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Just In... Meeting News
Key news updates and reports from the latest meetings in oncology and hematology.

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Monday, February 8, 2016



BY ED SUSMAN

SINGAPORE—Doctors should be alert for opportunistic infections among breast cancer patients undergoing dose dense chemotherapy—especially if those patients are receiving steroids as part of prophylactic control of nausea and vomiting side effects, researchers suggested here.

In a retrospective review, Japanese researchers found that as many as 7 percent of the women treated with dose dense chemotherapy since 2014 have been diagnosed with Pneumocystis jiroveci pneumonia, an opportunistic lung infection often reported among individuals with depressed immune systems.

Study Specifics
In a poster presentation at the ESMO Asia cancer symposium, Jun Masuda, MD, a resident in Medical Oncology at Toranomon Hospital, Tokyo, said, "We should consider reducing steroids used as anti-emetics for chemotherapy and providing P.  jiroveci pneumonia prophylaxis for high-risk patients."

Masuda told OT, "In this study, the incidence of P. jiroveci pneumonia was 7.1 percent among patients treated with dose dense chemotherapy, whereas no P. jiroveci pneumonia was diagnosed among patients treated with a non-dose dense regimen."

The dose dense regimen consisted of doxorubicin 60mg/m2 and cyclophosphamide 600 mg/m2 on day 1 and pegfilgrastim 3.6mg on day 2, every two weeks for four cycles (ddAC). That was then followed by treatment with a taxane, either paclitaxel or docetaxel. The alternative treatment was 5-fluorouracil 500 mg/m2 plus epirubicin 100mg/m2 and cyclophosphamide 500mg/m2 every three weeks for four cycles (FEC), also followed by taxane therapy.

Masuda noted that the finding of P. jiroveci pneumonia in his patients on dose dense chemotherapy is in line with other studies. Nineteen cases with P. jiroveci pneumonia were identified among breast cancer patients treated with AC-containing regimens at Dana-Farber Cancer Institute/Brigham and Women's Hospital from 2000 to 2013, he said.

"Waks AG et al (pubmed/26420402) reported that the risk of Pneumocystis jiroveci pneumonia appeared unique to dose dense chemotherapy," he noted. "Among patients who received ddAC, cumulative incidence of Pneumocystis jiroveci pneumonia was 0.6 percent, while no patients treated with AC in a non-dose-dense schedule developed Pneumocystis jiroveci pneumonia."

Comments
In commenting on the study, Eleonora Teplinsky, MD, a medical oncologist at Northwell Health Cancer Institute, Lake Success, New York, told OT: "Dose-dense AC chemotherapy is routinely used in women receiving neoadjuvant or adjuvant chemotherapy for breast cancer. Dose-dense AC (given every two weeks) improves clinical outcomes significantly when compared to non-dose-dense AC (given every three weeks).

"However," she continued, "it is a highly emetogenic regimen and several drugs, including steroids, are given to patients to minimize nausea/vomiting. Removing steroids from the anti-emetic regimen will worsen toxicities for patients. It is important to recognize the potential side effects of steroids, including Pneumocystis jiroveci pneumonia, especially in high risk patients."

Teplinsky said that dose dense chemotherapy is weight based and steroid guidelines are the same, so it seems unlikely that differences in ethnicity would play a role in development of the opportunistic infection.

Study Participants 
Masuda said the use of dose dense regimens in Japan is a relatively new phenomenon made possible by the approval in his country of pegfilgrastim, a pegylated form of granulocyte colony-stimulating factor approved for prophylaxis of febrile neutropenia in Japan in September 2014. "Since then, ddAC followed by taxane, one of the global standard regimens for early breast cancer, became available," he said.

'We retrospectively reviewed data of consecutive patients with early breast cancer (stage 1-3), who received ddAC-taxane or FEC-taxane as neoadjuvant or adjuvant chemotherapy in our institute between January 2014 and November 2015," he explained. During that time frame, 28 patients were treated with ddAC and 33 were administered FEC.

The median age for the ddAC cohort of women was 46 years; those receiving FEC had a median age of 49 years. All the patients in the study were given a performance status of 0. Almost all the women were diagnosed as having invasive ductal carcinoma. Two women in the ddAC group were diagnosed with invasive lobular carcinoma; one woman in the FEC treated group had invasive lobular carcinoma.

