Chemotalk Newsletter

Chemotalk Newsletter, Vol. 117 February 1, 2018

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February's news begins with...

MANY ELDERLY LUNG CANCER PATIENTS RECEIVE NO TREATMENT

By Mark L. Fuerst

Nearly two-thirds of older patients with stage III LUNG CANCER do not receive any treatment, according to a new study.

Although more than one-third of new lung cancers are diagnosed in patients age 75 years and older, elderly patients may not receive standard-of-care therapy for lung cancer‹concurrent chemotherapy and radiation‹due to their age, concerns about fragility, less willingness of patients to pursue aggressive therapy, or concerns over the usefulness of therapy for patients with competing risk factors.

To gain insights into how octogenarian and nonagenarian patients are treated and how they fare, researchers led by Richard J. Cassidy, MD, of the Winship Cancer Institute at Emory University in Atlanta, examined data on US patients age 80 years and older with stage III non­small-cell lung cancer from 2004 to 2013 who had complete treatment records available in the National Cancer Data Base (NCDB). The main goal of the study was to identify patient and tumor factors associated with receiving or not receiving standard therapy. The results were published in Cancer.

Of the total 12,641 patients (median age, 83 years) entered in the study, 7,921 (62.7%) received no therapy. Black race and living in a lower-educated census tract were linked with a 23% and 20% increased likelihood of not receiving care, respectively, while treatment at an academic center was associated with a 20% increased likelihood of receiving cancer-directed therapy. Male sex and improved comorbidity status were also associated with receiving some form of therapy.

Patients who received no treatment or only radiation were more likely to die during the years analyzed than those receiving the standard-of-care therapy.

"Our study is the largest to look at patients 80 years and older with stage III lung cancer. We highlight risks for patients not receiving standard therapy and show that patients who receive standard care live longer," said Cassidy. "Our study also highlights healthcare disparities in the oncology community and showcases a need for the oncology community to address. This may provide information to guide outreach programs to engage the elderly community in seeking appropriate therapy for stage III lung cancer."

The overall survival benefit was confirmed after balancing for other demographic, socioeconomic, and disease variables. This suggests that the value of standard therapy is independent of age, race, comorbidity status, histology, or treatment facility.

Because of concerns about aggressive chemoradiation, targeted agents and immunotherapy may play a role in the treatment of elderly lung cancer patients. Ongoing clinical trials are examining the impact of targeted agents and immunotherapy in the upfront, nonmetastatic setting. These agents would be useful in an elderly population because their side effect profiles are generally more favorable than traditional chemotherapy, the researchers noted.

The "most alarming finding," the researchers wrote, was that a significant percentage of patients received no therapy at all.

They noted that the NCDB captures about 70% of new cancer diagnoses and includes many community centers; therefore, the study¹s population represents the cancer community at large.

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COMPETE RESPONSES CAN ENDURE POST PEMBROLIZUMAB IN METASTATIC MELANOMA

By Dave Levitan

Patients with METASTATIC MELANOMA who are treated with pembrolizumab and achieve a complete response (CR) can maintain those responses for an extended period, even after discontinuation of the therapy, according to a new study.

The immune checkpoint inhibitor pembrolizumab has offered a promising new treatment option in metastatic melanoma, a malignancy with an historically poor median overall survival. Data remain limited, however, on potential predictors of CR with pembrolizumab and on patient disposition following treatment discontinuation.

Researchers led by Caroline Robert, MD, PhD, of Institut Gustave Roussy in Paris, examined baseline characteristics and long-term follow-up of patients treated in the KEYNOTE-001 study. Of 655 total treated patients, 105 achieved a CR (16.0%), after a median follow-up of 43 months. Results of the analysis were published in the Journal of Clinical Oncology.

Of the 105 patients with a confirmed CR, 92 of them (87.6%) remained in CR after a median of 30 months. Fourteen patients (13.3%) were still receiving pembrolizumab treatment for a median of at least 40 months.

Of the 91 patients who stopped pembrolizumab therapy after a CR, 67 elected to stop treatment (63.8%) and proceeded to observation without further anticancer therapy. The median time to CR among these patients was 13 months, and the median duration of pembrolizumab therapy was 23 months.

Two of those who proceeded to observation died of causes unrelated to treatment or disease (cardiac failure and aspiration), and four (6.0%) had progressive disease 5.6, 8.5, 22.8, and 37.3 months, respectively, after discontinuing pembrolizumab. Three of them began a second course of pembrolizumab; one had progressive disease after 4 months and remains alive, one continued to receive therapy after approximately 15 months, and one received the drug for 9 months before dying as a result of a malignant neoplasm progression.

In total, only 7 of the 105 patients with a CR had confirmed progressive disease. The 24-month disease-free survival rate from the declaration of CR was 90.9%; among the 67 patients who discontinued the therapy and moved on to observation, the 24-month disease-free survival rate was 89.9%.

An analysis found that baseline tumor size and PD-L1 status were relevant predictors of response in the cohort. Patients with larger tumors (5 to 90 cm) had a lower CR rate, with the exception of those with 5- to 10-cm tumors with positive PD-L1 expression. The highest rate of CR was seen in patients with small tumors who were PD-L1­positive; these patients had a CR rate of 42.7%.

"The goal now is to understand the mechanisms underlying such optimal responses to therapy and the reasons for primary or secondary resistance in patients who do not experience CR," the authors wrote. "Additional studies are needed to evaluate the optimum duration of treatment to achieve prolonged CR, determine when to stop treatment after CR, and assess the interplay of the various factors potentially associated with CR."

