Discordance in Recommendation Between Next-Generation Sequencing Test Reports and Molecular Tumor Boards in India.

PURPOSE: Accurate understanding of the genomic and transcriptomic data provided by next-generation sequencing (NGS) is essential for the effective utilization of precision oncology. Molecular tumor boards (MTBs) aim to translate the complex data in NGS reports into effective clinical interventions. Often, MTB treatment recommendations differ from those in the NGS reports. In this study, we analyze the discordance between these recommendations and the rationales behind the discordances, in a non-high-income setting, with international input to evaluate the necessity of MTB in clinical practice. METHODS: We collated data from MTB that were virtually hosted in Chennai, India. We included patients with malignancies who had NGS reports on solid tissue or liquid biopsies, and excluded those with incomplete data. MTB forms and NGS reports of each clinical case were analyzed and evaluated for recommendation concordance. Concordance was defined as an agreement between the first recommendation in the MTB forms and the therapeutic recommendations suggested in the NGS report. Discordance was the absence of the said agreement. The rationales for discordance were identified and documented. RESULTS: Seventy MTB reports were analyzed with 49 cases meeting the inclusion criteria. The recommendation discordance was 49% (24 of 49). Discordant recommendations were mainly due to low level of evidence for the drug (75% of cases). CONCLUSION: The discordance between MTB and NGS vendor recommendations highlights the clinical utility of MTB. The educational experiences provided by this initiative are an example of how virtual academic collaborations can enhance patient care and provider education across geographic borders.

Risk factors for the development of triple-negative breast cancer versus non-triple-negative breast cancer: a case-control study.

The risk factors for breast cancer have been defined in several studies but there is deficient data for specific subtypes. We report here the pathological characteristics of a breast cancer cohort and risk factors for patients with triple-negative disease. In this case-control study, a prospective breast cancer cohort was evaluated for demographic, reproductive, obesity-related and other risk factors using a validated questionnaire. Tumors were characterized for routine pathological characteristics and immunohistochemical markers of basal-like breast cancer. Patients with triple-negative breast cancer (TNBC) constituted cases and those with non-TNBC were controls. Odds ratios (OR) were calculated for each risk factor and independent associations were tested in an unconditional logistic regression analysis. Between 2011 and 2014, 1146 patients were recruited, of whom 912 [TNBC 266 (29.1%), non-TNBC 646 (70.9%)] with sufficient pathology material were analysed. Reproductive factors of parity, breastfeeding, age-at-menarche, age at first full-term pregnancy and oral contraceptive use were not significantly associated with TNBC. Higher body mass index (BMI > 24.9 vs ≤ 24.9, OR 0.89, 95%CI 0.63-1.24, p = 0.49) was not significantly associated while lesser waist circumference (> 80 cm vs ≤ 80 cm, OR 0.64, 95%CI 0.45-0.9, p = 0.012) and lower waist-to-hip ratio were significantly associated (> 0.85 vs ≤ 0.85, OR 0.72, 95%CI 0.51-1.0, p = 0.056), with TNBC. History of tobacco use was not significantly associated while lower socio-economic status was borderline associated with TNBC (socio-economic category > 5 versus ≤ 5, OR 0.73, 95%CI 0.50-1.06, p = 0.106). No factor was significant after adjustment for covariates. Central obesity seems to be preferentially associated with non-TNBC, and lower socio-economic status with TNBC in India, while most other conventional risk factors of breast cancer show no significant association with TNBC versus non-TNBC.

Translating the COVID-19 experience in widening the HPV vaccination campaign for cervical cancer in India.

India has proven by the success of COVID vaccination that it has a huge production and distribution capacity, availability of professionally trained medical staff, world renowned digital infrastructure to enrol people, conduct camps and maintain records, and a positive mindset among the people towards vaccination. There is an unmet need to enforce that cervical cancer is a "preventable tragedy," and vaccination is an invaluable way ahead. With this article, we hope to attract attention to translating India's successful COVID-19 vaccination campaign experience to developing the HPV vaccination campaign.