About two-thirds of the patients in each arm of the study were diagnosed with stage 2 breast cancer. About three-fourths of the tumors ranged in size from 2 centimeters to 5 centimeters, the researchers reported.

In the two women who developed P. jiroveci pneumonia, neither had lung comorbidities before starting their breast cancer regimen. A 65-year-old woman developed the opportunistic infection 46 days after beginning chemotherapy. She completed three cycles of chemotherapy. The second patient, a 56-year-old woman, completed four cycles of chemotherapy before contracting pneumonia on day 72, following initiation of chemotherapy. They were both taking about 2 mg/day of dexamethasone as an anti-emetic and both improved on antibiotic therapy.

"Although this retrospective study suggests that ddAC-taxane is feasible in Japanese women with early breast cancer, we need to be careful about the possible development of Pneumocystis jiroveci pneumonia," Dr. Masuda said.


Monday, February 8, 2016

ESMO Asia 2015.jpg 

BY ED SUSMAN

SINGAPORE – Long after surgery to excise endometrial cancer, the disease may—in a small percentage of women—recur, researchers reported here at ESMO Asia 2015.

In a retrospective study that reviewed the outcomes in 2,385 women treated with surgery for endometrial cancer, 22 recurrences occurred after five years, said Akimasa Takahashi, MD, PhD, Assistant Professor of Oncology at the Cancer Institute Hospital for Japanese Foundation for Cancer Research in Tokyo.

In 9 of those 22 cases, the recurrences were more than 10 years after the initial treatment. One patient experienced a recurrence 32.2 years after the initial curative surgery, he said.

Study Specifics
At his poster presentation, Takahashi said that 2,233 of these women seen at the institution between 1970 and December 2009 were treated with curative intent. There were 258 recurrences, but 236 of these recurrences occurred within five years of the initial surgery. The other 22 occurred after that five-year window, he told OT

"We believe patients with endometrioid G1 and G2 cancers should be closely monitored and actively followed for more than five years," he said.

"Three quarters of endometrial cancer patients are confined to the uterus and treated at an early stage," he noted, "but 15 percent to 20 percent recur after primary surgery, generally within three years of primary treatment. The recurrence of endometrial cancer more than five years following surgery for curative resection is a serious concern for patients."

Takahashi said the data for late recurrence is missing in the medical literature, and hence, he and his colleagues attempted to describe the risk and frequency of late recurrence.

Risk of Recurrence
The median age for recurrence was 58 years. Eleven of the patients who recurred—50 percent of these women—were originally diagnosed with Stage 1 disease; three patients were diagnosed with Stage 2 endometrial cancer; and eight other women were diagnosed with Stage 3  cancer. In the multivariate analysis, stage of disease at original presentation was not a factor for risk of recurrence after five years, Takahashi said.

He said there might be a relationship between histology and recurrence. Endometrioid G1 cancer was diagnosed in 11 of the women who recurred; endometrioid G2 cancer was diagnosed in 10 of the women who experienced recurrences; and endometrioid G3 cancer was found in one woman who late had a recurrence.

After surgery, 12 of the women who experienced recurrence had not further therapy. Six of the women who had recurrences underwent post-surgery chemotherapy and four women had post-surgery radiation therapy.

Takahashi said that seven lesions recurred in the lungs, the most common site among the women who had recurrence after five years. There were four recurrences observed in the lymph nodes; three recurrences occurred in the vaginal vault; and eight women experienced recurrences in  multiple areas. Six women with recurrences underwent surgery; 10 had chemotherapy; five had radiotherapy; one patient had hormonal therapy; and seven patients were given best supportive career. Several patients were treated with multiple modalities, the researchers reported.

Treatment
All patients who recurred after 10 years were originally diagnosed with endometrioid G1 cancer. Five of these patients were diagnosed with Stage IA; two women had positive peritoneal cytology; and two were found to have positive lymph nodes.

Among these patients, two were treated with surgery alone; two were treated with surgery plus chemotherapy; one was treated with surgery and radiation; one woman was treated with chemotherapy followed by radiation; two received chemotherapy; and one woman received radiation.  Five of the women were treated surgically; three patients were treated with chemotherapy.

