Conor Killmurray

The overall health-related quality of life (HRQoL) among younger patients with colorectal cancer (CRC) is poorer as incidence in patients under the age of 50 increases, with social and functional well-being suffering more with longer treatment durations, according to data presented during the 2021 ASCO Gastrointestinal Cancers Symposium.

Using the Functional Assessment of Cancer Therapy (FACT-C) survey, which assesses HRQoL globally, along with a cross-sectional online survey for a CRC-specific scale that looked at emotional, physical, social, and functional well-being domains, researchers evaluated the responses of 235 patients with CRC and found an overall low score of HRQoL of 67.3 out of a possible 136 in this patient population.

The mean age of the sample was 33.76 years old and the location of the patients’ tumors were either in the colon (41.7%) or rectum (58.3%). The majority of patients (33.23%) were diagnosed with stage 2 cancer and 98% were non-metastatic, while 42% experienced relapse of their disease. One hundred and eighty-nine patients (61.4%) were 6-18 months from their diagnosis or relapse, but key demographic figures like age and ethnicity did not have a significant statistical difference between the two groups.

Patients were split into two categories of 6-18 months from their initial diagnosis or relapse, and 19-36 months from diagnosis or relapse. While researchers did not find a significant difference between the two groups in terms of emotional and physical well-being, scores were low across all domains, with social well-being the highest (15.15/28) and emotional well-being the lowest (11.44/24). Moreover, functional well-being rated close to the bottom (11.84/28), with physical well-being the second highest (15.15/28).

Higher scores for physical and emotional well-being were observed in patients who had a longer time between diagnosis compared to short-term, whereas significantly lower scores were observed in social well-being for patients who had a shorter time between their diagnosis and the survey, at 15.24/28 versus 14/28 respectively (

 <0.01). This was also observed in functional well-being, which scored at 13.20 for the 6-18 month group versus 11.12 for 19-36 month group (

The researchers concluded that with the overall low HRQoL scores for young CRC survivors in the categories of social and functional well-being should be targeted by appropriate methods, as they were the lowest. These methods would include counseling and quality of life interventions, but further study into which of these methods would be best is needed.

Ann Miller K, Stal J, Gallagher P et al. Health-related quality of life and time from diagnosis among young adult colorectal cancer survivors. Presented at: American Society of Clinical Oncology Gastrointestinal Cancers Symposium. Abstract 34.

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The overall health-related quality of life among younger patients with colorectal cancer is poorer as incidence in patients under the age of 50 increases, with social and functional well-being suffering more with longer treatment durations.

Health-Related Quality of Life Low in Younger Colorectal Cancer Survivors

Using 5- HT3 inhibitors and early intervention with loperamide was shown to manage gastrointestinal (GI) adverse events (AEs) oral paclitaxel and encequidar in patients with metastatic breast cancer, according to a study presented during the San Antonio Breast Cancer Symposium.

This combination regimen allows for fewer AEs, but investigators looked to find a way to prevent GI AEs that were found to be higher following treatment with oral paclitaxel and encequidar.

“Paclitaxel is substrate of the intestinal e-flux pump p-glycoprotein that leads to low oral bioavailbailty. Encequidar is a specific p-glycoprotein absorbed by patients to help bioavailbailty,” explained lead investigator Hope Rugo, MD, from the University California San Francisco Helen Diller Family Comprehensive Cancer Center, in a poster presentation at SABCS. “This avoids the need for Cremophor risk and allows for at home dosing with patients and eliminates the need for IV infusions.” However, she added, the incidence of gastrointestinal adverse events from this combination was high.

The researchers investigated preventive measures for GI AEs associated with oral paclitaxel and encequidar or IV paclitaxel – which were evaluated in a multinational trial looking at the safety of this combination in 442 patients.

Patients were randomized 2:1 on either oral paclitaxel and encequidar (205mg/m2/day x3 weekly) or IV paclitaxel (175 mg/m2 every three weeks) until disease progression or toxicity. The primary end point of the study was efficacy as defined by tumor response with secondary endvpoints of progression-free survival (PFS) and overall survival (OS).

All patients on IV paclitaxel (n = 111) were given dexamethasone and antihistamine premedication and after 30% (n = 70) of patients were enrolled to include those on oral paclitaxel and encequidar the protocol was amended to address the imbalance of GI AEs. Treatments included loperamide taken at home at the onset of diarrhea along with prophylactic anti-emetic therapy.

The most frequently prescribed anti-emetic therapies included ondanesteron, granisetron, palenosetron, aprepitant, metoclopramide, domperidone, and aprepitant. The majority of patients in the combination (59%) and monotherapy (54%) arms received ondanesteron.

After the amended use of prophylactic anti-emetic therapy, there was a marked decrease of grade 2 or higher vomiting and diarrhea in patients on oral paclitaxel and encequidar, from 24% to 7% and 27% to 16% respectively. A greater incidence of both AEs were seen in patients treated with IV paclitaxel.