Maintenance therapy for newly diagnosed epithelial ovarian cancer- a review.

Epithelial ovarian cancer (EOC) is the most lethal gynaecological cancer among women worldwide, with the 5-year survival rate ranging between 30 and 40%. Due to the asymptomatic nature of the condition, it is more likely to be diagnosed at an advanced stage, requiring an aggressive therapeutic approach. Cytoreductive surgery (CRS) along with systemic chemotherapy with paclitaxel and carboplatin has been the mainstay of the treatment in the frontline management of EOC. In recent years, neo-adjuvant chemotherapy, followed by interval CRS has become an important strategy for the management of advanced EOC. Due to the high rate of recurrence, the oncology community has begun to shift its focus to molecular-targeted agents and maintenance therapy in the frontline settings. The rationale for maintenance therapy is to delay the progression or relapse of the disease, as long as possible after first-line treatment, irrespective of the amount of residual disease. Tumours with homologous recombination deficiency (HRD) including BReast CAncer gene (BRCA) mutations are found to be sensitive to polyadenosine diphosphate-ribose polymerase (PARP) inhibitors and understanding of HRD status has become important in the frontline setting. PARP inhibitors are reported to provide a significant improvement in progression-free survival and have an acceptable safety profile. PARP inhibitors have also been found to act regardless of BRCA status. Recently, PARP inhibitors as maintenance therapy in the frontline settings showed encouraging results in EOC; however, the results from further trials and survival data from ongoing trials are awaited for understanding the role of this pathway in treatment of EOC. This review discusses an overview of maintenance strategies in newly diagnosed EOC along with considerations for maintenance therapy in EOC with a focus on PARP inhibitors.

Palbociclib and beyond for the treatment of HR + HER2- metastatic breast cancer: an Asian-Pacific perspective and practical management guide on the use of CDK4/6 inhibitors.

Breast cancer is the most frequent cancer amongst women worldwide including in Asia where the incidence rate is rapidly increasing. Even with treatment, around 30% of patients with early breast cancer progress to metastatic disease, with hormone receptor positive (HR+) and human epidermal growth factor receptor 2 negative (HER2-) breast cancer the most common phenotype. First-line endocrine therapy targeting the estrogen receptor signaling pathway provides a median progression-free survival or time to progression of 6-15 months in HR + HER2- metastatic breast cancer. Recently, cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors, combined with endocrine therapy, have achieved more than two years median progression-free survival in HR + HER2- metastatic breast cancer. However, the characteristics of the Asian breast cancer population differ from those of Western populations and need to be considered when selecting a suitable treatment. Breast cancer is diagnosed at a younger age in Asian populations and late stage at presentation is generally more common in low-/middle-income countries than high-income countries. Consequently, the proportion of premenopausal women with metastatic breast cancer is higher in Asian compared with Western populations. While CDK4/6 inhibitors have been approved in the USA (FDA) since 2015, experience with them in Asia is more limited. We review the experience with the CDK4/6 inhibitor palbociclib in Asian patients with HR + HER2- metastatic breast cancer and provide guidance on the use of palbociclib in these patients.

Expert Consensus on Effective Management of Chemotherapy-Induced Nausea and Vomiting: An Indian Perspective.

Chemotherapy-induced nausea and vomiting (CINV) is one of the most common and feared side effects in cancer patients undergoing chemotherapy. Scientific evidence proves its detrimental impact on a patient's quality of life (QoL), treatment compliance, and overall healthcare cost. Despite the CINV-management landscape witnessing a radical shift with the introduction of novel, receptor-targeting antiemetic agents, this side effect remains a chink in the armor of a treating oncologist. Though global guidelines acknowledge patient-specific risk factors and chemotherapeutic agent emetogenic potential in CINV control, a "one-fit-for-all" approach cannot be followed across all geographies. Hence, in a pioneering attempt, India-based oncologists conveyed easily implementable, region-specific, consensus-based statements on CINV prevention and management. These statements resulted from integrating the analysis of scientific evidence and guidelines on CINV by the experts, with their clinical experience. The statements will strengthen decision-making abilities of Indian oncologists/clinicians and help in achieving consistency in CINV prevention and management in the country. Furthermore, this document shall lay the foundation for developing robust Indian guidelines for CINV prevention and control.

