatment of advanced bladder cancer, which until last year had not seen any major advancements in more than 30 years,” said Andrea Maddox Smith, chief executive officer, Bladder Cancer Advocacy Network. “We are excited that Tecentriq is now a treatment option for people with advanced bladder cancer who are unable to receive a cisplatin-based chemotherapy as an initial treatment.”

The approval is based on data from the single-arm phase II IMvigor210 trial. In a study cohort of 119 cisplatin-ineligible, treatment-naive patients, the objective response rate with Tecentriq was 23.5 percent, including a complete response rate of 6.7 percent.

Tecentriq was previously approved for people with locally advanced or mUC who have disease progression during or following any platinum-containing chemotherapy, or within 12 months of receiving chemotherapy before surgery or after surgery.

“We are pleased that Tecentriq will now be available to more people with advanced bladder cancer, including those who are unable to receive initial treatment with cisplatin chemotherapy,” said Sandra Horning, MD, chief medical officer and head of Global Product Development at Genentech.

“Tecentriq was the first cancer immunotherapy approved by the FDA for people with advanced bladder cancer and has become a standard of care in those whose disease has progressed after receiving other medicines, either before or after surgery, or after their disease has spread.”

The IMvigor210 cohort enrolled 123 patients with cisplatin-ineligible locally advanced or mUC at 47 locations in North America and Europe between June 9, 2014, and March 30, 2015. Patients received 1200 mg of intravenous Tecentriq every three weeks until progression. The primary endpoint was objective response rate, with secondary outcomes measures including progression-free survival and overall survival.

Among the 123 patients, 119 received at least one dose of Tecentriq. Responses occurred regardless of PD-L1 status and across poor prognostic factor subgroups. The median duration of response was not reached. There was an association between tumor mutation load and response. The median progression-free survival was 2.7 months and overall survival was 15.9 months.

The most common grade 3/4 adverse events included fatigue (8 percent), urinary tract infection (5 percent), anemia (7 percent), diarrhea (5 percent), increase in the level of creatinine in the blood (5percent), increase of the liver enzyme alanine transaminase (4 percent), hyponatremia (15percent), decreased appetite (3 percent), and back/neck pain (3 percent).

Adverse events led to 5 patients discontinuing treatment. Five patients died, due to sepsis, cardiac arrest, myocardial infarction, respiratory failure, and respiratory distress. An additional patient had inflammation of the brain due to the herpes simplex virus and disease progression at the time of death.

The accelerated approvals of Tecentriq are contingent on results from an ongoing confirmatory phase III study, IMvigor 211 (NCT02302807), which is comparing Tecentriq with chemotherapy in patients with locally advanced or metastatic urothelial bladder cancer in the frontline setting and after progression on at least one prior platinum-containing regimen.

The FDA has granted an accelerated approval to Tecentriq as a frontline treatment for patients with locally advanced or metastatic urothelial carcinoma who are not eligible for cisplatin chemotherapy.

Tecentriq Approved as First-Line Treatment for Some Patients With Bladder Cancer

The PALOMA-3 trial examining an Ibrance (palbociclib) regimen in HR-positive/HER2-negative breast cancer was halted after an independent panel determined it met the primary endpoint of improving progression-free survival (PFS). The results were announced by Pfizer, the company developing Ibrance, which noted that these are the first randomized phase 3 data reported for the CDK 4/6 inhibitor.

“We’re gratified to be able to stop the trial early and are engaging in discussions with health authorities regarding a regulatory path forward,” Mace Rothenberg, senior vice president of Clinical Development and Medical Affairs and chief medical officer for Pfizer Oncology, said in a statement.

The multicenter PALOMA-3 study randomized 521 patients with metastatic breast cancer whose disease progressed on or following endocrine treatment in a 2:1 ratio to fulvestrant plus either placebo or Ibrance. Faslodex was administered at 500 mg (IM) on days 1 and 15 of cycle 1, and then on day 1 of each cycle thereafter, and patients received oral Ibrance at 125 mg/day continuously for the first 3 weeks of each cycle, followed by 1 week off. Treatment cycles were 28 days for both arms.