Takahashi said that as far as he has been able to determine, the case series he presented is the largest of its kind to scrutinize late recurrences in endometrial cancer.

Study Comments
In commenting on the study, Jill Whyte, MD, a gynecological oncologist at Northwell Health Cancer Institute in Lake Success, New York, told OT, "As illustrated by this abstract, late recurrence of endometrial cancer—those occurring beyond five years—are extremely rare. These recurrences occurred in fewer than 1 percent of patients undergoing curative intent treatment of endometrial cancer.

"The study showed that the recurrences were almost exclusively in patients with low grade disease and most had not had any therapy beyond initial surgery," she added. "Rather than infer that we are making disease indolent, I think this abstract is showing that the vast majority of patients are, in fact, cured of their disease with initial surgery."


Monday, February 8, 2016

ASCO 16 GU sym logo.jpg 

BY ED SUSMAN

SAN FRANCISCO—A prostate cancer radiation regimen that delivers less radiation over a shorter period of time still provides equivalent oncologic control for low-risk patients as does conventional radiation schemes, researchers reported here at the 2016 Genitourinary Cancers Symposium (Abstract 1).

About 86.3 percent of patients achieved an estimated five-year disease-free survival if they were in the 550-patient cohort receiving a hypofractionated  radiation program that consisted of a cumulative 70 Gray dose delivered in 28 fractions over 5.6 weeks, said W. Robert Lee, MD, Professor of Radiation Oncology at Duke University Medical Center, Durham, North Carolina. Each fraction was 2.5 Gray.

Among the 542 patient receiving the conventional 73.8 Gray in 41 fractions over 8.2 weeks, the estimated disease-free survival at five years was 85.3 percent, Lee reported at his poster presentation. Each fraction was 1.8 Gray.

"The hypofractionated regimen is not inferior to the conventional treatment," he told OT. The difference in outcome in the NRG Oncology RTOG 0415 trial was not statistically significant.

Seeing a Pattern
Other outcomes showed the same pattern:

  • Biochemical recurrence was observed in 8.1 percent (or 50 men in the conventional radiation cohort) and in 6.3 percent (39 men in the hypofractionated group), a non-significant difference.
  • Overall survival at five years was 93.2 percent in the patients treated with the conventional radiation regimen and 92.5 percent in patients who were given the hypofractionated radiation therapy, Lee said. That difference also was not statistically significant.

Median follow-up for the study is 5.9 years, the researchers reported.

"I am using this schedule now but most people are not," Lee said.  "I think that is because our results have not yet been published. I have been using hypofractionated radiation therapy at the Durham VA for seven years."

'Practice Changing' Data
In commenting on the study, Sumanta Pal, MD, Assistant Professor of Medical Oncology at City of Hope, Duarte, Calif., told OT, "In my opinion, this rises to the level of practice changing data. This is Level 1 evidence in the form of a Phase 3 clinical trial that has been done by one of our most respected, cooperative groups in the domain of radiation treatment and it would mandate a change in clinical practice…and perhaps a change in clinical guidelines."

Study Details
To be eligible for the study, patients were required to be diagnosed with histologically confirmed prostate adenocarcinoma within 180 days prior to randomization to either the conventional treatment or the hypofractionated therapy arm. All the patients had Stage 1 to Stage 2c. Their pre-treatment prostate specific antigen (PSA) level had to have been less than 10 ng/mL and the Gleason score of the tumor had to be less than 7. Prior—or planned—androgen deprivation therapy or bilateral orchiectomy was not allowed. They were recruited between April 2006 and December 2009.

About 16 percent of the men in the study receiving the conventional treatment were 59 years of age or less compared with 17 percent of the men who were getting hypofractionated therapy; 44.1 percent of the men receiving conventional therapy were ages 60-69 compared with 45.6 percent of the men who were treated with hypofractionated therapy; and 39.9 percent of men in the conventional cohort were 70 years of age or older, as were 37.1 percent of the men in the hypofractionated therapy group.