Mainstreaming genetic counseling for BRCA testing into oncology clinics - Indian perspective.

BReastCAncer (BRCA) susceptibility genes BRCA1 and BRCA2 are mainly associated with hereditary breast and ovarian cancer (HBOC) syndrome and present an estimated 45%-65% cumulative lifetime risk of developing breast cancer and an 11%-39% risk of ovarian cancer. HBOC is also linked to triple-negative breast cancer (TNBC). BRCA1 mutations in TNBC are observed in 36% of women age <40 years and 27% of women age <50 years. In India, the prevalence of BRCA1/2 mutation varies from 2.9% to 38% among families with genetic predisposition toward hereditary cancers. With HBOC being linked to early-onset breast cancer and increased susceptibility to other cancers, early screening for BRCA mutations has become a pressing need. Though genetic counseling (GC) for BRCA mutation testing is common in most of the developed countries, India still faces several challenges in mainstreaming the same. Many barriers to effective GC for BRCA testing are unique to India. There is a dearth of trained geneticists which puts the pressure on oncologists to give GC for which they neither have the time or training. Presence of multiethnic/linguistic population acts as a major hindrance along the way toward development of robust predictive and effective GC models for BRCA testing. The current review discusses the need and benefits of GC in breast cancer prevention, through BRCA testing, from an Indian perspective. The functional framework of GC and the role of genetic counselors are discussed in detail. In addition, importance of GC training and role of a multidisciplinary team approach for mainstreaming pre- and post-BRCA test GC is highlighted.

Maintenance therapy for recurrent epithelial ovarian cancer: current therapies and future perspectives - a review.

Epithelial ovarian cancer (EOC) is usually diagnosed late at an advanced stage. Though EOC initially responds to treatment, the recurrence rate is pretty high. The efficacy of different targeted therapies reduces with each recurrence. Hence there is need of effective maintenance therapy in recurrent EOC. Recently, polyADP-ribose polymerase (PARP) inhibitors (PARPi) have been approved both for initial treatment of EOC and as its maintenance treatment. PARPi have also been found to act regardless of BRCA status or homologous recombination (HR) deficiency. Several trials testing PARPi early in maintenance therapy are in progress and their results will shed light on the optimal timing of maintenance therapy that gives the most benefit with least toxicity. Right patient selection for maintenance treatment is also a challenge. Hence, though PARPi are emerging as a promising maintenance treatment in recurrent EOC with prolongation of progression free survival (PFS), results from further trials and overall survival (OS) data from current trials are awaited to fulfill the gaps in understanding the role of this pathway in treatment of EOC. This review discusses the current therapies for EOC, challenges in the treatment of recurrent EOC, recent developments and trials in recurrent EOC maintenance with special focus on PARPi and future perspectives.

Evidence for the association of Epstein-Barr Virus in breast cancer in Indian patients using in-situ hybridization technique.