Beyond the primary PFS endpoint, secondary endpoints for the trial included overall survival, objective response, and duration of response. The adverse events reported for the Ibrance/fulvestrant combination were commensurate with those observed with previous single-agent use of the drugs. Pfizer intends to submit the full results from the study for presentation at the 2015 American Society of Clinical Oncology (ASCO) Annual Meeting in June.

While not approved for the use explored in PALOMA-3, Ibrance has received an accelerated approval as a frontline treatment for postmenopausal women with ER-positive, HER2-negative metastatic breast cancer, based on findings from the phase 2 PALOMA-1 trial.

In the open-label phase 2 study, treatment with Ibrance plus letrozole reduced the risk of disease progression by 51 percent compared with letrozole alone. The median PFS with Ibrance was 20.2 versus 10.2 months for letrozole alone.

PALOMA-1 trial randomized 165 postmenopausal patients with ER-positive, HER2-negative advanced breast cancer in a 1:1 ratio in two parts: Part 1 contained 66 patients and Part 2 had 99 patients. Continuous daily letrozole was administered at 2.5 mg with or without Ibrance at 125 mg daily for 3 weeks followed by 1 week of rest until progression. The primary endpoint was PFS by investigator assessment.

The rate of grade 3/4 neutropenia was significantly higher in the Ibrance arm compared with letrozole alone (54 percent versus 1 percent). Additionally, the rate of grade 3/4 leucopenia (19 percent versus 0 percent) and fatigue (4 percent versus 1 percent) were higher with Ibrance. No cases of febrile neutropenia or neutropenia-related infections were reported in the study.

Altogether, 13 percent of patients discontinued treatment as a result of side effects in the Ibrance arm compared with 2 percent for letrozole. The most frequently reported serious adverse events with the combination were pulmonary embolism (4 percent) and diarrhea (2 percent).

At the time of approval, PALOMA-1 coauthor Dennis Slamon heralded the decision. “With the FDA approval, this study represents a potential practice-changing result. I believe palbociclib will now become a standard treatment approach for postmenopausal women with ER+/HER2- metastatic breast cancer,” Slamon, a professor of medicine and director of the Revlon/UCLA Women’s Cancer Research Program, said in a statement.

The confirmatory phase 3 trial for Ibrance's accelerated approval is PALOMA-2. This study is comparing the combination of Ibrance and letrozole with letrozole alone as a frontline treatment for postmenopausal women with ER-positive, HER2-negative advanced breast cancer (NCT01740427).

As Pfizer awaits the PALOMA-2 data, Rothenberg noted that the company is pleased with what the PALOMA-3 outcomes have shown. “The results of this trial are especially important because they help us understand the potential of Ibrance to improve outcomes in patients with this difficult to treat cancer.”

The PALOMA-3 trial examining an Ibrance (palbociclib) regimen in HR-positive/HER2-negative breast cancer was halted after an independent panel determined it met the primary endpoint of improving progression-free survival.

Ibrance Delays Progression of Breast Cancer in Phase 3 Trial

Kyprolis (carfilzomib) doubled progression-free survival (PFS) versus Velcade (bortezomib) in patients with relapsed multiple myeloma in the phase 3 ENDEAVOR trial. The results were announced by the developer of Kyprolis, Amgen, and its subsidiary Onyx Pharmaceuticals, Inc.

The head-to-head ENDEAVOR study randomized 929 patients with relapsed multiple myeloma to low-dose dexamethasone plus Kyprolis or Velcade. At a planned interim analysis, the trial met its primary endpoint with a significant improvement in PFS with Kyprolis: 18.7 versus 9.4 months.

Enrolled patients were required to have received between one and three previous treatment regimens. The international trial was conducted at 235 locations.

Treatment with Kyprolis reduced the risk of disease progression by 47 percent versus Velcade. Results were also superior with Kyprolis for the secondary outcome measures of overall response rate (ORR) and lower incidence of neuropathy. Data for overall survival (OS) have not yet matured.

Adverse event (AE)—induced treatment discontinuations and on-study deaths were similar between the two treatment groups. The rates for cardiac and renal failure were higher in the Kyprolis arm versus the Velcade arm. These rates were comparable to those reported in the pivotal phase 3 ASPIRE study, which examined Kyprolis, Revlimid (lenalidomide) and low-dose dexamethasone versus Revlimid, and low-dose dexamethasone alone in 792 patients with relapsed multiple myeloma.