Lee reported that 75.8 percent of the patients in the conventional treatment arm of the study were diagnosed with Stage T1 prostate cancer compared, with 80.4 percent of the men in the hypofractionated therapy arm. The remaining patients were diagnosed with Stage 2 prostate cancer. More than 90 percent of the patients were in the Zubrod Performance Status of 0. Only two patients in the study—both in the conventional treatment arm—had Gleason scores less than 4. The others all had scores of 5 or 6.

Late Grade 3 and 4 adverse events were uncommon in the study. Late gastrointestinal Grade 3 adverse events were observed among 2.4 percent of the patients who underwent conventional radiation treatment compared with 4.1 percent of the patients who had hypofractionated radiation therapy. There was one Grade 4 adverse event that occurred to a patient in the conventional treatment arm.

Late genitourinary Grade 3 adverse events were observed among 2.1 percent of the patients in the conventional therapy arm compared with 3.5 percent of men in the hypofractionated radiation therapy group. The only Stage 4 adverse genitourinary event was in the conventional treatment cohort.

Impact of Results
"Rectal bleeding is what is driving the Grade 2 and Grade 3 adverse events in this study," Lee noted. "The rating scales in this area are not that great. They say 'mild' or 'moderate' but there is not good definition of what is meant."

Grade 3 bleeding events required some interventions, he said. Grade 2 adverse events—also mainly reported rectal bleeding—were seen in as many as 20 percent of patients on conventional treatment and in 26 percent of those patients who received the short course of radiation.

"A lot of the Grade 2 rectal bleeding was occasional spotting," he said, but those cases did not require interventions.

"The benefit of this demonstration is that we shorten the duration of therapy by more than two weeks," said Pal. "And that may relieve many burdens, including economic costs and time costs to the patient. One of the traditional challenges with radiation therapy in prostate cancer is that it is administered over such an extended period of time. It becomes a real challenge for patients who come from long distances for their radiation treatment and certainly might compromise compliance."

Lee said his patients have been very accepting of the shorter course of therapy. "When you present the two regimens to a patient, very few of them select the longer treatment option," he said.

The conference is co-sponsored by the American Society of Clinical Oncology,  American Society for Radiation Oncology and Society of Urologic Oncology.


Wednesday, January 27, 2016

ASCO 16 GI Sym logo WEB.jpg
 

BY ROBERT H. CARLSON

Results from a Phase III Polish study point to a potential new standard of treatment for patients with advanced rectal cancer, short-course chemoradiation. Patients in the Polish II trial who received five days of neoadjuvant radiation followed by consolidation chemotherapy saw a statistically significant improvement in three-year overall survival compared with patients treated with standard five-week chemoradiation. Results of the multicenter, Phase III study were presented at the Gastrointestinal Cancer Symposium 2016 (Abstract 489).

The study compared neoadjuvant 5x5 Gy and consolidation chemotherapy versus standard preoperative chemoradiation in “unresectable” fixed cT3 cancer with limited movability, or cT4 rectal cancer with threatened resection margin. None had distant metastases.

The experimental treatment resulted in a higher radical resection (R0) rate, the primary study endpoint, and also higher pathological complete response, although the differences were not statistically significant.

And while three-year overall survival was greater for the experimental group, disease-free survival and the cumulative incidence of local failure were not statistically different between the two groups.

But there was a trend toward lower toxicity and lower cost, as well as greater convenience in the experimental arm of the study, the researchers reported.

“The new regimen has similar efficacy but causes fewer side effects and is more convenient for patients. It is also less costly compared to standard chemoradiation, so it may be especially valuable in limited-resource settings,” said first author Lucjan Wyrwicz, MD, PhD, Professor and Chief, Medical Oncology Unit, Department of Gastrointestinal Cancer, Maria Sklodowska-Curie Memorial Cancer Centre, Warsaw, Poland, who spoke on behalf of the Polish Colorectal Study Group. Principal investigator is Krzysztof Bujko, MD, PhD.

In a presscast held ahead of the symposium, Wyrwicz said two earlier studies had shown that chemoradiation is of equal efficacy to short course radiotherapy in patients with resectable rectal cancer T3N0-2M0 tumors – Polish I (Br J Surg2006;93:1216-23) and the Trans Tasman trial (J Clin Oncol2012;30:3827-33). This new report includes patients with more advanced disease, he pointed out.