Epstein-Barr Virus (EBV) is etiologically linked to Burkitt lymphoma (BL), nasopharyngeal carcinoma, post-transplant lymphomas, Hodgkin disease, and possibly other tumors. However, the association of oncogenic EBV with breast carcinoma (BC) is still controversial and a matter of debate. We aimed to study the presence of EBV genome in BC cases in Indian patients and its association with the clinicopathological features. The formalin fixed paraffin embedded tissues from 83 women with primary invasive BC were studied for the presence of EBV by in-situ hybridization (ISH) technique for Epstein-Barr Virus Encoded RNA (EBER) with appropriate controls. Correlation of EBER-ISH positivity with clinicopathological features was performed using Fisher exact test and P<.05 was considered as significant. Eighty-three BC cases were comprised of 47 (56.5%) triple negative breast cancers (TNBC), 17 (20.5%) hormone positive and 19 (22.9%) HER2 positive cases. Of 83 cases, 25 cases (30.1%) were positive for EBER-ISH test. The positivity was restricted to the tumor cells and not seen in the surrounding breast lobules. EBER-ISH positivity was statistically associated with larger tumor size (52.6% in >5 cm tumors vs 19.3% in ≤5 cm; P=.014) and with TNBCs (21/47 [44.7%] in TNBCs vs 4/36 [11.1%] in non-TNBCs; P=.001). A possible causal association of EBV in BC cases in Indian patients is suggested by high frequency of EBER-ISH positivity noted in our study. This might have therapeutic significance because of the possible role of EBV specific cytotoxic T cells in targeting EBV associated tumor cells and can be considered as a potential targeted therapy. To the best of our knowledge, this is the first study from India to address this issue using EBER-ISH technique.

A Comparison of Clinical Features, Pathology and Outcomes in Various Subtypes of Breast Cancer in Indian Women.

BACKGROUND: Breast cancer is often classified into subtypes using immunohistochemical markers. These subtypes have distinct biological behaviour. This study was conducted with the aim of estimating the distribution of various subtypes of breast cancer in Indian population based on immunohistochemistry markers and to determine the clinical features, pathology and outcomes of these subtypes of breast cancer. MATERIALS AND METHODS: A retrospective study was undertaken and all patients of breast cancer over a 5 year period were included. These patients were divided into 4 subgroups depending on the presence or absence of immunohistochemical markers: i) Luminal A (ER/PR+, Her 2 neu-); ii) Luminal B (ER/PR+, Her 2 neu+); iii) Her 2 enriched (ER-/PR-, Her 2 neu+) and; iv) Triple negative (ER-, PR-, Her2 neu-). Clinical and pathological features and survival were compared between patients in the 4 subgroups. RESULTS: Luminal A subgroup had majority of patients (43.8%). Patients in Luminal B, Her 2 enriched, and Triple negative subgroups were 14.8%, 16.1% and 25.3%. Median follow-up of patients was for 34 months. Luminal A subgroup patients were more likely to be postmenopausal and have smaller and lower grade (I/II) tumours with better survival (OS-91.06%). Patients in the Triple negative subgroup were more likely to be premenopausal (p-value 0.036, odds ratio 0.611, CI 0.394-0.949), have larger and higher grade (III) tumours with worse overall survival (OS-88.46%, odds ratio 1.32, 95%CI 0.602-2.39). Her 2 enriched group patients had bad prognostic features like larger size of tumour and higher grade of tumour and worst survival among all the subgroups (OS-85.07%, odds ratio 1.78, 95% CI 0.767-4.163). However, these outcomes were not statistically significant for the subgroups. CONCLUSION: A retrospective study was undertaken of breast cancer patients in India, according to subtypes based on immunohistochemistry. Luminal A had prognostic features and survival which was better as compared to other subgroups (Luminal B, Her 2 enriched and Triple negative). Incidence of patients with Triple negative breast cancer was higher in the premenopausal period. Patients with Her 2 enriched breast cancer had the worst survival among all the subgroups.

Nimotuzumab plus chemotherapy versus chemotherapy alone in advanced non-small-cell lung cancer: a multicenter, randomized, open-label Phase II study.