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OBSERVED SMALL PAPILLARY CARCINOMAS UNLIKELY TO GROW IN FIRST 5 YEARS

By Leah Lawrence

Only a small percentage of patients undergoing active surveillance for PAPILLARY THYROID CARCINOMA (PTC) will experience increases in tumor diameter by 3 mm or more during the first 5 years of surveillance, according to the results of a study published in JAMA Otolaryngology­Head & Neck Surgery.

The study described the kinetics of PTC tumor growth in a cohort of 291 patients undergoing active surveillance for low-risk disease using serial tumor measurements via ultrasonography.

"As the number of small, incidentally detected PTCs continues to increase, new approaches are needed to avoid overtreatment of tumors that would otherwise remain indolent and asymptomatic while identifying the small percentage of such tumors that will continue to grow," wrote researcher R.
Michael Tuttle, MD, of Memorial Sloan Kettering Cancer Center in New York, and colleagues. "Because PTCs appear to follow predictable growth kinetics under active surveillance, serial measurements of tumor volume hold significant promise in triaging patients to observation vs surgery."

Patients in the study were followed for a median of 25 months. The majority of patients had tumors that were 1 cm or smaller (79.7%). Less than 5% of patients were considered to be ideal candidates for observation, meeting requirements that included age greater than 60 years and solitary papillary microcarcinoma within an otherwise normal thyroid gland. However, most patients were considered appropriate for observation.

During follow-up, 3.8% of patients had a tumor diameter growth of 3 mm or more. The cumulative incidence of growth of 3 mm or more was 2.5% at 2 years and 12.1% at 5 years. The cumulative incidence of volume increase greater than 50% was 11.5% at 2 years and 24.8% at 5 years. No regional or distant metastases developed during active surveillance.

The researchers found that a younger age at diagnosis (hazard ratio [HR] per year, 0.92; 95% CI, 0.87­0.98; P = .006) and risk category (HR for inappropriate, 55.17; 95% CI, 9.40­323.19; P < .001) were independently associated with the likelihood of a 3-mm growth in diameter.

In addition, patients aged 50 or younger had almost five times the risk for experiencing tumor growth compared with patients older than 50 (27.3% vs 4.6%; P = .03).

"There is little doubt that the success of our active surveillance management program depends on the availability of specialized and highly skilled radiologists who are an integral part of our thyroid cancer disease management team," the researchers wrote.

In an editorial published with the study, Joseph Scharpf, MD, of the Cleveland Clinic Foundation in Ohio, called the data from this study invaluable in its support of active surveillance protocols in the United States.

"Arguably, some may offer the concern that potentially all tumors may start at a very small size, yet there are patients who continue to die of thyroid cancer. Tumor growth, either in 1 dimension or by volume, may be too rudimentary of a marker to provide the comfort level ultimately desired for a lifetime of active surveillance for all patients," Scharpf wrote. "Further discovery of new prognostic and predictive markers to guide personalized care will hopefully result in better results and a decrease in potential overtreatment."

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TRIPLET THERAPY FOR FOLLICULARLYMPHOMA ASSOCIATED WITH SERIOUS

By Bryant Furlow

Treatment of previously untreated FOLLICULAR LYMPHOMA with atezolizumab checkpoint-inhibition immunotherapy combined with obinutuzumab and bendamustine was associated with widespread adverse events and a treatment-related death, according to an interim analysis of a phase Ib/II cohort study (abstract 481) presented at the 59th American Society of Hematology Annual Meeting and Exposition, held last month in Atlanta.

 

Toxicity was largely manageable, however, reported lead study author Anas Younes, MD, of the Memorial Sloan Kettering Cancer Center in New York.

Atezolizumab is a fully-humanized, engineered IgG1 monoclonal antibody that targets programmed death ligand 1 (PD-L1). Obinutuzumab is a humanized
anti-CD20 monoclonal antibody. Of 42 patients with grade 1, 2, or 3a follicular lymphoma who were enrolled in the study, 40 had not previously received treatment for their disease. Two patients who had experienced relapsed/refractory follicular lymphoma participated only in the study¹s safety run-in phase, along with four previously untreated patients, prior to main enrollment. The safety run-in phase involved intensive safety monitoring, Younes said.

The study involved a 6-month induction period and 2-year maintenance period. Induction involved 28-day treatment cycles with infusions of obinutuzumab (1000 mg on days 1, 8, and 15 of cycle 1 and day 1 of cycles 2­6), bendamustine (90 mg/m2 on days 1 and 2 of cycles 1­6) and atezolizumab (840 mg on days 1 and 15 of cycles 2­6). Patients achieving partial or complete response then underwent maintenance therapy with obinutuzumab (1000 mg on day 1 of every other month) and atezolizumab (840 mg on days 1 and 2 each month) for up to 24 months. It is too early to say how durable the reported responses will be, Younes cautioned.

The primary study endpoint was PET/CT-assessed response at the end of induction by an independent review committee.

Two patients died during the study. One patient¹s death was deemed to have been treatment-unrelated. The other, however, which occurred after the data cutoff date, was caused by atezolizumab-related cardiac arrest following grade 4‹probably immune-mediated‹myocarditis and bronchiolitis obliterans.

All patients experienced at least one adverse event, prompting bendamustine dose reductions, treatment interruptions, and discontinuations. The most common treatment-related grade 3/4 toxicities were neutropenia and thrombocytopenia. The most frequent treatment-related serious adverse event was atezolizumab-related infusion-related reactions.

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And if you have any thoughts of how this newsletter could be improved, please email me directly, at Elaine@elainejesmer.com.

Elaine Jesmer

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