Busyamas Chewaskulyong

Gefitinib or Carboplatin–Paclitaxel in Pulmonary Adenocarcinoma

BACKGROUND Previous, uncontrolled studies have suggested that first-line treatment with gefitinib would be efficacious in selected patients with non-small-cell lung cancer. METHODS In this phase 3, open-label study, we randomly assigned previously untreated patients in East Asia who had advanced pulmonary adenocarcinoma and who were nonsmokers or former light smokers to receive gefitinib (250 mg per day) (609 patients) or carboplatin (at a dose calculated to produce an area under the curve of 5 or 6 mg per milliliter per minute) plus paclitaxel (200 mg per square meter of body-surface area) (608 patients). The primary end point was progression-free survival. RESULTS The 12-month rates of progression-free survival were 24.9% with gefitinib and 6.7% with carboplatin-paclitaxel. The study met its primary objective of showing the noninferiority of gefitinib and also showed its superiority, as compared with carboplatin-paclitaxel, with respect to progression-free survival in the intention-to-treat population (hazard ratio for progression or death, 0.74; 95% confidence interval [CI], 0.65 to 0.85; P<0.001). In the subgroup of 261 patients who were positive for the epidermal growth factor receptor gene (EGFR) mutation, progression-free survival was significantly longer among those who received gefitinib than among those who received carboplatin-paclitaxel (hazard ratio for progression or death, 0.48; 95% CI, 0.36 to 0.64; P<0.001), whereas in the subgroup of 176 patients who were negative for the mutation, progression-free survival was significantly longer among those who received carboplatin-paclitaxel (hazard ratio for progression or death with gefitinib, 2.85; 95% CI, 2.05 to 3.98; P<0.001). The most common adverse events were rash or acne (in 66.2% of patients) and diarrhea (46.6%) in the gefitinib group and neurotoxic effects (69.9%), neutropenia (67.1%), and alopecia (58.4%) in the carboplatin-paclitaxel group. CONCLUSIONS Gefitinib is superior to carboplatin-paclitaxel as an initial treatment for pulmonary adenocarcinoma among nonsmokers or former light smokers in East Asia. The presence in the tumor of a mutation of the EGFR gene is a strong predictor of a better outcome with gefitinib. (ClinicalTrials.gov number, NCT00322452.)

Osimertinib in Untreated EGFR-Mutated Advanced Non–Small-Cell Lung Cancer

Background Osimertinib is an oral, third‐generation, irreversible epidermal growth factor receptor tyrosine kinase inhibitor (EGFR‐TKI) that selectively inhibits both EGFR‐TKI–sensitizing and EGFR T790M resistance mutations. We compared osimertinib with standard EGFR‐TKIs in patients with previously untreated, EGFR mutation–positive advanced non–small‐cell lung cancer (NSCLC). Methods In this double‐blind, phase 3 trial, we randomly assigned 556 patients with previously untreated, EGFR mutation–positive (exon 19 deletion or L858R) advanced NSCLC in a 1:1 ratio to receive either osimertinib (at a dose of 80 mg once daily) or a standard EGFR‐TKI (gefitinib at a dose of 250 mg once daily or erlotinib at a dose of 150 mg once daily). The primary end point was investigator‐assessed progression‐free survival. Results The median progression‐free survival was significantly longer with osimertinib than with standard EGFR‐TKIs (18.9 months vs. 10.2 months; hazard ratio for disease progression or death, 0.46; 95% confidence interval [CI], 0.37 to 0.57; P<0.001). The objective response rate was similar in the two groups: 80% with osimertinib and 76% with standard EGFR‐TKIs (odds ratio, 1.27; 95% CI, 0.85 to 1.90; P=0.24). The median duration of response was 17.2 months (95% CI, 13.8 to 22.0) with osimertinib versus 8.5 months (95% CI, 7.3 to 9.8) with standard EGFR‐TKIs. Data on overall survival were immature at the interim analysis (25% maturity). The survival rate at 18 months was 83% (95% CI, 78 to 87) with osimertinib and 71% (95% CI, 65 to 76) with standard EGFR‐TKIs (hazard ratio for death, 0.63; 95% CI, 0.45 to 0.88; P=0.007 [nonsignificant in the interim analysis]). Adverse events of grade 3 or higher were less frequent with osimertinib than with standard EGFR‐TKIs (34% vs. 45%). Conclusions Osimertinib showed efficacy superior to that of standard EGFR‐TKIs in the first‐line treatment of EGFR mutation–positive advanced NSCLC, with a similar safety profile and lower rates of serious adverse events. (Funded by AstraZeneca; FLAURA ClinicalTrials.gov number, NCT02296125.)