BACKGROUND: The purpose of this study was to evaluate the safety and efficacy of nimotuzumab in combination with chemotherapy (docetaxel and carboplatin) versus chemotherapy alone in patients with stage IIIB/IV non-small-cell lung cancer. METHODS: This multicenter, open-label, Phase II study randomized 110 patients to receive nimotuzumab plus chemotherapy (nimotuzumab group) or chemotherapy alone (control group), and comprised concomitant, maintenance, and follow-up phases. Nimotuzumab 200 mg was administered once weekly for 13 weeks during the first two phases with four cycles of chemotherapy and docetaxel 75 mg/m(2) and carboplatin (area under the curve 5 mg/mL*min) every 3 weeks for a maximum of four cycles during the concomitant phase. The primary endpoint was objective response rate (sum of complete response and partial response). Secondary endpoints, ie, overall survival and progression-free survival, were estimated using the Kaplan-Meier method. Efficacy was evaluated on the intent-to-treat and efficacy-evaluable sets. Safety was assessed from adverse event and serious adverse event data. RESULTS: The objective response rate was significantly higher in the nimotuzumab group than in the control group in the intent-to-treat population (54% versus 34.5%; P=0.04). A complete response and partial response were achieved in 3.6% and 50% of patients, respectively, in the nimotuzumab group, and in 4% and 30.9% of patients, respectively, in the control group. No significant differences in median progression-free survival and overall survival were observed. Safety profiles were comparable between the two groups. CONCLUSION: Nimotuzumab plus chemotherapy significantly improved the objective response rate as compared with chemotherapy alone. The combination was safe and well tolerated in patients with stage IIIB/IV non-small-cell lung cancer.

Neoadjuvant doxorubicin/cyclophosphamide followed by ixabepilone or paclitaxel in early stage breast cancer and evaluation of ßIII-tubulin expression as a predictive marker.

BACKGROUND: This randomized phase II trial was designed to compare the rate of pathologic complete response (pCR) induced by neoadjuvant cyclophosphamide plus doxorubicin (AC) followed by ixabepilone or paclitaxel in women with early stage breast cancer (BC). Expression of ßIII-tubulin as a predictive marker was also evaluated. PATIENTS AND METHODS: Women with untreated, histologically confirmed primary invasive breast adenocarcinoma received four cycles of AC followed by 1:1 randomization to either ixabepilone 40 mg/m2 (3-hour infusion) every 3 weeks for four cycles (n = 148) or weekly paclitaxel 80 mg/m2 (1-hour infusion) for 12 weeks (n = 147). All patients underwent a core needle biopsy of the primary cancer for molecular marker analysis prior to chemotherapy. ßIII-Tubulin expression was assessed using immunohistochemistry. RESULTS: There was no significant difference in the rate of pCR in the ixabepilone treatment arm (24.3%; 90% confidence interval [CI], 18.6-30.8) and the paclitaxel treatment arm (25.2%; 90% CI, 19.4-31.7). ßIII-Tubulin-positive patients obtained higher pCR rates compared with ßIII-tubulin-negative patients in both treatment arms; however, ßIII-tubulin expression was not significantly associated with a differential response to ixabepilone or paclitaxel. The safety profiles of both regimens were generally similar, although neutropenia occurred more frequently in the ixabepilone arm (grade 3/4: 41.3% vs. 8.4%). The most common nonhematologic toxicity was peripheral neuropathy. CONCLUSIONS: Neoadjuvant treatment of early stage BC with AC followed by ixabepilone every 3 weeks or weekly paclitaxel was well tolerated with no significant difference in efficacy. Higher response rates were observed among ßIII-tubulin-positive patients.

A multicenter phase II randomized study of Cremophor-free polymeric nanoparticle formulation of paclitaxel in women with locally advanced and/or metastatic breast cancer after failure of anthracycline.

AIMS: Paclitaxel is extensively used in the treatment of advanced carcinomas of the breast, ovary and non-small cell lung cancer. In clinical use it is formulated in the non-ionic surfactant polyethoxylated castor oil (Cremophor) and dehydrated alcohol to enhance drug solubility. Cremophor adds to toxic effects of paclitaxel by producing or contributing to the well-described hypersensitivity reactions that commonly occur during its infusion, affecting a large number of patients. This randomized trial was conducted to evaluate efficacy and safety of novel nanoparticle-based paclitaxel in the treatment of patients with advanced breast cancer. METHOD: Patients were randomized to receive either nanoparticle paclitaxel (NP) 300 mg/m(2) , (NP300) or NP220 mg/m(2) or Cremophor paclitaxel 175 mg/m(2) (CP 175). NP was administered as a 1-h infusion without premedication and CP as a 3-h infusion with premedication every 3 weeks. RESULTS: In total, 194 patients who had been administered at least one dose were included for safety analysis and 170 patients who completed at least two cycles of therapy were analyzed for efficacy. NP showed an overall response rate (complete response + partial response) of 40% in the NP220 and NP300 arms as compared to 31% in the CP arm. The incidence of neutropenia (all grades) was lowest in the NP220 arm (39.4%) compared to the NP300 (55%) and CP arm (50%). CONCLUSION: NP is well tolerated and can be safely administered without any premedication in comparison to conventional paclitaxel, which requires the use of premedication before administration. NP demonstrates promising efficacy with a favorable safety profile.