The frequency of dyspnea and hypertension in the Kyprolis versus the Velcade arm in ENDEAVOR increased compared with the incidents reported in ASPIRE. 

Amgen intends to submit full data for ENDEAVOR for presentation at the 2015 ASCO Annual Meeting this summer.

The Food and Drug Administration (FDA) granted an accelerated approval to Kyprolis in July 2012 as a treatment for patients with multiple myeloma following at least two therapies, including Velcade and an immunomodulatory agent. This indication was based on data from a single-arm clinical trial that enrolled 266 patients with relapsed multiple myeloma who received at least two prior therapies. In this study, the ORR with Kyprolis was 22.9 percent. As a condition of the approval, Onyx was required to submit a full analysis from the ASPIRE trial.

Earlier this year, a supplemental New Drug Application was submitted to the FDA for the full regulatory approval of Kyprolis as a treatment for patients with relapsed multiple myeloma based on the results from ASPIRE. Early results from the study were announced in August 2014. Keith Stewart, from the Mayo Clinic in Scottsdale, Ariz., presented full data from the trial at the 2014 annual meeting of the American Society for Hematology held in December.

ASPIRE found that the combination of Kyprolis, Revlimid and low-dose dexamethasone reduced the risk of progression by 31 percent compared with Revlimid and low-dose dexamethasone alone in patients with relapsed multiple myeloma. The median PFS with Kyprolis was 26.3 months compared with 17.6 months without the proteasome inhibitor.

At the 24-month interim analysis, 73.3 percent of patients in the Kyprolis arm were alive versus 65 percent with the two-drug regimen. The median overall survival was not yet reached with a trend favoring the carfilzomib arm.

The ORR was 87.4 percent versus 66.9 percent and the median duration of response was 28.6 months compared with 21.2 months with and without Kyprolis, respectively. Of patients who responded, the complete response rate was 17.7 percent with Kyprolis versus 5.1 percent without and the very good partial response rate was 70.4 percent with Kyprolis versus 40.7 percent in the control arm.

Treatment discontinuation due to an adverse event occurred in 15.2 percent of patients treated with Kyprolis compared with 17.4 percent with the two-drug regimen.

The most common severe hematologic adverse events with Kyprolis compared with the control arm were neutropenia, anemia and thrombocytopenia. The most common severe nonhematologic side effect was pneumonia.

For the three-drug regimen versus the two-drug regimen, respectively, all-grade acute renal failure occurred in 8.4 percent of patients versus 7.2 percent, cardiac failure was seen in 6.4 percent of patients versus 4.1 percent, and ischemic heart disease was experienced by 5.9 percent of patients compared with 4.6 percent.

ENDEAVOR is the first of two phase 3 trials comparing Kyprolis head-to-head with Velcade in multiple myeloma. Results are still anticipated for the CLARION study, in which the two drugs, in combination with melphalan and prednisone, are being compared in the frontline setting (

Kyprolis doubled progression-free survival versus Velcade in patients with relapsed multiple myeloma in the phase 3 ENDEAVOR trial. 

Kyprolis Doubles Progression-Free Survival Over Velcade in Multiple Myeloma Trial

The vastly improved outlook for patients with chronic lymphocytic leukemia (CLL) was named the American Society of Clinical Oncology's inaugural “Cancer Advance of the Year.” Specifically, the country's leading professional oncology organization is recognizing the approval of four new therapeutic options for CLL over the past two years: Gazyva (obinutuzumab), Imbruvica (ibrutinib), Arzerra (ofatumumab) and Zydelig (idelalisib).

The announcement was made as part of ASCO’s release of its annual update on oncology treatment advances: 

Clinical Cancer Advances 2015: ASCO's Annual Report on Progress Against Cancer

“These new therapies fill an enormous need for thousands of patients living with CLL,” said Gregory Masters, ASCO expert and co-executive editor of the report, in a statement. “For many older patients, especially, these drugs essentially offer the first chance at effective treatment, since the side effects of earlier options were simply too toxic for many to handle.”

The immunotherapies (Gazyva) and ofatumumab (Arzerra) are approved in the frontline CLL setting, while the small-molecule inhibitors Imbruvica and Zydelig are approved for resistant/relapsed CLL.