Cost-effectiveness analysis of cisplatin plus etoposide and carboplatin plus paclitaxel in a phase III randomized trial for non-small cell lung cancer

Aim:  Carboplatin plus paclitaxel is a more costly chemotherapy regimen than cisplatin plus etoposide; however there have been reports of higher efficacy and less toxicity of this regimen. Thus, this study aimed to assess the cost‐effectiveness of these two chemotherapy regimens in advanced non‐small cell lung cancer (NSCLC).

Reliability and validity of the Thai translation (Thai PPS Adult Suandok) of the Palliative Performance Scale (PPSv2)

Purpose: the Thai PPS Adult Suandok tool was translated from the Palliative Performance Scale (PPSv2) and had been used in Chiang Mai, Thailand for several years. Aim: to test the reliability and validity of the Thai translation of PPSv2. Design: a set of 22 palliative cases were used to determine a PPS score on Time-1, and repeated two weeks later as Time-2. A survey questionnaire was also completed for qualitative analysis. Participants: a total of 70 nurses and physicians from Maharaj Nakorn Hospital in Chiang Mai participated. Results: The Time-1 intraclass correlation coefficient (ICC) for absolute agreement is 0.911 (95% CI 0.86–0.96) and for consistency is 0.92 (95% CI 0.87–0.96). The Time-2 ICC for agreement is 0.905 (95% CI 0.85–0.95) and for consistency is 0.912 (95% CI 0.86–0.96). These findings indicate good agreement among participants and also were somewhat higher in the Time-2 re-test phase. Cohen’s kappa score is 0.55, demonstrating a moderate agreement. Thematic analysis from the surveys showed that 91% felt PPS to be a valuable clinical tool overall, with it being ‘very useful’ or ‘useful’ in several areas, including care planning (78% and 20%), disease monitoring (69% and 27%) and prognostication (61% and 31%), respectively. Some respondents noted difficulty in determining appropriate scores in paraplegic patients or those with feeding tubes, while others found the instructions long or difficult. Conclusion: the Thai PPS Adult Suandok translated tool has good inter- and intra-rater reliability and can be used regularly for clinical care.

Outcome of eribulin as a late treatment line for Thai metastatic breast cancer patients

Background We report the safety and efficacy of eribulin as a late treatment line in Thai metastatic breast cancer (MBC) patients. Patients and methods A total of 30 MBC patients treated with eribulin between January 2014 and January 2017 were retrospectively analyzed. The patients were scheduled to receive 1.4 mg/m2 of eribulin on day 1, day 8 and subsequently every 21 days. All patients had previously received at least three chemotherapy regimens including anthracycline and taxane. Response rate and progression-free survival (PFS) were analyzed. Results The median age was 56 years (range, 40–74 years), with a median follow-up time of 5.7 months (range, 0.2–25 months). The overall response rate was 30% (nine patients): four patients had triple-negative breast cancer, three patients had luminal B breast cancer and two patients had luminal A breast cancer. The median PFS was 2.9 months (range, 0.2–14 months). The median number of previous chemotherapy regimens was 4 (range, 3–9). Univariate analysis showed that the number of regimens (four or fewer) prior to eribulin was statistically associated with superior PFS (P = 0.009). Multivariate analysis also showed similar statistical association between number of prior regimens (four or fewer) and better PFS adjusted by age group (≥50 years; hazard ratio = 1.29; 95% CI: 1.0–1.65; P = 0.046). There were no toxic deaths or grade 4 toxicities. Nine (30%) patients had grade 3 anemia toxicities, and the other common toxicities were leukopenia and neutropenia. Four (13%) patients required dose reduction and 16 (53%) patients required dose delay because of toxicities. Conclusion Eribulin is an effective drug for heavily pretreated MBC patients with tolerable toxicities. The benefit was superior in patients who received fewer than four previous chemotherapy regimens.