Dr. Sunil Chopade, an attendee at the American Society of Clinical Oncology (ASCO) 2019 Annual Meeting breaks down the key findings of major trials in lung, gastrointestinal, and breast cancer, adding key takeaways for Indian Oncologists.

Lung Cancer

gef vs gef+C study

Dr. Vanita Noronha from Tata Memorial Hospital, Mumbai gave the oral presentation at ASCO 2019 on the combination of gefitinib (gef) with pemetrexed and carboplatin (C) in the first line treatment of advanced adenocarcinoma of lung, harbouring EGFR sensitising mutation (exon 19, 21 or 18) with performance status (PS) 0 to 2.

Patients were randomised to gefitinib 250 mg orally daily (gef) or gefitinib 250 mg orally daily with pemetrexed 500 mg/m² IV and carboplatin AUC 5 IV every 3 weeks for 4 cycles, followed by maintenance pemetrexed 500 mg/m² IV every 3 weeks (gef+C). Restaging was every 2 to 3 months; therapy continued until progression or intolerable toxicity. Primary end point was progression-free survival (PFS).

1. Median follow-up in surviving patients was 17 months. Radiologic response rates were 81% and 69% in gef+C and gef respectively, P = 0.012.
2. Estimated median PFS was significantly longer with gef+C than gef (16 months, [95% CI, 13.7 to 18.3] vs. 8 months [95% CI, 7.1 to 8.9]; hazard ratio for disease progression or death, 0.5; 95% CI, 0.39 to 0.65; P < 0.001).
3. Estimated median OS was significantly longer with gef+C than gef (not reached vs. 18 months [95% CI, 14.28 to 21.72]; hazard ratio for death, 0.45; 95% CI, 0.31 to 0.66; P < 0.001).
4. Clinically relevant ≥ grade 3 toxicities occurred in 51% and 25% of patients in gef+C and gef arms respectively, P < 0.001.

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ECOG-ACRIN 5508 trial

Dr. Suresh Ramalingam, on behalf of ECOG-ACRIN group presented their work on maintenance therapy for advanced non-squamous NSCLC.

Patients with advanced non-squamous NSCLC, no prior systemic therapy, and ECOG performance status 0/1 were treated with carboplatin (AUC = 6), paclitaxel (200 mg/m²) and bevacizumab (15 mg/Kg) every 3 weeks for up to 4 cycles (step 1).

Patients with CR/PR/SD after 4 cycles were then randomized 1:1:1 to maintenance therapy with bevacizumab (15 mg/Kg), pemetrexed (500 mg/m²) or the combination of the two agents every 3 weeks until disease progression (step 2). The primary endpoint was overall survival.

The overall survival in bevacizumab alone arm was 14.4 months, pemetrexed alone 15.9 months and combination of two resulted in OS of 16.4 months, HR 0.90 (0.73, 1.12) (P=0.28).

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Gastrointestinal Cancer

Phase III POLO trial

Dr. Hedy L. Kindler from University of Chicago presented her trial in patients of metastatic pancreatic cancer who were stable on platinum-based chemotherapy, and who were randomized to olaparib or placebo.

They found that patients given olaparib had a median progression-free survival (PFS) of 7.4 months vs 3.8 months with placebo, equating to a 47% reduction in the risk of disease progression or death. An objective response was seen in more than twice as many olaparib patients than in those given placebo, at a median duration of response of over 2 years with the oral medication.

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TRIBE2 study

Dr. Chiara Cremolini from Italy presented updated results of TRIBE2 trial. In the phase III TRIBE study , FOLFOXIRI/bev significantly improved Response Rate (RR), PFS and OS when compared with FOLFIRI/bev as initial treatment of mCRC.

However, the actual advantage by the triplet could be lower when compared with a pre-planned sequential strategy of doublets (FOLFOX, FOLFIRI). A pre-planned interim analysis showed a significant advantage for arm B in terms of PFS2, primary endpoint of the study, defined as the time from randomization to PD on any treatment given after first PD or death (PD2).

This study showed a significant advantage by upfront FOLFOXIRI/bev in terms of:

• PFS2 (19.1 vs 16.4 mos, p<0.001)
• RR (62% vs 50%, OR 1.61, p=0.002)
• 1st-PFS (12.0 vs 9.8 mos, p<0.001)

A significant OS benefit for patients in arm B was also observed (27.6 vs 22.6 mos, HR: 0.81, 95%CI: 0.67-0.98, p=0.033).

Upfront FOLFOXIRI/bev followed by the pre-planned reintroduction of the same agents after PD provided a statistically significant and clinically relevant PFS2 and OS benefit when compared with the pre-planned sequential administration of FOLFOX/bev and FOLFIRI/bev in unresectable mCRC patients. A median OS of 27.6 months was reached despite the high percentage of patients with poor prognostic features.

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Breast Cancer

Phase III MONALEESA-7 trial

Dr. Sara Hurvitz from Los Angeles presented the overall survival (OS) results of MONALEESA-7. This is the first dedicated trial of endocrine therapy (ET) ± a cyclin-dependent kinase 4/6 (CDK4/6) inhibitor in premenopausal patients with hormone receptor–positive (HR+)/HER2− Advanced Breast Cancer (ABC).

Estimated OS rates with Ribociclib + ET vs Placebo + ET at 42 mo were 70.2% vs 46.0%, respectively. In patients who received an Non Steroidal Aromatase Inhibitor, Ribociclib + ET demonstrated a consistent OS improvement vs Placebo + ET (HR, 0.699 [95% CI, 0.50-0.98]).

Ribociclib + ET demonstrated a clinically and statistically significant longer OS than ET alone in premenopausal pts with HR+/HER2− ABC. This is the first time that a CDK4/6 inhibitor or any targeted agent + ET has demonstrated significantly longer OS vs ET alone as initial endocrine-based therapy.

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Phase III study of GIM

Patients with hormone receptor–positive early-stage breast cancer remain at high risk of late recurrence beyond the first 5 years after diagnosis. It is known that extended endocrine therapy with an aromatase inhibitor after initial 5 years of tamoxifen improves their disease-free survival. However, it remains controversial the benefit of extended endocrine therapy in patients that receive aromatase inhibitor in the first 5 years.

The GIM4 trial addressed this question and showed that extended adjuvant aromatase inhibitor with letrozole (Femara) after 5 years of sequential tamoxifen plus aromatase inhibitor improves disease-free survival. The GIM4 was a prospective randomised multicenter trial in Italy. From August 2005 to May 2010, 2065 patients were randomised to receive either 2-3 years or 5 years of letrozole.

Disclaimer- The views and opinions expressed in this article are those of the author's and do not necessarily reflect the official policy or position of M3 India.

The author, Dr. Sunil Chopade is a Medical Oncologist from Mumbai. His areas of interest include thoracic, gastrointestinal, and breast malignancies.