The first of these four agents approved over 2013 and 2014 was the anti-CD20 agent Gazyva . In November 2013, the FDA approved the drug in combination with chlorambucil as a first-line treatment regimen for patients with CLL based on data from the phase 3 CLL11 trial. In the study, the Gazyva/chlorambucil combination significantly reduced the risk of progression by 84 percent, when compared with chlorambucil alone. 

In December 2014, the FDA updated the label for Gazyva plus chlorambucil to include data from stage 2 of the CLL11 study, which detailed an unprecedented 11.8-month improvement in progression-free survival (PFS) compared with Rituxan (rituximab) plus chlorambucil as a frontline treatment for patients with CLL (26.7 months  compared with 14.9 months.

The next new option approved for patients with CLL was the BTK inhibitor Imbruvica in February 2014. The FDA approved the agent for patients with CLL who have received at least one previous therapy. The decision was based on data from 48 patients enrolled in the single-arm phase 1b/2 PCYC-1102-CA study. At a median 15.6-month follow-up for this group, single-agent Imbruvica produced an overall response rate (ORR) of 58.3 percent (all partial responses) with a duration of response of up to 24.2 months.

The most common grade 3/4 nonhematological adverse reactions were pneumonia, hypertension, dehydration, atrial fibrillation, and sinusitis. Additionally, Imbruvica-related grade 3/4 cytopenias were reported in 35 percent of patients.

In July 2014, the FDA expanded the approval of Imbruvica to include the treatment of patients with CLL who harbor a 17p deletion, based on findings from the phase 3 RESONATE trial. In RESONATE, Imbruvica lowered the risk of progression by 75 percent in patients with CLL who harbored a 17p deletion and by 78 percent in the full population of the study when compared with Arzerra.

The anti-CD20 agent Arzerra, which received a new indication in April 2014, marked the third new CLL treatment option made available over the past couple of years. The indication is for Arzerra plus chlorambucil for previously untreated patients with CLL who are considered inappropriate for treatment with the chemotherapy fludarabine. The FDA first approved Arzerra in October 2009 for the treatment of patients with CLL who no longer respond to chemotherapy.

The new approval was based on results from the phase 3 COMPLEMENT 1 trial, in which Arzerra and chlorambucil demonstrated a 9.3-month improvement in PFS compared with chlorambucil alone. The ORR with the combination was 82 percent versus 69 percent with chlorambucil alone.

Grade 3/4 adverse events occurred in 50 percent of patients treated with ofatumumab compared with 43 percent in the chlorambucil monotherapy arm. The most common grade 3/4 toxicity was neutropenia, which occurred in 26 percent of patients treated with Arzerra compared with 14 percent for chlorambucil alone. Grade 3/4 infusion-related adverse events were reported in 10 percent of patients treated with Arzerra compared with none for those receiving chlorambucil alone.

And rounding out the impressive 2013/2014 breakthroughs in CLL care was the July 2014 approval of the PI3K-delta inhibitor Zydelig in combination with Rituxan for patients with high-risk relapsed or refractory CLL. The approval was based on the phase 3 Study 116 trial, in which the addition of Zydelig to Rituxan improved overall survival by 72 percent and PFS by 82 percent versus placebo and Rituxan.

In a statement on the naming of these CLL breakthroughs as the Cancer Advance of the Year, ASCO President Peter P. Yu, MD, said, “This has truly been a banner year for CLL and for clinical cancer research as a whole. Advances in cancer prevention and care, especially those in precision medicine, are offering stunning new possibilities for patients.”

, now in its 10th year, was published online in the 

. The 2015 report was developed by an editorial board of 18 experts representing a wide spectrum of oncology specialties. Beyond announcing the top advancement in cancer, this year’s report also includes a look back at the last 10 years in oncology and a look forward at projected trends for the next decade, as well as sections on the top research advances from the past year and promising early advances in rare cancers.

The vastly improved outlook for patients with chronic lymphocytic leukemia (CLL) was named the American Society of Clinical Oncology's inaugural "Cancer Advance of the Year." 

ASCO Selects Dramatic Improvement in CLL Care as 'Cancer Advance of the Year'

Research presented at the 2014 San Antonio Breast Cancer Symposium shows that high levels of lymphocytes, white blood cells found in the immune system, could help identify women with HER2-positive breast cancer who could forego chemotherapy.