Of note, prior to the amendment, overall GI AEs occurred less frequently in patients on IV paclitaxel compared to the combination regimen, with a rate of only 1% of grade 3 vomiting and diarrhea occurring. Grade 3 incidences prior to the amended treatment in patients on the oral regimen were 7% in vomiting and 9% in diarrhea, showing a slight decrease to 4% and 3%, respectively.

Rugo H, Umanzor G, Barrios F J et al. Oral paclitaxel and encequidar (oPac+E) in the treatment of metastatic breast cancer (mBC): management of gastrointestinal adverse events (GI AE). Presented at: 2020 San Antonio Breast Cancer Symposium; December 8-11, 2020; Virtual.

Using 5- HT3 inhibitors and early intervention with loperamide was shown to manage gastrointestinal adverse events oral paclitaxel and encequidar in patients with metastatic breast cancer, according to a study presented during the San Antonio Breast Cancer Symposium.

Antiematics and Loperamide Resolve GI AEs Related to Oral Paclitaxel Plus Encequidar in mBC

Chimeric antigen receptor (CAR) T-cell therapy with lisocabtagene maraleucel (liso-cel) led to rapid and durable responses in patients with high-risk relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL). Updated results of the ongoing TRANSCEND CLL 004 study (NCT033311980) also showed that a high degree of undetectable minimal residual disease (uMRD) was achieved, according to findings presented at the 2020 ASH Annual Meeting.

The phase 1/2 trial examining liso-cel, the investigational, CD-19 directed, defined composition, 4-1BB CAR T-cell product, enrolled a total of 23 patients with R/R CLL or SLL. All were evaluable for safety, while 22 were evaluable for efficacy. The median age was 66 years, all patients had undergone a median of 6 prior therapies, and 83% of patients had high-risk disease. All 23 patients had previously received ibrutinib (Imbruvica). Ninety one percent (n= 21) patients were refractory to, or relapsed on, ibrutinib and 9% (2) were intolerant to ibrutinib. Forty eight percent (n= 11) were refractory to both a prior BTK inhibitor and venetoclax (Venclexta).

Clinicians administered the liso-cel treatment after 3 days of lymphodepletion with fludarabine and cyclophosphamide, at one of two dose levels: 50 × 106 (DL1) or 100 × 106 (DL2) CAR+ T cells. Treatment with liso-cel produced an overall response rate (ORR) of 82% (n= 18) with a complete response rate of 45% (n= 10).

At the 15-month follow up and the 18-month follow up, researchers found responses were maintained at 53% (n=10/19; 6 CRs) and 50% (n=7/14; 5 CRs) respectively. However, at a median follow up of 18 months, the median duration of response was not reached in patients who had initially responded to liso-cel, and median progression-free survival (PFS) was 18 months.

“For patients who had failed both BTK inhibition and venetoclax prior to enrolling onto our study, the baseline disease characteristics of those 11 patients were fairly similar to the monotherapy total cohort of 23 patients,” explained lead author Tanya Siddiqi, MD, in a presentation at ASH.

MRD was assessed in the patient’s blood by flow cytometry, with 20 of the 23 patients being MRD evaluable. Fifteen patients had uMRD in the blood while 13 had uMRD in their bone marrow. Sixty percent of patients achieved uMRD by day 30 of treatment with liso-cel.

Siddiqi, a hematologist oncologist at the City of Hope, went on to note that lico-cel therapy elicited rapid, deep and durable responses and highlighted how, after a 24-month follow up, all 7 patients who completed the 2-year study maintained their response.

“These responses appear to be durable over time. At the 12-month mark, 50% of patients were in response and only 2 of these responders progressed beyond the 12-month mark,” Siddiqi said in her presentation.

Additionally, researchers found the safety profile of liso-cel to be in line with that previously reported, with no late or delayed adverse events emerging during the 2-year follow-up. The most common treatment emergent adverse events (TAEAs) were grade 3/4 and included thrombocytopenia (70%, n= 16), anemia (78%, n= 18), neutropenia (57%, n- 13), and leukopenia (43%, n= 10).

Overall, patients in this heavily pretreated, high-risk population who were treated with liso-cel had a high rate of uMRD, which was even seen in patients who were refractory to both a BTK inhibitor and venetoclax.

Siddiqui concluded by noting that the phase 2 monotherapy expansion of the TRANSCEND CLL 004 study is currently enrolling.

Siddiqi T, Soumerai J, Dorritie K, et al. Updated Follow-up of Patients with Relapsed/Refractory Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma Treated with Lisocabtagene Maraleucel in the Phase 1 Monotherapy Cohort of Transcend CLL 004, Including High-Risk and Ibrutinib-Treated Patients. Presented at: 2020 ASH Annual Meeting & Exposition. Abstract 546.

Chimeric antigen receptor T-cell therapy with lisocabtagene maraleucel led to rapid and durable responses in patients with high-risk relapsed/refractory chronic lymphocytic leukemia or small lymphocytic lymphoma. 