A phase 2 study of sequential neoadjuvant chemotherapy with gemcitabine and doxorubicin followed by gemcitabine and cisplatin in patients with large or locally advanced operable breast cancer: results from long-term follow-up.

BACKGROUND: Neoadjuvant chemotherapy (NACT) is being increasingly used for patients with large-size operable breast cancer. This phase 2 study of sequential NACT with gemcitabine and doxorubicin (Gem + Dox) followed by gemcitabine and cisplatin (Gem + Cis) was conducted in women with large or locally advanced breast cancer. The objectives were to evaluate the pathological complete response (pCR) rate, toxicity, pathological and genetic markers predicting response, the proportion of patients undergoing breast conservation surgery, progression-free survival (PFS) and overall survival (OS) after 5 years, and time to treatment failure (TtTF). In this manuscript, we report the long-term OS, PFS, and TtTF results. METHODS: Female patients aged at least 18 years with large T2 (at least 3 cm) or locally advanced (T3, T4, or N2) breast carcinoma were included. Treatment consisted of 4 cycles of Gem + Dox (gemcitabine 1,200 mg/m(2) on days 1 and 8 plus doxorubicin 60 mg/m(2) on day 1 of each 21-day cycle), followed by 4 cycles of Gem + Cis (gemcitabine 1,000 mg/m(2) on days 1 and 8 plus cisplatin 70 mg/m(2) on day 1 of each 21-day cycle), and then surgery. RESULTS: Sixty-five patients were enrolled. The pCR rate was 20%. The 5-year OS probability was 71% (95% CI 56-82%), and the 4-year PFS and TtTF probabilities were 63% (95% CI 48-74%) and 45% (95% CI 32-57%), respectively. CONCLUSIONS: NACT with Gem + Dox followed by Gem + Cis was efficacious in patients with operable breast cancer.

mTOR inhibition in management of advanced breast cancer.

The mTOR pathway is becoming increasingly important in several cancers including breast cancer. This review will focus on the role of its inhibition in the management of advanced breast cancer.

Randomized, double-blind, placebo-controlled phase II study of single-agent oral talactoferrin in patients with locally advanced or metastatic non-small-cell lung cancer that progressed after chemotherapy.

PURPOSE: To investigate the activity and safety of oral talactoferrin (TLF) in patients with stages IIIB to IV non-small-cell lung cancer (NSCLC) for whom one or two prior lines of systemic anticancer therapy had failed. PATIENTS AND METHODS: Patients (n = 100) were randomly assigned to receive either oral TLF (1.5 g in 15 mL phosphate-based buffer) or placebo (15 mL phosphate-based buffer) twice per day in addition to supportive care. Oral TLF or placebo was administered for a maximum of three 14-week cycles with dosing for 12 consecutive weeks followed by 2 weeks off. The primary objective was overall survival (OS) in the intent-to-treat (ITT) patient population. Secondary objectives included progression-free survival (PFS), disease control rate (DCR), and safety. RESULTS: TLF was associated with improvement in OS in the ITT patient population, meeting the protocol-specified level of significance of a one-tailed P = .05. Compared with the placebo group, median OS increased by 65% in the TLF group (3.7 to 6.1 months; hazard ratio, 0.68; 90% CI, 0.47 to 0.98; P = .04 with one-tailed log-rank test). Supportive trends were also observed for PFS and DCR. TLF was well tolerated and, generally, there were fewer adverse events (AEs) and grade ≥ 3 AEs reported in the TLF arm. AEs were consistent with those expected in late-stage NSCLC. CONCLUSION: TLF demonstrated an apparent improvement in OS in patients with stages IIIB to IV NSCLC for whom one or two prior lines of systemic anticancer therapy had failed and was well tolerated. These results should be confirmed in a global phase III trial.