	According to a subset analysis in the phase 3 N9831 trial, researchers found that among patients who were treated with chemotherapy alone, women who had high levels of stromal tumor-infiltrating lymphocytes (S-TILs) had an 80 percent lower likelihood of disease recurrence compared with those with lower TIL counts. The study also uncovered that there was not a similar association between higher S-TIL levels and improved outcomes among patients in N9831 who received standard care with Herceptin (trastuzumab) plus chemotherapy.

	Taken together, the findings suggest higher TIL levels may be a biomarker used to identify patients for whom optimal treatment might be chemotherapy alone, sparing the patient from HER2-targeted treatment, suggested Edith Perez, who presented the data at the meeting.

	“The message here is that for the patients whose tumors are highly infiltrated with lymphocytes, we cannot prove that there is a benefit to using chemotherapy plus trastuzumab, at least based on the trend that we observed in this study,” said Perez, deputy director at large for the Mayo Clinic Cancer Center. She cautioned, however, that she is not yet recommending changing clinical practice.

	“We need to do additional studies to corroborate our findings. I would not change the standard of care today,” Perez said. Previous research has suggested a prognostic value for TILs in triple-negative breast cancer. A study published earlier this year also reported that higher S-TIL levels were linked to a greater Herceptin benefit among a subset of 209 patients with HER2-positive breast cancer from the FinHER trial. The N9831 subset analysis reported at SABCS is the largest analysis to date of the prognostic and predictive value of S-TILs in breast cancer, noted Perez.

	The pivotal, three-arm N9831 trial demonstrated improved clinical outcomes when adding Herceptin sequentially or concurrently to chemotherapy in women with non-metastatic HER2-positive breast cancer. The subset analysis that Perez reported included samples from primary tumors of patients enrolled in two of the three N9831 arms: the chemotherapy alone cohort (doxorubicin and cyclophosphamide, followed by paclitaxel) and the concurrent Herceptin cohort (doxorubicin and cyclophosphamide followed by concurrent paclitaxel plus Herceptin, and then Herceptin monotherapy). Using international consensus guidelines, S-TILs were examined for 489 patients from the chemotherapy-alone group and 456 patients from the concurrent Herceptin group.

	Patients with at least 60 percent S-TIL counts were considered to have high levels (at least 60 percent of cells in the tumor sample were immune cells). Overall, 94 patients met the high S-TIL criterion, including 48 patients in the chemotherapy-alone cohort and 46 patients in the Herceptin/chemotherapy group.

	At a median follow-up of 6.9 years, higher S-TIL levels in the chemotherapy-alone group were associated with a significant recurrence-free survival (RFS) benefit. The RFS 10-year projections in this cohort for patients with high and low S-TIL levels were 90.9 percent and 64.3 percent, respectively.

	“A high level of tumor lymphocytic infiltration was predictive of a benefit with chemotherapy,” Perez said. In the cohort that received Herceptin, there was not a link between higher S-TIL levels and improved RFS at the 6.9 year follow-up. Ten-year RFS estimates for high and low S-TIL patients in this cohort were 80 percent and 79.6 percent, respectively.

	Perez said she was “surprised” that the Herceptin results varied from the smaller FinHER analysis and offered possible explanations for the disparity. “The FinHER study utilized Herceptin for only nine weeks. [It was also] a very small study—they only had 49 total events and it was very limited in terms of statistical power,” she said. Conversely, the N9831 analysis had many more patients and a longer follow-up.

	As a separate component of their research, Perez’s group also compared the treatment arms head-to-head by S-TIL status. Among patients with high S-TIL levels, there was not a significant trend toward improved RFS in patients receiving chemotherapy alone versus combination therapy with Herceptin. In patients with low S-TIL levels, there was a significant RFS benefit for patients receiving standard of care with Herceptin versus chemotherapy alone. Going forward, Perez and her colleagues hope to conduct a similar analysis in another cohort of patients and analyze immune cell subtypes to examine whether improved outcomes are related to a specific subtype.

	Perez said she would ultimately like to examine whether patient outcomes could be improved by changing the amount and type of S-TILs.

	“It would be fascinating to see if can change the milieu of the tumor to see if we can modify sensitivity to treatments,” she said. The Breast Cancer Research Foundation and 26.2 With Donna Foundation supported the study’s research.