Liso-Cel Achieves High MRD Negativity Rate in High-Risk CLL/SLL

The health-related quality of life (HRQoL) had clinically meaningful improvements with pembrolizumab (Keytruda) as a first-line therapy for patients with microsatellite instability-high and/or mismatch repair-deficient metastatic colorectal cancer versus standard-of-care (SOC) chemotherapy, according to new data presented at the ESMO Virtual Congress 2020.

Pembrolizumab (Keytruda) as a first-line treatment demonstrated clinically meaningful improvements in the health-related quality of life (HRQoL) of patients with microsatellite instability-high and/or mismatch repair-deficient metastatic colorectal cancer compared with standard-of-care (SOC) chemotherapy, according to new research presented at the European Society for Medical Oncology (ESMO) Virtual Congress 2020.

The Phase III KEYNOTE-177 study analyzed 294 treatment-naïve U.S. patients with microsatellite instability-high (MSI-H) and/or mismatch repair-deficient (dMMR) metastatic colorectal cancer (mCRC). In that study, researchers demonstrated that, in comparison to chemotherapy (mFOLFOX6 or FOLFIRI) with or without bevacizumab or cetuximab, pembrolizumab alone provided superior progression-free survival (PFS). In the current analysis, the investigators found that immunotherapy sparked an increase in HRQoL over 2 years compared with chemotherapy.

Patients were randomized 1:1 to take either pembrolizumab (n=152) or SOC chemotherapy (n=142) with or without bevacizumab or cetuximab. In a follow-up at 18 weeks, clinically meaningful improvement was found based on the results of 2 validated, self-reported questionnaires, measuring against a baseline score of 0. The QLQ-C30 global health status quality-of-life scale found a least-squares mean (LSM) score change of 8.96 (95% CI, 4.24-13.69; 

= .0002) and the EQ-5D VAS demonstrated an LSM increase of 7.38 (95% CI, 2.82-11.93; 

= .0016) for patients receiving pembrolizumab compared with chemotherapy. According to data presented at the ESMO virtual congress, during the time period 18-45 weeks after the start of treatment, the LSM score for patients receiving pembrolizumab improved by another 5-10 points, while the score for those taking chemotherapy dropped by several points.

Another questionnaire, QLQ-CR29, showed that patients taking pembrolizumab reported improvements in anxiety, weight and, for men, sexual interest between baseline and week 18; patients taking chemotherapy also saw an improvement in anxiety but reported declines in body image and, among men, sexual interest. Sexual interest dropped for women on both regimens.

Moreover, time to deterioration, including physical and social functioning and fatigue, was delayed in patients who received pembrolizumab versus chemotherapy (HR, 0.50; 95% CI, 0.32-0.81; P=0.0016). For instance, in looking at the probability of no physical deterioration during

that period, researchers noted 29 documented events in patients taking pembrolizumab compared with 45 events for patients taking chemotherapy.

Adverse effects such as urinary frequency, abdominal pain, bloating and stoma care problems improved over time with pembrolizumab, while issues including buttock pain, dry mouth, alopecia, taste alterations and sore skin increased with chemotherapy.

These data provide further proof that pembrolizumab monotherapy is a viable treatment for patients with MSI-H and/or dMMR mCRC in the first-line setting, Thierry André, MD, the study’s lead author, said in an oral presentation at the virtual conference. Andre, head of the Medical Oncology Department at the Saint Antoine Hospital, Assistance Publique Hôpitaux de Paris, emphasized that meaningful improvements in quality of life were seen with pembrolizumab but not with chemotherapy, adding that further study is warranted. André did caution that results were limited to the treatment period, and while this immunotherapy works well, especially in the PD-L1 pathway, its usefulness can be limited depending on whether a patient’s disease is resistant to treatment.

“These findings further support use of pembrolizumab as a standard of care for first-line treatment of patients with MSI-H/dMMR mCRC,” André concluded.

Andre T, Amonkar M, Norquist J, et al. Health-related quality of life (HRQoL) in patients (pts) treated with pembrolizumab (pembro) vs chemotherapy as first-line treatment in microsatellite instability-high (MSI-H) and/or deficient mismatch repair (dMMR) metastatic colorectal cancer (mCRC): Phase III KEYNOTE-177 study. Presented at: European Society of Medical Oncology Virtual Congress 2020; September 19- 21, 2020; Virtual. Abstract 396O.

The health-related quality of life had clinically meaningful improvements with pembrolizumab as a first-line therapy for patients with microsatellite instability-high and/or mismatch repair-deficient metastatic colorectal cancer versus standard-of-care chemotherapy, according to new data presented at the ESMO Virtual Congress 2020.

Conor Killmurray | Authors

Articles

Health-Related Quality of Life Low in Younger Colorectal Cancer Survivors

Antiematics and Loperamide Resolve GI AEs Related to Oral Paclitaxel Plus Encequidar in mBC

Liso-Cel Achieves High MRD Negativity Rate in High-Risk CLL/SLL

Improvements Seen in Health-Related QoL With First Line Pembrolizumab for DNA Repair-Deficient Metastatic CRC