A randomized, double-blind, placebo-controlled, phase II study of oral talactoferrin in combination with carboplatin and paclitaxel in previously untreated locally advanced or metastatic non-small cell lung cancer.

INTRODUCTION: The aim of the study is to investigate the activity and safety of oral talactoferrin (TLF) plus carboplatin and paclitaxel (C/P) in patients with previously untreated stage IIIB/IV non-small cell lung cancer. METHODS: Patients (n = 110) were randomly assigned to receive C/P plus either TLF (C/P/T) or placebo (C/P/P). The primary objective of this exploratory study was assessment of confirmed response rate (RR) in the prospectively defined evaluable population with a one-tailed p = 0.05. Secondary objectives included assessment of progression-free survival (PFS), duration of response, overall survival (OS), and safety. RESULTS: The trial met the primary end point of improvement in confirmed RR in the prospectively defined evaluable population. Compared with the C/P/P group, RR increased in the C/P/T group by 18% (29-47%; p = 0.05) and 15% (27-42%; p = 0.08) in the evaluable and intent-to-treat populations, respectively. Compared with the C/P/P group, the C/P/T group had a longer median PFS (4.2 versus 7.0 months), OS (8.5 versus 10.4 months), and duration of response (5.5 versus 7.6 months), although the differences were not statistically significant. Adverse events (AEs) were consistent with C/P therapy. There were fewer total AEs (472 versus 569; two-tailed p = 0.003) and grade 3/4 AEs (78 versus 105; p = 0.05) in the C/P/T group compared with the C/P/P group. CONCLUSION: TLF, in combination with C/P, demonstrated an apparent improvement in RR, PFS, and OS in patients with previously untreated stage IIIB/IV non-small cell lung cancer and appears to enhance activity without significant additional toxicity. These results need to be confirmed in a phase III trial.

Gemcitabine plus Paclitaxel versus Paclitaxel monotherapy in patients with metastatic breast cancer and prior anthracycline treatment.

PURPOSE: The objective of this phase III global study was to compare the efficacy of gemcitabine plus paclitaxel (GT) versus paclitaxel in patients with advanced breast cancer. It was designed as a pivotal study for the approval of G for a breast cancer treatment indication. PATIENTS AND METHODS: Patients who relapsed after adjuvant anthracyclines were randomly assigned to gemcitabine,1,250 mg/m(2) days 1 and 8 plus paclitaxel, 175 mg/m(2) on day 1; or, to paclitaxel at same dose on day 1 (both arms administered every 21 days, unblinded). The primary end point was overall survival (OS) and secondary end points were time to progression (TTP), response rate (RR), progression-free survival, response duration, and toxicity. This final OS analysis was planned at 380 deaths. RESULTS: A total of 266 patients were randomly assigned to GT and 263 to paclitaxel. Median survival on GT was 18.6 months versus 15.8 months on paclitaxel (log-rank P = . 0489), with an adjusted Cox hazard ratio of 0.78 (95% CI, 0.64 to 0.96; P = .0187). The TTP was longer (6.14 v 3.98 months; log-rank P = .0002) and the RR was better (41.4% v 26.2%; P = .0002) on GT. There was more grade 3 to 4 neutropenia on GT and grade 2 to 4 fatigue and neuropathy were slightly more prevalent on GT. CONCLUSION: This phase III study documents a role for gemcitabine in advanced breast cancer after anthracycline-based adjuvant therapy. The results establish GT as a reasonable choice for women who require cytoreduction with manageable toxicities and validate ongoing testing of GT in the adjuvant setting.