The trial included 515 patients recruited in Poland and randomly assigned to the experimental group for a short course of five days of radiotherapy at 5 Gy per day followed by three courses of FOLFOX4 delivered over two days per week in weeks 3, 5, and 7 (261 patients); or to a control group receiving 50.4 Gy delivered in 28 fractions given simultaneously with a regimen of 5-Fu bolus, leucovorin and oxaliplatin (254 patients).

Oxaliplatin use was at the discretion of the patient's physician. By study end, 70 percent of patients had received oxaliplatin. Both groups underwent surgery approximately 12 weeks after starting radiation and six weeks after neoadjuvant chemotherapy.

Wyrwicz said acute toxicity rates were lower in the experimental group compared with controls (74% versus 83%). The major toxicities associated with radiotherapy include inflammation of the rectum, diarrhea, inflammation of the bladder, and local skin radiation response. The rate of patients with grade 3/4 toxicity was identical in the two groups, at 24 percent.

Improved Radical Resection Rate
The primary endpoint, rate of resections with negative margins (R0), was 77 percent in the experimental group versus 71 percent in the control group. Pathological complete response rates were 16 percent versus 11.5 percent, respectively.

With a median follow-up of 35 months, three-year overall survival for the experimental group was 73 percent versus 65 percent for controls; disease-free survival rates were almost identical at 53 percent and 52 percent, respectively; and the cumulative incidence of local failure was 22 percent in the experimental group and 21 percent in the controls.

Wyrwicz said short-course radiotherapy may be a particularly helpful option for patients with advanced rectal cancer with metastases in liver or lungs who are potential candidates to have all sites of disease resected.

“A shorter duration of radiotherapy allows such patients to start chemotherapy to control metastases much earlier,” Wyrwicz said. "This seems to be feasible and also effective in this rare subgroup of patients.”

The study was funded by the Polish Ministry of Science and Higher Education.

Oxaliplatin Not Standard
Smitha Krishnamurthi, MD, an ASCO spokesperson and moderator of the presscast, said the short course of radiation is more popular in the Europe than in the U.S., “but these results may lead to increased usage of this method of radiation.

“However, we must keep in mind that chemoradiation in this trial included oxaliplatin, which is not a standard treatment and has been shown to increase toxicity of the regimen,” said Krishnamurthi, Associate Professor in the Department of Medicine-Hematology and Oncology at Case Western Reserve University School of Medicine and leader of the Gastrointestinal Oncology Disease team.

“There were several randomized trials that started before this Polish study started that asked the question, ‘what is the value of adding oxaliplatin to 5-Fu and radiation therapy as adjuvant therapy for rectal cancer?’ and they found it did not increase the efficacy of the radiation but did increase toxicity,” she said. “That's why, when those results came out, the [Polish II] study we discussed today gave participants the option of eliminating the oxaliplatin.”

Wyrwicz explained that the patients in his study were advanced cases with what would have been considered unresectable if surgery were done first.

“At the time the trial started, adding extra chemotherapy sounded reasonable since the aim was to maximize the efficacy of the experimental arm,” he said. “But looking back to the start of this trial, I would not have included oxaliplatin because of the toxicity.”

‘A Lot of Interest’
The study is nonetheless relevant, Krishnamurthi said, since it may be the first study to show the short-course radiation achieving a reduction in tumor. That may have been due to the use of chemotherapy afterward radiotherapy, she said, but could also be due to the delay in surgery, allowing time for the tumor to shrink.

“There is a lot of interest in incorporating short-course radiation because of its convenience and less expense in treatment of rectal cancer, and some randomized trials of short-course radiotherapy are ongoing that will provide us with more data.”

The Gastrointestinal Cancers Symposium 2016 is sponsored by the American Gastroenterological Association Institute, American Society for Radiation Oncology, American Society of Clinical Oncology, and Society of Surgical Oncology.
 


Wednesday, January 27, 2016

 

BY ROBERT H. CARLSON

The radioisotope 177Lu-DOTATATE (Lutathera) has a favorable safety profile with no clinically relevant adverse effects in treatment of patients with midgut neuroendocrine tumors (NETs) who have progressed on somatostatin analogue treatment, according to new data from the phase III NETTER-1 trial.

The data were discussed at a presscast in advance of the Gastrointestinal Cancer Symposium 2016 (Abstract 194).

NETTER-1 Trial
NETTER-1 is a multicenter, randomized, placebo-controlled trial that compared Lutathera with Ocreotide LAR in patients with inoperable, progressive, somatostatin-receptor positive midgut NETs.


In the first report from NETTER-1, presented at the 2015 European Cancer Congress (ECC) meeting in Vienna, Austria, patients treated with the experimental drug had a 79 percent lower risk of disease progression or death compared with those treated with Octreotide LAR.

“Currently, there are limited therapeutic options for patients with advanced midgut neuroendocrine tumors progressing on first-line somatostatin analog therapy,” said study author Jonathan R. Strosberg, MD, Associate Professor at the H. Lee Moffitt Cancer Center, in the presscast previewing the symposium. “Midgut NET is highly resistant to systemic therapy and Lutathera has a major therapeutic benefit for this patient population.”

Lutathera is a peptide receptor radionuclide that targets somatostatin receptors, which are overexpressed in approximately 80 percent of NETs, to deliver cytotoxic radiation directly to the tumor, Strosberg said.

At this meeting, Strosberg reported in greater detail on adverse events in NETTER-1. Overall, he said, the numbers of adverse events, including serious side effects, were similar between the two treatment groups (see "Adverse Events" below).

The NETTER-1 data are on 230 patients with Grade 1-2 metastatic midgut NETs who were randomly assigned to receive treatment with Lutathera every eight weeks for four cycles (115 patients), or the somatostatin analogue Octreotide LAR 60 mg every four weeks (115 patients). Octreotide LAR is the current standard of care for GI NETs.

Patients in the control arm had progressed on Ocreotide LAR 30 mg, the label use.

Each Lutathera treatment dose was 7.4 GBq (gigabecquerels), equal to 200 millicurie.

At the time of statistical analysis, the number of confirmed disease progressions or deaths was 23 in the Lutathera group and 67 in the Octreotide LAR 60 mg group, Strosberg said. The study also suggested that Lutathera may extend patient survival: there were 13 deaths in the Lutathera group versus 22 with standard care.

“This is the first interim look at overall survival and not statistically significant at this point, but it does suggest an overall survival advantage for Lutathera,” Strosberg said.

At the time of the report, median PFS had not been reached for Lutathera, and was 8.4 months with Octreotide LAR.

Responses
Among 201 patients currently evaluable for tumor response, there were 19 (18.8%) complete and partial responses in the Lutathera group—1 CR and 17 PRs—versus three (3.0%, 3 PRs) in the Octreotide LAR 60 mg group.

This study received funding from Advanced Accelerator Applications (AAA), the maker of Lutetium.

‘Impressive Ability’
In April 2015, the FDA granted Fast Track designation to Lutathera for the treatment of patients with inoperable, progressive, well-differentiated, somatostatin-positive carcinoid tumors of the midgut.
Smitha Krishnamurthi, MD, an ASCO spokesperson and moderator of the presscast, said Lutathera showed impressive ability to slow the growth of midgut NETs that have progressed on somatostatin analogue therapy.

“Also notable was the Lutathera response rate of 18 percent in tumors which are typically unresponsive to systemic therapy,” said Krishnamurthi, Associate Professor in the Department of Medicine-Hematology and Oncology at Case Western Reserve University School of Medicine and leader of the Gastrointestinal Oncology Disease team.


Adverse Events
Adverse events with Lutathera versus Ocreotide LAR, respectively:
· nausea all grades: 59 percent versus 12 percent;
· nausea grade-3/4: 4 percent versus 2 percent;
· vomiting all grades: 47 percent versus 10 percent;
· vomiting grade-3/4: 7 percent versus 0 percent;
· diarrhea all grades: 29 percent versus 19 percent;
· diarrhea grade-3/4: 3 percent versus 2 percent;
· thrombocytopenia all grades: 25 percent versus 1 percent;
· thrombocytopenia grade-3/4: 2 percent versus 0 percent;
· anemia all grades: 14 percent versus 5 percent;
· anemia grade-3/4: 0 percent versus 0 percent;
· lymphopenia all grades: 18 percent versus 2 percent; and
· lymphopenia grade-3/4: 9 percent versus 0 percent.

 

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